A Phase 1b/2 Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors
Phase: PHASE1
Conditions: Colorectal Cancer, Pancreatic Cancer
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 1b/2 Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in 
Patients with Advanced Solid Tumors 
 
NCT Number: NCT03184870 
Document Date (Date in which document was last revised): December 5, 2019 

Page:
1
Protocol Number:
CV202103
IND Number:
135,074
EX-US
Non-IND
EUDRACT Number:
2017-001725-40
Date:
11-May-2017
Revised Date
05-Dec-2019
Clinical Protocol CV202103
A Phase 1b/2 Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in
Patients with Advanced Solid Tumors
Short Title:
A Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in Patients with 
Advanced Solid Tumors
Revised Protocol 06
Incorporates Administrative Letter 05
3401 Princeton Pike
Lawrenceville, NJ 08648
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International:
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
2
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised Protocol 06
05-Dec-2019
The following key changes were made:
•
Closed enrollment in Cohort 4 of Part 2.
•
Removed stratification from the protocol.
•
Revised time that women of childbearing potential must 
follow contraception instructions to duration of study 
therapy plus 10 months.
Administrative Letter 05
16-Oct-2019
Updated study personnel.
Administrative Letter 04
07-Jun-2019
Updated study personnel.
Revised Protocol 05
12-Dec-2018
Revised protocol incorporates changes described in the table of 
Summary of Key Changes for Revised Protocol 05.
Revised Protocol 04
12-Jul-2018
Revised protocol incorporates changes described in the table of 
Summary of Key Changes for Revised Protocol 04.
Administrative Letter 03
27-Jun-2018
Clarify that the peripheral blood mononuclear cells (PBMC) 
sample collections in Table 9.8-2, Biomarker Sampling 
Schedule - Part 2, will be whole blood sample collections.
Administrative Letter 02
24-May-2018
Change a typographical error on the title page and page footer 
throughout the protocol. The Revise Date of the Revised 
Protocol 03 is 07-May-2018, not 07-May-2017.
Revised Protocol 03
07-May-2018
Revised protocol incorporates changes described in the table of 
Summary of Key Changes for Revised Protocol 03.
Revised Protocol 02
11-Sep-2017
Revised protocol incorporates changes described in the table of 
Summary of Key Changes in Appendix 13.
Revised Protocol 01
28-Jun-2017
Revised protocol incorporates changes described in the table of 
Summary of Key Changes in Appendix 13.
Administrative Letter 01
20-Jun-2017
1.
Remove a typographical error in the nivolumab treatment 
schedule for Day 28 in Table 2-4.
2.
Reformat the list of study inclusion criteria. 
3.
Include serum testing for hepatitis C antibody to the list of 
clinical laboratory assessments.
4.
Remove PBMC sample collections from the biomarker 
sample schedule. Simplify the biomarker sample schedule 
by aligning the tumor sample collection with the 
on-treatment procedural outlines for Arms A, B, C, and D.
Original Protocol
11-May-2017
Not applicable
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
OVERALL RATIONALE FOR REVISED PROTOCOL 06:
This protocol has been revised to 1) close enrollment in Cohort 4 of Part 2 (BMS 813160 + 
nivolumab in second line [2L] pancreatic cancer) due to futility based on a predetermined analysis, 
2) remove stratification from the randomization process to align with the IRT system, 3) allow 
biosimilars of bevacizumab to be added to 2L FOLFIRI treatment to align protocol treatment with 
current standard of care, and 4) increase the duration of contraception following study treatment 
to align with current BMS and Health Authority guidelines. Additional key changes included in 
this revised protocol are summarized in the table below.
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number
& Title
Description of Change
Brief Rationale
Synopsis
Synopsis was updated.
Synopsis was updated to reflect the 
changes in the body of the protocol as 
summarized below.
Table 2-2 Baseline for Cross-
Over Procedural Outline - Cohort 
1c to Cohort 5 - Cohort 3c to 
Cohort 4 (Closed per Revised 
Protocol 06) - Part 2 
(CV202103); Figure 5.1-2 Study 
Design Schematic (Part 2) -
Combination Therapy Expansion; 
Section 5.1.3 Treatment Period 
(Part 2); Section 5.1.4 Treatment 
Period (Parts 1 and 2); Section 
5.1.5.1 Safety Follow-up; Section 
5.4.3 Rationale  for 2-Stage 
Design in Cohorts in Arm C; 
Section 5.4.3.1 Rationale for 
Closing Cohort 4; Section 6.1 
Inclusion Criteria ii) 9); Section 
10.1 Sample Size Determination; 
Table 10.1-1 Example of Design 
Characteristics
Closed enrollment in Cohort 4 of 
Part 2 (2L pancreatic cancer; 
BMS-813160 + nivolumab).
Participants in Cohort 3c that progress 
on treatment can no longer cross over 
to Cohort 4.
Cohort 7 (BMS-813160 monotherapy; 
2L pancreatic cancer) will not open 
for enrollment due to lack of clinical 
response in Cohort 4.
Following a predetermined analysis at 
Stage 1 for Part 2 Cohort 4, this 
BMS-813160 in combination with 
nivolumab in 2L pancreatic cancer 
cohort was closed due to futility. 
Discontinuation is not due to safety 
concerns. 
As such, participants who progress on 
1L chemotherapy in Part 2 Cohort 3c 
can no longer cross over to Cohort 4. 
In addition, Cohort 7 will not open for 
enrollment because predetermined 
criteria (ORR ≈15% or durable 
responses) in Cohort 4 were not met. 
Table 2-3: On treatment 
Procedural Outline - BMS-
813160/FOLFIRI (Arm A) - Parts 
1 and 2 (CV202103); Section 
3.1.3 Rationale for the 
Chemotherapy Regimens in Arms 
A and B; Section 5.1.3 Treatment 
Period (Part 2); Section 5.5.3 
Rationale for Dose Selection of 
FOLFIRI; Section 7.1 Treatments 
Administered
Indicated that biosimilars of 
bevacizumab can be added to 2L 
FOLFIRI treatment if appropriate.
Modified to align with current 
standards of care.
Section 3.2.1.4 Clinical Safety of 
BMS-813160; Section 3.3 
Benefit/Risk Assessment
Updated safety data for Study 
CV202103.
Updated to align with updated 
Investigator Brochure (IB).
Revised Protocol No.: 06
Date: 05-Dec-2019
4
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number
& Title
Description of Change
Brief Rationale
Figure 5.1-1 Study Design 
Schematic (Part 1); Section 5.5.2  
Rationale for Testing Lower Dose 
of BMS-813160
Indicated for Arm C that the 
BMS-813160 150-mg and 300-mg QD 
dose assignments are only allowed for 
participants with colorectal cancer.
Added to clarify eligibility criteria. 
Section 5.4.4 Rationale for 
Control Arms; Section 7.2 
Method of Treatment 
Assignment; Section 10.3.1 
Efficacy Analyses;
Stratification was removed from the 
protocol.
BMS discovered that the stratification 
of subjects was not occurring in the 
IRT system in Study CV202103. The 
lack of stratification does not have any 
effect on patient safety. As this study 
is powered to estimate an efficacy 
signal with moderate confidence, not 
to establish efficacy with high 
precision as in a registrational study, 
the absence of a single stratification 
factor per randomization is not 
expected to affect the scientific value 
of the study. The appropriate data are 
being collected and a retrospective 
analysis of both tumor sidedness and 
prior therapies will be performed.
Section 6.1 Inclusion Criteria 
3)d)i)
Amended criterion to allow up to 15% 
of treated participants per arm without
confirmation of adequate tissue in 
mandatory pre-treatment biopsy.
Previous version of protocol allowed 
5 participants per cohort, which was 
not practical as randomization occurs
after quality control confirmation. 
15% per arm is in line with the 
original intent of the protocol. 
Section 6.1 Inclusion Criteria 4)d)
Section 6.1 Inclusion Criteria 4)e)
Women of childbearing potential 
(WOCBP) must follow contraception 
instructions for duration of study 
therapy plus 10 months.
Males who are sexually active with 
WOCBP must follow contraception 
instructions for duration of study 
therapy plus 7 months.
Updated per BMS guidelines and to
align with the new FDA guidelines 
regarding required contraception 
duration timeframe for agents with 
reproductive toxicity in female 
participants (5 half-lives plus 
6 months).
Section 6.2 Exclusion Criteria 
4)d); Section 7.7.1 Prohibited 
and/or Restricted Treatments
Added language clarifying that Class 
1A and 1C antiarrhythmics and 
tricyclic antidepressants are prohibited 
concomitant therapies, and that 
caution is warranted with use of Class 
1B antiarrhythmics and methadone.
Added to clarify prohibited and 
restricted medications associated with 
sodium channel blockade.
Section 7.4.2 Management 
Algorithms for Immuno-oncology 
Agents; 
Added myocarditis to list of adverse 
events with management algorithms in 
Appendix 6-2.
Aligned with contents of Appendix 
6-2.
Section 9.2.5 Pregnancy
Extended the duration of 
contraception.
Updated per BMS protocol standards.
Revised Protocol No.: 06
Date: 05-Dec-2019
5
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number
& Title
Description of Change
Brief Rationale
Appendix 2 Study Governance 
Considerations
Updated language around reporting 
potential serious breaches and added 
section on Scientific Publications.
Updated per BMS protocol standards
Appendix 4 Women of 
Childbearing Potential 
Definitions and Methods of 
Contraception
Clarified descriptions of contraceptive 
methods.
Updated per BMS protocol standards.
Appendix 6-2 Management 
Algorithms
Added management algorithm for 
myocarditis.
Updated per BMS protocol standards
All
Minor formatting and typographical
corrections.
Revised Protocol No.: 06
Date: 05-Dec-2019
6
7.0
Approved
930114148
7.0
v
Approved
1.0
v

7$%/(2)&217(176


7,7/(3$*(

'2&80(17+,6725<

29(5$//5$7,21$/()255(9,6('35272&2/

6800$5<2).(<&+$1*(6)255(9,6('35272&2/

7$%/(2)&217(176

6<1236,6

6&+('8/(2)$&7,9,7,(6

,1752'8&7,21

6WXG\5DWLRQDOH

5DWLRQDOHIRU,QKLELWLQJ&&5LQ&DQFHU

5DWLRQDOHIRU6HOHFWLQJ3DWLHQWVZLWK3DQFUHDWLFDQG&RORUHFWDO&DQFHUV
DQG&RPELQLQJZLWK&KHPRWKHUDS\

5DWLRQDOHIRUWKH&KHPRWKHUDS\5HJLPHQVLQ$UPV$DQG%

5DWLRQDOHIRU6HOHFWLQJ/&5&LQ3DUW$UP$

5DWLRQDOHIRU&RPELQLQJ%06ZLWK1LYROXPDELQ3DWLHQWVZLWK
$GYDQFHG3DQFUHDWLFDQG&RORUHFWDO&DQFHUVLQ$UP&

5DWLRQDOHIRU7HVWLQJ/RZHU'RVHRI%06

5DWLRQDOHIRU7HVWLQJ%06LQ&RPELQDWLRQZLWK1LYROXPDE
*HPFLWDELQHDQG1DE3DFOLWD[HO

5DWLRQDOHIRU([SORULQJ0RQRWKHUDS\LQ$UP'

%DFNJURXQG

%06

1RQFOLQLFDO3KDUPDFRORJ\RI%06

1RQFOLQLFDO3KDUPDFRNLQHWLFVDQG0HWDEROLVPRI%06

&OLQLFDO3KDUPDFRNLQHWLFVRI%06

&OLQLFDO6DIHW\RI%06

1LYROXPDE

1RQFOLQLFDO3KDUPDFRNLQHWLFVDQG0HWDEROLVPRI1LYROXPDE

&OLQLFDO3KDUPDFRNLQHWLFVRI1LYROXPDE

%HQHILW5LVN$VVHVVPHQW

6DIHW\0RQLWRULQJRQ6WXG\7UHDWPHQW

2%-(&7,9(6$1'(1'32,176

678'<'(6,*1

2YHUDOO'HVLJQ

6FUHHQLQJ3HULRG

7UHDWPHQW3HULRG3DUW

7UHDWPHQW3HULRG3DUW

7UHDWPHQW3HULRG3DUWVDQG

)ROORZXS3HULRG3DUWVDQG

6DIHW\)ROORZXS

6XUYLYDO)ROORZXS

'DWD0RQLWRULQJ&RPPLWWHHDQG2WKHU([WHUQDO&RPPLWWHHV

1XPEHURI3DUWLFLSDQWV

(QGRI6WXG\'HILQLWLRQ










































Clinical Protocol
BMS-813160
CV202103
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
7
7.0
Approved
930114148
7.0
v
Approved
1.0
v

6FLHQWLILF5DWLRQDOHIRU6WXG\'HVLJQ

5DWLRQDOHIRU0RQRWKHUDS\/HDGLQ3DUW

5DWLRQDOHIRU7HVWLQJ'LIIHUHQW'RVHVRI%06LQ3DUW

5DWLRQDOHIRU6WDJH'HVLJQLQ&RKRUWVLQ$UP&

5DWLRQDOHIRU&ORVLQJ&RKRUW

5DWLRQDOHIRU&RQWURO$UPV

5DWLRQDOHIRU0$7(UHQDO%LRPDUNHU6DPSOH&ROOHFWLRQ

5DWLRQDOHIRU8VLQJ%067DEOHW

5DWLRQDOHIRU'RVH

5DWLRQDOHIRU'RVH6HOHFWLRQRI%06

5DWLRQDOHIRU7HVWLQJ/RZHU'RVHRI%06

5DWLRQDOHIRU'RVH6HOHFWLRQRI)2/),5,

5DWLRQDOHIRU'RVH6HOHFWLRQRI*HPFLWDELQH1DE3DFOLWD[HO

5DWLRQDOHIRU'RVH6HOHFWLRQRI1LYROXPDE

5DWLRQDOHIRU1LYROXPDEPLQXWH,QIXVLRQ

7UHDWPHQW'XUDWLRQ

678'<3238/$7,21

,QFOXVLRQ&ULWHULD

([FOXVLRQ&ULWHULD

/LIHVW\OH5HVWULFWLRQV

0HDOVDQG'LHWDU\5HVWULFWLRQV

&DIIHLQH$OFRKRODQG7REDFFR

$FWLYLW\

6FUHHQ)DLOXUHV

5HWHVWLQJ'XULQJ6FUHHQLQJRU/HDG,Q3HULRG

75($70(17

7UHDWPHQWV$GPLQLVWHUHG

0HWKRGRI7UHDWPHQW$VVLJQPHQW

%OLQGLQJ

'RVDJH0RGLILFDWLRQ

'RVH/LPLWLQJ7R[LFLW\

6WRSSLQJ5XOHV'XULQJ3DUW

0DQDJHPHQW$OJRULWKPVIRU,PPXQRRQFRORJ\$JHQWV

*HQHUDO*XLGHOLQHVIRU'RVH0RGLILFDWLRQV

%06'RVH0RGLILFDWLRQV

)2/),5,'RVH0RGLILFDWLRQV

*HPFLWDELQH1DE3DFOLWD[HO'RVH0RGLILFDWLRQV

1LYROXPDE'RVH0RGLILFDWLRQV

'RVH'HOD\VLQ1LYROXPDE&RKRUWERI$UP%DQG$OO&RKRUWVRI
$UP&

&ULWHULDWR5HVXPH7UHDWPHQWLQ1LYROXPDE$UP&DQG&RKRUWE


*XLGHOLQHVIRU3HUPDQHQW'LVFRQWLQXDWLRQLQ1LYROXPDE$UP&
DQG&RKRUWE

7UHDWPHQWRI7UHDWPHQWUHODWHG,QIXVLRQ5HDFWLRQV

7UHDWPHQW%H\RQG3URJUHVVLRQ$UP&RQO\












































Clinical Protocol
BMS-813160
CV202103
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
8
7.0
Approved
930114148
7.0
v
Approved
1.0
v

3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\

7UHDWPHQW&RPSOLDQFH

&RQFRPLWDQW7KHUDS\

3URKLELWHGDQGRU5HVWULFWHG7UHDWPHQWV

3URKLELWHG7UHDWPHQWV

5HVWULFWHG7UHDWPHQWV

2WKHU5HVWULFWLRQVDQG3UHFDXWLRQV

,PDJLQJ5HVWULFWLRQDQG3UHFDXWLRQV

3HUPLWWHG7KHUDS\

3DOOLDWLYH/RFDO7KHUDS\

7UHDWPHQW$IWHUWKH(QGRIWKH6WXG\

',6&217,18$7,21&5,7(5,$

'LVFRQWLQXDWLRQIURP6WXG\7UHDWPHQW

3RVW6WXG\7UHDWPHQW6WXG\)ROORZXS

'LVFRQWLQXDWLRQIURPWKH6WXG\

/RVWWR)ROORZ8S

6WXG\7HUPLQDWLRQ

678'<$66(660(176$1'352&('85(6

(IILFDF\$VVHVVPHQWV

,PDJLQJ$VVHVVPHQWIRUWKH6WXG\

$GYHUVH(YHQWV

7LPH3HULRGDQG)UHTXHQF\IRU&ROOHFWLQJ$(DQG6$(,QIRUPDWLRQ

0HWKRGRI'HWHFWLQJ$(VDQG6$(V

)ROORZXSRI$(VDQG6$(V

5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6$(V

3UHJQDQF\

/DERUDWRU\7HVW5HVXOW$EQRUPDOLWLHV

3RWHQWLDO'UXJ,QGXFHG/LYHU,QMXU\',/,

2WKHU6DIHW\&RQVLGHUDWLRQV

2YHUGRVH

6DIHW\

3K\VLFDO([DPLQDWLRQV

9LWDO6LJQV

(OHFWURFDUGLRJUDPV

&OLQLFDO6DIHW\/DERUDWRU\$VVHVVPHQWV

,PDJLQJ6DIHW\$VVHVVPHQW

3KDUPDFRNLQHWLFV

3KDUPDFRNLQHWLF$VVHVVPHQWRI%06IROORZLQJ%06
0RQRWKHUDS\

3KDUPDFRNLQHWLF$VVHVVPHQWRI%06GXULQJ&KHPRWKHUDS\
&RPELQDWLRQ7UHDWPHQWLQ3DUW$UPV$DQG%

3KDUPDFRNLQHWLF$VVHVVPHQWRI%06DQG3KDUPDFRNLQHWLFDQG
,PPXQRJHQLFLW\$VVHVVPHQWRI1LYROXPDELQ3DUW$UP&DQG3DUW
$UP&DQG$UP'









































Clinical Protocol
BMS-813160
CV202103
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
9
7.0
Approved
930114148
7.0
v
Approved
1.0
v

3KDUPDFRNLQHWLF$VVHVVPHQWRI,ULQRWHFDQ1DE3DFOLWD[HODQG%06
DQG3KDUPDFRNLQHWLFDQG,PPXQRJHQLFLW\$VVHVVPHQWRI
1LYROXPDELQ3DUW$UP$DQG$UP%

3KDUPDFRNLQHWLF6DPSOH$QDO\VHV

3KDUPDFRG\QDPLFV

3KDUPDFRJHQRPLFV

:KROH%ORRG'1$6DPSOLQJ

%LRPDUNHUV

$GGLWLRQDO5HVHDUFK&ROOHFWLRQ

,PPXQRJHQLFLW\$VVHVVPHQWV

+HDOWK(FRQRPLFV250HGLFDO5HVRXUFH8WLOL]DWLRQDQG+HDOWK(FRQRPLFV

67$7,67,&$/&216,'(5$7,216

6DPSOH6L]H'HWHUPLQDWLRQ

3RSXODWLRQVIRU$QDO\VHV

6WDWLVWLFDO$QDO\VHV

(IILFDF\$QDO\VHV

6DIHW\$QDO\VHV

3KDUPDFRNLQHWLF$QDO\VHV

%06LQ0RQRWKHUDS\3KDVH

%06LQ&RPELQDWLRQ3KDVH

1LYROXPDELQ&RPELQDWLRQ3KDVH

,ULQRWHFDQDQG1DE3DFOLWD[HOLQ&RPELQDWLRQ3KDVH3DUW

,PPXQRJHQLFLW\$QDO\VHV

%LRPDUNHU$QDO\VHV

(&*$QDO\VHV

2WKHU$QDO\VHV

,QWHULP$QDO\VHV

5()(5(1&(6

$33(1',&(6

$33(1',;$%%5(9,$7,216$1'75$'(0$5.6

$33(1',;678'<*29(51$1&(&216,'(5$7,216

$33(1',;$'9(56((9(176$1'6(5,286$'9(56((9(176
'(),1,7,216$1'352&('85(6)255(&25',1*(9$/8$7,1*
)2//2:83$1'5(3257,1*

$33(1',;:20(12)&+,/'%($5,1*327(17,$/'(),1,7,216$1'
0(7+2'62)&2175$&(37,21

$33(1',;5(63216((9$/8$7,21&5,7(5,$,162/,'780256
*8,'(/,1(69(56,21:,7+%0602',),&$7,216

$33(1',;0$1$*(0(17$/*25,7+06

$33(1',;(&2*3(5)250$1&(67$7866&$/(

$33(1',;&<3$$1'3*3*8,'$1&(

$33(1',;0$7(,1+,%,7256*8,'$1&(

$33(1',;8*7$*8,'$1&(

$33(1',;0$7(68%675$7(6*8,'$1&(

$33(1',;&25($1'(;7(1'('$'0(*(1(/,67

$33(1',;5(9,6('35272&2/6800$5<2)&+$1*(+,6725<










































Clinical Protocol
BMS-813160
CV202103
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
10
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
1
SYNOPSIS
Protocol Title: A Phase 1b/2 Study of BMS-813160 in Combination with Chemotherapy or 
Nivolumab in Patients with Advanced Solid Tumors
Short Title: 
A Study of BMS-813160 in Combination with Chemotherapy or Nivolumab in Patients with 
Advanced Solid Tumors
Study Phase:
Phase 1b/2
Rationale:
This is a Phase 1b/2, first-in-oncology study of BMS-813160, a dual antagonist of 
cysteine-cysteine (C-C) chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) in 
participants with advanced colorectal and pancreatic cancers.
Treatment options for patients with metastatic colon or rectal cancer are predominantly 
5-fluorouracil (5-FU) and leucovorin containing regimens in combination with either oxaliplatin 
or irinotecan (FOLFOX or FOLFIRI) with a biologic agent such as bevacizumab. Switching from 
FOLFOX to FOLFIRI in second-line (2L) and vice versa showed no difference in survival in 
metastatic colorectal cancer (CRC) with median overall survival (OS) of 21.5 months vs 20.6 
months. FOLFIRI is being used in this trial as 2L chemotherapy in CRC to avoid any potential 
drug-drug interaction (DDI) between BMS-813160 and oxaliplatin. Bevacizumab or its biosimilar 
can be added to 2L FOLFIRI if it is appropriate and available locally as part of standard of care.
Treatment options for patients with metastatic pancreatic cancer are limited. Gemcitabine (Gem) 
combined with nab-paclitaxel (ABRAXANE®) is a United States (US) Food and Drug 
Administration (FDA) approved first-line (1L) treatment for patients with advanced pancreatic 
cancers. This regimen showed a median progression-free survival (PFS) of 5.5 months and a 
median OS of 8.5 months and is the predominantly used regimen in metastatic pancreatic cancer.
Patients with advanced pancreatic cancer can be treated with 5-FU/liposomal irinotecan in the 2L 
setting and patients with advanced CRC are treated with regorafenib or trifluridine/tipiracil in the 
third-line (3L) setting. However, outcomes with these agents are generally poor with low objective 
response rate (ORR), a median PFS of only 2 to 3 months, and median OS of 6 to 7 months. These 
regimens also have significant toxicity and additional options are clearly needed in advanced 
pancreatic and colorectal cancers. Development of newer and novel agents in the treatment of these 
diseases resistant to chemotherapy is an area of unmet need.
CCR2 and CCR5 are two chemokine receptors that are expressed on myeloid cell and T-cell 
infiltrates in the tumor microenvironment (TME). Each receptor has been separately shown to be 
an important player in multiple models of cancer, including pancreatic cancer and CRC. Therefore, 
targeting both receptors with a small-molecule dual antagonist is a potential novel treatment for 
Revised Protocol No.: 06
Date: 05-Dec-2019
11
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
cancer where compelling evidence supports that myeloid and regulatory T cells (Treg) play a key 
role in mediating immune suppression within the TME.
Clinical data support targeting CCR2 to reverse the immunosuppressive TME in pancreatic cancer. 
Similarly, CCR5 has been targeted in the treatment of CRC. Given the clinical data with CCR2 
and CCR5 antagonism individually in CRC and pancreatic cancer, the potential exists that dual 
CCR2/5 targeting in combination with chemotherapy may lead to even greater benefit. Inhibition 
of the tumor promoting effects of CCR2 and CCR5 signaling in the TME may work synergistically 
with chemotherapy and the lack of overlapping toxicity with chemotherapy also supports 
combining chemotherapy with a CCR2/5 inhibitor.
The immune effects seen with targeting the CCR2/5 pathways suggest that combination with other 
immune agents such as nivolumab, a monoclonal antibody that blocks the programmed death-1 
pathway, may provide additional benefit. Thus, this initial cancer trial of BMS-813160 will also 
study a combination with nivolumab in participants with advanced CRC or pancreatic cancer.
Study Population:
Participants must be at least 18 years old with a histological or cytological confirmed diagnosis of 
an advanced CRC or pancreatic cancer and measurable disease per Response Evaluation Criteria 
in Solid Tumors (RECIST) v1.1.
Objectives and Endpoints:
This 
study 
will 
evaluate 
the 
safety 
profile, 
tolerability, 
pharmacokinetics 
(PK), 
pharmacodynamics, and preliminary efficacy of BMS-813160 alone or in combination with either 
chemotherapy or nivolumab or chemotherapy plus nivolumab in participants with metastatic 
colorectal and pancreatic cancers. The study will be conducted in 2 parts. Part 1 will evaluate 
safety, tolerability, PK, and pharmacodynamics of 2 different doses of BMS-813160 (ie, 300 mg 
twice a day [BID] or 600 mg once daily [QD]) in combination with either FOLFIRI (Arm A),
Gem/ nab-paclitaxel (ABRAXANE ) [Arm B], or nivolumab (Arm C) in participants with 
advanced colorectal and pancreatic cancers. Part 1 Arm C evaluated the PK and 
pharmacodynamics of low dose BMS-813160 (300 mg daily and 150 mg daily) in combination 
with nivolumab in patients with advanced colorectal cancer. Part 2 is a dose expansion study to 
assess preliminary efficacy of BMS-813160 alone (Arm D) or in combination with either 
chemotherapy or nivolumab or chemotherapy plus nivolumab in participants with advanced CRC
or pancreatic cancer. Arm D (BMS-813160 monotherapy) will only open if participants in Arm C 
show an ORR of approximately 15% or durable responses are seen with the combination of 
nivolumab and BMS-813160, and will be important to evaluate the contribution of components.
The objectives and endpoints for the primary, secondary, and exploratory analyses of this study 
are shown in Table 1-1 (Part 1) and Table 1-2 (Part 2).
Revised Protocol No.: 06
Date: 05-Dec-2019
12
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 1-1:
Objectives and Endpoints (Part 1)
Objectives
Endpoints
Primary
1) To assess the safety and tolerability of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel (Arm B), or nivolumab (Arm C) in 
participants with advanced CRC or pancreatic cancer
2) To assess the pharmacodynamic effects of BMS-813160 in 
tumor samples
1a) Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs leading to 
discontinuation, and death; Incidence of 
laboratory abnormalities
1b) Additional safety endpoints: summary 
measurements of vital signs or ECGs
2)
Decrease in Treg or TAM in tumor samples
Secondary
1) To assess the preliminary efficacy of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel (Arm B), or nivolumab (Arm C) in 
participants with advanced CRC or pancreatic cancer
2) To characterize the PK of BMS-813160 and its metabolite 
(BMS-939429) when administered alone, and in 
combination with either Gem + nab-paclitaxel, FOLFIRI or 
nivolumab
3) To characterize the immunogenicity of nivolumab when 
administered in combination with BMS-813160
1)
ORR, median DOR, and PFS rate at 
24 weeks
2a) PK parameters, such as Cmax, Tmax, 
Ctrough, C24, AUC(0-8), AUC(0-24), 
CLT/F, AI, CLR, %UR, MR_Cmax, and 
MR_AUC(0-24), if data permit
2b) Cmax and Ctrough concentrations of 
BMS-813160 during combination therapy
3)
Frequency of positive ADA to nivolumab 
during combination therapy
Exploratory
1) To characterize the PK of nivolumab when administered in 
combination with BMS-813160
2) To assess the potential effect of BMS-813160 monotherapy 
on the CLR of NMN an endogenous biomarker for 
multidrug and toxin extrusion transporters (MATE1 and 
MATE2-K)
3) To assess the potential effect of BMS-813160 monotherapy 
on levels of NMN, an endogenous marker for renal 
transporters
4) To assess the pharmacodynamic effects of BMS-813160 in 
peripheral blood
5) To assess OS
1)
Concentrations at end of infusion and 
Ctrough for nivolumab during combination 
therapy
2,3)Change of NMN in plasma and urine and CL 
change of creatinine levels in plasma and 
urine and CLR
4)
Change of MCP-1 and CCR2 positive
monocyte count in peripheral blood
5)
OS rate at 1 year and 2 years
Abbreviations: %UR = percent urinary recovery over dosing interval; ADA = anti-drug antibody; AEs = adverse
events; AI = accumulation index; AUC(0-8) = area under the concentration-time curve from time 0 to 8 hours post 
dose; AUC(0-24) = area under the concentration-time curve from time 0 to 24 hours post dose; C24 = observed 
plasma concentration at 24 hours post dose (for QD dosing only); CCR2 = cysteine-cysteine chemokine receptor 
2; CL = clearance; CLR = renal clearance; CLT/F = apparent total body clearance; Cmax = maximum observed 
plasma concentration; CRC = colorectal cancer; Ctrough = trough observed plasma concentration; DLT = dose 
limiting toxicity; DOR = duration of response; ECGs = electrocardiograms; FOLFIRI = FOL (folinic acid 
[leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; MATE = 
multidrug and toxin extrusion protein; MCP-1 = monocyte chemotactic protein-1; MR_AUC(0-24) = ratio of 
metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight; MR_Cmax = ratio of metabolite 
Cmax to parent Cmax, corrected for molecular weight; NMN = N-methylnicotinamide; ORR = objective response 
rate; OS = overall survival; PFS = progression-free survival; PK = pharmacokinetic(s); SAEs = serious adverse 
events; TAM = tumor-associated macrophages; Tmax = time of maximum observed plasma concentration; 
Treg = regulatory T cells.
Revised Protocol No.: 06
Date: 05-Dec-2019
13
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 1-2:
Objectives and Endpoints (Part 2)
Objectives
Endpoints
Primary
1) To assess the preliminary efficacy of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel or nivolumab + Gem + nab-paclitaxel 
(Arm B), or nivolumab (Arm C), and as monotherapy 
(Arm D) in participants with advanced CRC or pancreatic 
cancer
1)
ORR as assessed by investigator using 
RECIST v1.1, median DOR, and PFS Rate at 
24 weeks
Secondary
1) To assess the safety and tolerability of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel or nivolumab + Gem + nab-paclitaxel
(Arm B), or nivolumab (Arm C), and as monotherapy 
(Arm D) in participants with advanced CRC or pancreatic 
cancer
2) To assess the pharmacodynamic effects of BMS-813160 in 
tumor samples
1a) Incidence of AEs, SAEs, AEs leading to 
discontinuation, and death; incidence of 
laboratory abnormalities.
1b) Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria in Cohort 3b
1c) Additional safety endpoints: summary 
measures of vital signs or ECG
2)
Decrease in Treg & TAM in tumor samples
Exploratory
1) To assess the PK of BMS-813160 when administered as 
monotherapy and with different chemotherapy or nivolumab 
combination regimens
2) To characterize the immunogenicity of nivolumab when 
administered in combination with BMS-813160 or 
BMS-813160 plus chemotherapies
3) To assess the pharmacodynamic effects of BMS-813160 in 
peripheral blood
4) To assess the PK of irinotecan and nab-paclitaxel in a subset 
of participants when combined with BMS-813160
5) To assess OS
1a) Cmax and Ctrough concentrations of 
BMS-813160 during monotherapy and 
combination therapy
1b) Concentrations at end of infusion and 
Ctrough for nivolumab during combination 
therapy
2)
Frequency of positive ADA to nivolumab 
during combination therapy
3)
Change of MCP-1 and CCR2 positive 
monocyte count in peripheral blood
4)
Cmax, Tmax, AUC(0-24), Ctrough of 
irinotecan, SN-38, and nab-paclitaxel
5)
OS rate at 1 year and 2 years
Abbreviations: ADA = anti-drug antibody; AEs = adverse events; AUC(0-24) = area under the concentration-time 
curve from time 0 to 24 hours post dose; CCR2 = cysteine-cysteine chemokine receptor 2; Cmax = maximum 
observed plasma concentration; CRC = colorectal cancer; Ctrough = trough observed plasma concentration; 
DLT = dose-limiting toxicity; ECGs = electrocardiograms; FOLFIRI = FOL (folinic acid [leucovorin]) F 
(fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; MCP-1 = monocyte 
chemotactic protein-1; ORR = objective response rate; OS = overall survival; PK = pharmacokinetics; RECIST = 
Response Evaluation Criteria in Solid Tumors; SAEs = serious adverse events; TAM = tumor-associated 
macrophages; Tmax = time of maximum observed plasma concentration; Treg = regulatory T cells
Overall Design:
This is a Phase 1b/2, open-label, 2-part, multicenter trial to assess the safety, tolerability, 
pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BMS-813160 alone or in 
combination with either FOLFIRI, gemcitabine (Gem)/nab-paclitaxel
(ABRAXANE), 
nivolumab/Gem/nab-paclitaxel, or nivolumab in participants with advanced CRC or pancreatic 
cancer.
The study design scheme is presented in Figure 1-1 (Part 1) and Figure 1-2 (Part 2).
Revised Protocol No.: 06
Date: 05-Dec-2019
14
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Figure 1-1:
Study Design Schematic (Part 1)
Note: FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours [leucovorin may be given concurrently with irinotecan]; 5-FU 
400 mg/m2 bolus followed by 2400 mg/m2 over 46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle.
Note: The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an intravenous infusion over 30 to 40 minutes on Days 1, 8, and 15 
of each 28-day cycle. Administer gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Note: Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks.
Abbreviations: 1L = first-line; 2L = second-line; 3L =third-line; 5-FU = 5-fluorouracil; BID = twice a day; CRC = colorectal cancer; FOLFIRI = FOL (folinic acid 
[leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); m2 = square meter; mg = milligram; MSS = microsatellite stable; QD = once 
daily.
a Bevacizumab, cetuximab, or panitumumab can be added to 1L FOLFIRI if appropriate.
b Participants will continue on the combination until disease progression , intolerance to treatment, meeting discontinuation criteria, or withdrawal of consent.
c Safety follow-up: 30 days for Arms A and B and 100 days for Arm C. Survival follow up to begin after completion of safety follow-up every 12 weeks (± 2 weeks) 
until 2 years after last dose of study treatment.
Revised Protocol No.: 06
Date: 05-Dec-2019
15
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Figure 1-2:
Study Design Schematic (Part 2) - Combination Therapy Expansion
Note 1: FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours [leucovorin may be given concurrently with irinotecan]; 5-FU 
400 mg/m2 bolus followed by 2400 mg/m2 over 46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle.
Note 2: The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an intravenous infusion over 30 to 40 minutes on Days 1, 8, and 
15 of each 28-day cycle. Administer gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Note 3: Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks. In Cohort 3b, administer nivolumab followed by chemotherapy 
30 minutes later.
Revised Protocol No.: 06
Date: 05-Dec-2019
16
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Abbreviations: 1L = first-line; 2L = second-line; 3L =third-line; 5-FU = 5-fluorouracil; BID = twice a day; FOLFIRI  = FOL (folinic acid [leucovorin]) F
(fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; m2 = square meter; mg = milligram; MSS = microsatellite stable; Nivo = 
nivolumab; ORR = objective response rate; PD = progressive disease; QD = once daily.
a Participants will continue on the combination until disease progression , intolerance to treatment, meeting discontinuation criteria, or withdrawal of consent.
b Lower dose: BMS-813160 150 mg QD.
c Participants in Cohort 1c will be allowed to cross over to Cohort 5 at the time of PD if it’s felt to be in their best interest by their treating physician and participants 
meet all eligibility criteria to enroll in Arm C. Participants will have to meet all eligibility criteria to re-enter the study, undergo baseline assessment (Table 2-2) 
and need a 28-day washout period prior to first dose of study treatment in the new arm.
d Safety follow-up: 30 days for Arms A, B (Cohorts 3a and 3c), and D; 100 days for Arm C and Cohort 3b. Survival follow up to begin after completion of safety 
follow-up every 12 weeks (± 2 weeks) until 2 years after last dose of study treatment.
e The Gem/nab-paclitaxel in combination with nivolumab and BMS-813160 cohort had a safety lead-in of approximately 6 participants who were treated with 
BMS-813160 300 mg BID and monitored for 4 weeks before additional participants are added to the cohort. In addition a staggered dosing (sentinel participant) 
approach was used for the first three participants. The first participant to be dosed was observed for 5 days, before additional participants (ie, participant 2 and 
3) received study treatments.
f Arm D (BMS-813160 monotherapy) will only open if participants in Arm C show an ORR of approximately 15% or durable responses are seen with the 
combination of nivolumab and BMS-813160.
g Cohort 4 was closed per Revised Protocol 06. Participants in Cohort 3c can no longer crossover to Cohort 4 per Revised Protocol 06.
h Cohort 7 will not open for enrollment due to Cohort 4 being closed due to futility per Revised Protocol 06.
Revised Protocol No.: 06
Date: 05-Dec-2019
17
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
The study is divided into 3 periods: Screening, Treatment (Part 1 and Part 2), and Follow-up 
(Safety and Survival Phases).
Screening Period:
•
The Screening Period will last for up to 28 days.
•
The Screening Period begins by establishing the participant’s initial eligibility upon signing of 
the informed consent form.
•
Participants will be enrolled using the Interactive Response Technologies or Interactive Web 
Response Systems.
Treatment Period (Part 1):
•
The Treatment Period (Part 1) will have a 2-week monotherapy lead-in with BMS-813160 
prior to combination with either FOLFIRI (Arm A) in 1L CRC, Gem/nab-paclitaxel (Arm B)
in 1L pancreatic, or nivolumab (Arm C) in 2L pancreatic or 2/3L CRC. Participants will 
continue on the combination until disease progression, intolerance to treatment, meeting 
discontinuation criteria, or withdrawal of consent.
•
All 3 arms will enroll participants in parallel. Participants will be assigned to the BMS-813160 
300 mg BID or 600 mg QD cohort in each arm of the study. In Arm C, participants with 2/3L 
CRC can also be assigned to receive 150 mg QD or 300 mg QD. The BMS-813160 
monotherapy lead-in serves the purpose of establishing the safety and tolerability of 
BMS-813160 in oncology patients and facilitating the characterization of the added or 
synergistic toxicity of the subsequent combination regimens. The monotherapy lead-in also 
enables a biopsy at 2 weeks to characterize pharmacodynamic effects of BMS-813160.
•
Approximately 6 evaluable participants will be treated at each BMS-813160 dose (ie, 300 mg 
BID or 600 mg QD) for a total of 12 participants per arm (6 participants per dose per treatment 
arm or per lower doses [150 mg QD and 300 mg QD] of BMS-813160 in combination with 
nivolumab). Up to 6 additional participants may be added to a dose cohort to better characterize 
the safety, PK, or pharmacodynamic profile and inform Part 2 dose selection of BMS-813160 
if needed after discussion with the Sponsor and investigators.
•
After 2 weeks of BMS-813160 monotherapy, participants will have a mandatory biopsy and 
will then start the combination phase with FOLFIRI, Gem/nab-paclitaxel, or nivolumab along 
with continued treatment with BMS-813160. Participants will continue on the combination 
until disease progression, intolerance to treatment, meeting discontinuation criteria, or 
withdrawal of consent.
•
Tumor progression or response endpoints will be assessed using RECIST v1.1 for solid tumors.
Participants with a response of stable disease (SD), partial response (PR), or complete response 
(CR) will continue to the next treatment cycle.
Revised Protocol No.: 06
Date: 05-Dec-2019
18
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Treatment Period (Part 2):
•
The doses of BMS-813160 in Part 2 were chosen based on safety, PK, and pharmacodynamic
data available from Part 1 of the study. Based on these considerations, the BMS-813160 
300 mg BID dosing regimen was selected for primary investigation in this study. A regimen 
of BMS-813160 150 mg QD in combination with FOLFIRI also will be evaluated in Arm A.
•
The Treatment Period (Part 2) will explore the preliminary signals of efficacy of BMS-813160 
in combination with FOLFIRI (Arm A)
in 2L CRC, Gem/nab-paclitaxel or 
nivolumab/Gem/nab-paclitaxel (Arm B) in 1L pancreatic cancer, or nivolumab (Arm C) in 2L 
pancreatic (closed per Revised Protocol 06) and 2/3L CRC microsatellite stable (MSS), and 
as monotherapy (Arm D) in 2L pancreatic and 2/3L CRC: 10 disease-specific cohorts in total,
31 to 35 evaluable participants in each cohort (Arms A, B, and C) and 18 per cohort (Arm D).
•
An additional arm (Arm D) with BMS-813160 monotherapy will only open if participants in 
Arm C show an ORR of approximately 15% or durable responses are seen with the 
combination of nivolumab and BMS-813160.
•
Participants in Cohort 1c will be allowed to cross over to Cohort 5 at the time of disease 
progression if felt to be in their best interest by their treating physician and participants meet 
all eligibility criteria to enroll in Arm C. Participants will have to meet all eligibility criteria to 
re-enter the study and need a 28-day washout period prior to treatment in the new arm.
Participants in Cohort 3c will not be allowed to cross over to Cohort 4 at the time of disease 
progression since Cohort 4 was closed per Revised Protocol 06
•
Tumor progression or response endpoints will be assessed using RECIST v1.1 for solid tumors.
Participants with a response of SD, PR, or CR will continue to the next treatment cycle.
Follow-up Period:
•
Safety Follow-up Phase (Parts 1 and 2):
−
Participants on Arms A, B (Cohorts 3a and 3c), and D must be followed for at least 30 days 
after the last dose of study treatment to monitor for adverse events (AEs).
−
Participants on Arm C and Cohort 3b (Arm B, Part 2) will be followed for at least 100 days 
after the last dose of study treatment to monitor for AEs to account for the long half-life of 
nivolumab.
−
All participants, except those participants who withdraw consent for study participation,
will be required to complete Clinical/Safety Follow-up visits as above (per Table 2-7 in 
Schedule of Activities) after the last dose of study treatment, regardless of whether they 
start a new anti-cancer therapy.
•
Survival Follow-up Phase:
−
After completion of the Safety Follow-up Phase, all participants will enter the Survival 
Follow-up Phase. Participants will be followed up (by telephone or clinic visit) every 
12 weeks (Q12W) [± 2 weeks], from the last dose of study treatment for 2 years or until 
death, loss to follow-up, withdrawal of consent, or conclusion of the study, whichever 
comes first.
Revised Protocol No.: 06
Date: 05-Dec-2019
19
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
−
The duration of this phase is up to 2 years following the last dose of study treatment, 
although a longer follow-up phase could be considered in selected cases if an efficacy 
signal is apparent.
−
Data from imaging assessments for participants who have ongoing clinical benefit may 
continue to be collected while participants complete the survival phase of the study.
Treatment Beyond Progression (Arm C only): Participants will be permitted to continue on study 
treatment beyond initial RECIST v1.1-defined progressive disease as long as they meet the criteria. 
The decision to continue study treatment beyond initial investigator-assessed progression should 
be discussed with the BMS Medical Monitor (or designee) and documented in the study records.
Number of Participants:
Approximately 54 evaluable participants (6 to 9 participants per dose per treatment arm) may be 
treated in Part 1 (monotherapy lead-in/combination safety). If additional participants are enrolled 
(as indicated in Section 5.1.2), approximately 48 additional participants could be enrolled in Part 1 
(6 participants per dose per treatment arm or per lower doses [150 mg QD and 300 mg QD] of 
BMS-813160 in combination with nivolumab). Approximately 308 evaluable participants may be 
treated in Part 2, Cohorts 1a to 8 (efficacy expansion) [approximately 35 evaluable participants 
per tumor indication per treatment in Arms A and B and approximately 31 evaluable participants 
per tumor indication per treatment in Arm C]. For each of the pancreatic and CRC MSS cohorts, 
approximately 18 additional evaluable participants will be treated in a treatment Arm D 
(BMS-813160 monotherapy) [opens if ORR of approximately 15% or durable responses are seen 
in Arm C]. The number of participants will be continuously monitored such that the number of 
evaluable participants in Part 2 will not exceed 40 in any cohort. If the study is expanded further 
to add more participants, a protocol amendment will be submitted justifying the sample size.
Revised Protocol No.: 06
Date: 05-Dec-2019
20
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Treatment Arms and Duration:
Study Treatment:
The study treatment is presented in Table 1-3.
Table 1-3:
Study Treatment for CV202103
Medication
Potency
IP/Non-IMPa
BMS-813160 Capsule
150 mg
IP
BMS-813160 Film Coated Tablet
300 mg
IP
BMS-813160 Film Coated Tablet
75 mg
IP
Nivolumab Injectionb
100 mg/vial (10 mg/mL)
IP
Nivolumab Injectionb
40 mg/vial (10 mg/mL)
IP
Gemcitabine Injectionc
1000 mg/vial and various strengths
IP
Nab-paclitaxel (ABRAXANE)c
100 mg/vial and various strengths
IP
5-FUc
Various strengths
IP
Leucovorinc
Various strengths
IP
Irinotecanc
Various strengths
IP
Abbreviations: 5-FU = 5-fluorouracil; IP = investigational product; Non-IMP = non-investigational medicinal 
product.
a Where allowed by local regulations, chemotherapy treatments may be considered Non-IMP.
b Nivolumab (BMS-936558) will be supplied as a 240 mg kit - each kit containing (2) 100 mg vials and (1) 40 mg 
vial.
c These products will be obtained as local commercial product in countries if allowed by local regulations or through 
investigating site’s standard prescribing procedures, otherwise the Sponsor will supply these products.
Revised Protocol No.: 06
Date: 05-Dec-2019
21
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
The selection and timing of dose for each participant is presented in Table 1-4.
Table 1-4:
Selection and Timing of Dose
Study Treatment
Dosage level(s)
Frequency of Administration
Route of
Administration
BMS-813160
(150 mg capsule or
300 mg tablet)
300 mg
BID
PO
BMS-813160
(150 mg capsule or 
300 mg tablet)
600 mg
QD
PO
BMS-813160
(150 mg capsule or
75 mg tablet)
150 mg
QD
PO
BMS-813160
(150 mg capsule or
300 mg tablet)
300 mg
QD
PO
Nivolumab
480 mg IV
Q4W
IV infusion
5-FU
400 mg/m2 Bolus
AND
2400 mg/m2 IV
Day 1, 15: Q4W
Bolus and IV infusion
Leucovorin
400 mg/m2 IV
Day 1, 15: Q4W
IV infusion
Irinotecan
180 mg/m2 IV
Day 1, 15: Q4W
IV infusion
Gemcitabine
1000 mg/m2 IV
Day 1, 8, 15: Q4W
IV infusion
Nab-paclitaxel
(ABRAXANE)
125 mg/m2 IV
Day 1, 8, 15: Q4W
IV infusion
Abbreviations: 5-FU = 5-fluorouracil; BID = twice a day; IV = intravenous; PO = per os (by mouth [orally]); Q4W = 
every 4 weeks; QD = once daily.
FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours [leucovorin 
may be given concurrently with irinotecan]; 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 over 
46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle. Bevacizumab or its biosimilar 
can be added to 2L FOLFIRI if appropriate, and will be administered in accordance with local 
Health Authority approved labeling for these agents. Levoleucovorin can be substituted for 
leucovorin as per site’s standard practice.
The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an 
intravenous infusion over 30 to 40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer 
gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 
15 of each 28-day cycle.
Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks.
Revised Protocol No.: 06
Date: 05-Dec-2019
22
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Treatment Duration: Participants will be treated until disease progression, intolerance to treatment, 
meeting discontinuation criteria, or withdrawal of consent. Participants in Arm C may be treated 
beyond progression as long as they meet the criteria. Participants who discontinue chemotherapy 
in part or whole due to intolerance can continue BMS-813160 or BMS-813160 and nivolumab 
(Cohort 3b) on study after investigator’s discussion with the medical monitor or Sponsor designee.
Participants will continue to get all study evaluations as per the Schedule of Activities.
Data Monitoring Committee: No
BMS has developed a multi-layered process to ensure safety monitoring through close 
collaboration of study site investigators, the BMS study team, and the BMS Global 
Pharmacovigilance and Epidemiology (GPVE) led Safety Management Team (SMT). This 
collaborative process constitutes the safety monitoring plan for the study. To support safety 
oversight, BMS has established ongoing processes for collection, review, analysis, and submission 
of individual AE reports and their aggregate analyses. Because this is an open-label study, GPVE, 
the BMS medical monitor, and the investigators will have access to all data necessary for safety 
evaluation.
BMS GPVE is an internal group that operates independently from the clinical team to monitor 
safety across all BMS protocols, and analyze all data in an unblinded fashion. Within BMS, an 
SMT is established for investigational therapies under clinical development, and a member of 
GPVE chairs this team. In addition, signal detection is performed at least monthly and ad hoc 
throughout the study by the SMT composed, at a minimum, of the GPVE medical safety 
assessment physician (Chairman of the SMT) and GPVE single case review physician, the study 
medical monitor, the study biostatistician, and epidemiologist; all of whom, analyze the data in an 
unblinded fashion. Furthermore, the SMT routinely monitors for actual or potential issues related 
to participant safety that could result in a change in the medical risk-benefit balance associated 
with the use of study treatment(s).
Revised Protocol No.: 06
Date: 05-Dec-2019
23
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
2
SCHEDULE OF ACTIVITIES
Study assessments and procedures are presented in the following tables:
•
Table 2-1: Screening Procedural Outline
•
Table 2-2: Baseline for Cross-Over Procedural Outline - Cohort 1c to Cohort 5
- Cohort 3c to Cohort 4 (Closed per Revised Protocol 06) - Part 2
•
Table 2-3: On-treatment Procedural Outline - Arm A - Parts 1 and 2
•
Table 2-4: On-treatment Procedural Outline - Arm B - Parts 1 and 2
•
Table 2-5: On-treatment Procedural Outline - Arm C - Parts 1 and 2 (Including Cross Over)
•
Table 2-6: On-treatment Procedural Outline - Arm D - Monotherapy Alone
•
Table 2-7: Follow-up Procedural Outline
In limited circumstances, assessments and procedures may occur outside the indicated timeframes
due to scheduling issues, but the Sponsor should be notified.
Revised Protocol No.: 06
Date: 05-Dec-2019
24
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-1:
Screening Procedural Outline - Parts 1 and 2 (CV202103)
Procedure
Day -28 to Day -1
Notes
Eligibility Assessments
Informed Consent
X
A participant is considered enrolled only when a protocol specific informed consent is 
signed. Obtain patient identification number via IRT after signing of the written informed 
consent.
Utilize IRT
X
To obtain patient identification number. After completing all screening procedures, utilize 
IRT to either screen fail or obtain assignment information, as applicable. 
Assignment/Randomization can occur up to 5 days prior to first dose.
Inclusion/Exclusion Criteria
X
All inclusion/exclusion criteria should be assessed at screening and confirmed prior to 
first dose.
Medical History
X
Includes prior conditions and any toxicities or allergy related to previous treatments and
any known mutation status.
Prior Anti-cancer Therapy
X
Prior anti-cancer therapy including radiotherapy, surgery, and systemic therapy.
ECOG Status Assessment
X
See Appendix 7.
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 24 hours prior to first dose, then a single exam 
may count as both the screening and pre-dose evaluation.
Physical Measurements
X
Includes height, weight, and BMI.
Vital Signs
X
Includes body temperature, respiratory rate, pulse oximetry, and seated blood pressure and 
heart rate. Blood pressure and heart rate should be measured after the participant has been 
resting quietly for at least 5 minutes.
Concomitant Medication Use
X
Includes medications taken within 4 weeks prior to treatment.
Electrocardiogram (ECG)
X
ECGs should be recorded after the participant has been supine for at least 5 minutes.
Clinical Complaints
X
Clinical complaints related to the disease under study present 14 days prior to the first 
dose of study treatment must be collected.
Laboratory Tests
Serology, Hematology, Serum Chemistry, 
Thyroid Panel, and Urinalysis
X
See Section 9.4.4
Pregnancy Test (Serum or Urine)
X
For WOCBP only. Serum or urine within 24 hours prior to first dose of assigned study 
treatment. See Section 6.1.
Revised Protocol No.: 06
Date: 05-Dec-2019
25
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-1:
Screening Procedural Outline - Parts 1 and 2 (CV202103)
Procedure
Day -28 to Day -1
Notes
Follicle Stimulating Hormone (FSH)
X
Only women not considered WOCBP. Refer to Appendix 4 for definitions and guidelines.
Disease Assessment
X
MSS status for CRC patients in Arm C and D. Please see inclusion criteria (Section 6.1) 
for details. Document MSI status for Arm A and B participants if results are available.
Baseline Tumor Assessment
X
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known 
and/or suspected sites of disease within 28 days prior to date of first dose.
Participants with symptoms or history of brain metastasis should have a MRI of the brain 
without and with contrast. CT of the brain without and with contrast can be performed if 
MRI is contraindicated. 
Bone scans should be performed as clinically indicated per local standards.
Mandatory Pre-Treatment Biopsy
X
Biopsy must be performed during the Screening Phase in all participants prior to first dose 
of assigned treatment unless adequate tumor tissue is confirmed from a biopsy done in the
preceding 90 days with no intervening therapy. Please see lab manual for details on 
biopsy collection. Residual sample(s) may be retained for additional research.
Sufficient tumor tissue must be obtained and centrally or locally confirmed before start of 
study treatment (3 to 4 blocks or minimum of 30 slides), obtained by a core needle biopsy, 
incisional biopsy, or excisional biopsy.
Archival Tumor Tissue Block
X
See Section 6.1. Residual samples may be retained for additional research.
Biomarker Sample Collection
X
See Section 9.8 (Table 9.8-1 and Table 9.8-2). Residual samples may be retained for 
additional research. Genotyping sample will be collected.
Adverse Event Reporting
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of participant’s written consent until 30 days 
(100 days for Arm C and Cohort 3b [Arm B, Part 2]) after discontinuation of dosing or 
participant’s participation in the study. All SAEs and AEs will be assessed using NCI 
CTCAE v4.03.
Abbreviations: AE = adverse event; BMI = body mass index; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECG = 
electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FSH = follicle stimulating hormone; IRT = Interactive Response Technologies; MRI = magnetic 
resonance imaging; MSI = microsatellite instability; MSS = microsatellite stable; NCI = National Cancer Institute; PE = physical examination; RECIST = Response 
Evaluation Criteria in Solid Tumors; SAE = serious adverse event; WOCBP = women of child bearing potential.
Revised Protocol No.: 06
Date: 05-Dec-2019
26
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-2:
Baseline for Cross-Over Procedural Outline - Cohort 1c to Cohort 5 - Cohort 3c to Cohort 4 (Closed 
per Revised Protocol 06) - Part 2 (CV202103)
Procedure
Day -28 to Day -1
Notes
Eligibility Assessments
Informed Consent
X
Participants must sign informed consent for cross-over treatment in Arm C. 
Inclusion/Exclusion Criteria
X
All inclusion/exclusion criteria for Arm C should be assessed at the cross-over baseline 
visit and confirmed prior to first dose.
ECOG Status Assessment
X
See Appendix 7.
Safety Assessments
Physical Examination (PE)
X
If the cross-over baseline PE is performed within 24 hours prior to dosing on Day 1, then 
a single examination may count as both the cross-over baseline and pre-dose evaluation.
Physical Measurements
X
Includes weight.
Vital Signs
X
Includes body temperature, respiratory rate, pulse oximetry, and seated blood pressure and 
heart rate. Blood pressure and heart rate should be measured after the participant has been 
resting quietly for at least 5 minutes.
Electrocardiogram (ECG)
X
ECGs should be recorded after the participant has been supine for at least 5 minutes.
Laboratory Tests
Serology, Hematology, Serum Chemistry, 
Thyroid Panel, and Urinalysis
X
See Section 9.4.4
Pregnancy Test (Serum or Urine)
X
For WOCBP only. Serum or urine within 24 hours prior to first dose of assigned study 
treatment. See Section 6.1.
Disease Assessment
X
MSS status for CRC patients in Arm C.
Baseline Tumor Assessment
X
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known 
and/or suspected sites of disease within 28 days prior to date of first dose. Re-baseline of 
target lesions and non-target lesions should be performed as per RECIST v1.1.
Mandatory Pre-Treatment Biopsy
X
A mandatory pretreatment fresh tumor biopsy must be performed.
Sufficient tumor tissue must be obtained and centrally or locally confirmed before start of 
study treatment (3 to 4 blocks or minimum of 30 slides), obtained by a core needle biopsy, 
incisional biopsy, or excisional biopsy.
Revised Protocol No.: 06
Date: 05-Dec-2019
27
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-2:
Baseline for Cross-Over Procedural Outline - Cohort 1c to Cohort 5 - Cohort 3c to Cohort 4 (Closed 
per Revised Protocol 06) - Part 2 (CV202103)
Procedure
Day -28 to Day -1
Notes
Biomarker Sample Collection
X
See Section 9.8 (Table 9.8-2). Residual samples may be retained for additional research. 
Genotyping/SNP sample will be not be collected. All other biomarker samples will be 
collected as per Table 9.8-2.
Adverse Event Reporting
Monitor for Adverse Events
X
All AEs must continue to be collected for 100 days after discontinuation of the cross over.
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of participant’s written consent until 100 days 
after discontinuation of dosing or participant’s participation in the study. All SAEs and 
AEs will be assessed using NCI CTCAE v4.03.
Note: Cohort 4 was closed per Revised Protocol 6. Participants in Cohort 3c that progress on treatment cannot cross over to Cohort 4 per Revised Protocol 06.
Abbreviations: AE = adverse event; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG 
= Eastern Cooperative Oncology Group; FSH = follicle stimulating hormone; MRI = magnetic resonance imaging; MSS = microsatellite stable; NCI = National 
Cancer Institute; PE = physical examination; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; SNP = single nucleotide 
polymorphism; WOCBP = women of child bearing potential.
Revised Protocol No.: 06
Date: 05-Dec-2019
28
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-3:
On-treatment Procedural Outline - BMS-813160/FOLFIRI (Arm A) - Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15
D28
EOT
Notes
Eligibility Assessments
Inclusion/Exclusion 
Criteria
X
X
For Part 1 (C0D-1) & Part 2 (C1D1): Participants 
must meet all eligibility criteria before starting 
treatment.
Utilize IRT
X
X
X
X
For all participants at Cycle 1 Day 1, each 
subsequent dosing visit and to discontinue 
participant (EOT).
Safety Assessments
Physical Examination
X
X
X
X
X
For Part 1 (C0D1) & Part 2 (C1D1) and Day 1 of 
each cycle: perform a complete physical 
examination within 24 hours of dose 
administration.
On subsequent visits in each cycle, perform a 
symptom-directed physical examination within 
24 hours of dose administration.
Vital Signs
X
X
X
X
X
Including weight, body temperature, respiratory 
rate, pulse oximetry, seated blood pressure and 
heart rate.
Approximately the same time as the ECG.
On days when there is a pre-dose and 2 hour 
post-dose ECG, vital signs except weight should 
be taken at the time of each ECG.
ECOG Assessment
X
X
X
X
X
12-Lead ECG
X
X
X
X
X
ECGs should be recorded after the participant 
has been supine for at least 5 minutes.
Collection prior to and 2 hours post 
BMS-813160 administration for Cycles 0, 1, and 
2. Only pre-dose ECG will be obtained for 
Revised Protocol No.: 06
Date: 05-Dec-2019
29
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-3:
On-treatment Procedural Outline - BMS-813160/FOLFIRI (Arm A) - Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15
D28
EOT
Notes
subsequent cycles. Pre-dose ECGs must be done 
regardless of dosing schedule.
Triplicate ECG at least one minute apart prior to
C0D1 (Part 1) or C1D1 (Part 2) dose only.
Serious Adverse Event 
Assessment
All SAEs must be collected from the date of the participant’s written consent until 
30 days post discontinuation of dosing or participant’s participation in the study if 
the last scheduled visit occurs at a later time.
SAEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Adverse Events 
Assessment
Nonserious adverse events are collected from first dose through 30 days after last 
dose of study treatment
AEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Concomitant
Medication Use
X
X
X
X
X
Laboratory Tests
Hematology, Chemistry
X
X
X
X
X
There will be a -3 day window for collection of 
Hematology & Chemistry laboratory tests.
(See Section 9.4.4)
Thyroid Function Panel
X
X
X
X
Includes TSH, Free T3 and Free T4. There will 
be a -3 day window for collection of Thyroid 
Function Panel. (See Section 9.4.4)
Pregnancy Test
(Serum or Urine)
X
X
X
WOCBP: Serum or urine pregnancy test must be
performed within 24 hours prior to 
administration of study treatment and on Day 1 
of each cycle regardless of dosing schedule.
Pharmacokinetics
See Table 9.5.1-1, Table 9.5.2-1, Table 9.5.4-1, and Table 9.5.4-2
See Section 9.5.1 (Table 9.5.1-1) for MATE-renal 
transporter blood and urine samples to be 
collected.
See Section 6.3.1 for fasting requirements for PK 
sampling.
Biomarkers
See Table 9.5.1-1, Table 9.8-1, and Table 9.8-2
Revised Protocol No.: 06
Date: 05-Dec-2019
30
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-3:
On-treatment Procedural Outline - BMS-813160/FOLFIRI (Arm A) - Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15
D28
EOT
Notes
Mandatory 
On-treatment Biopsy
X
X
Note: Biopsy on C0D14 of Part 1 OR C1D28 of 
Part 2.
Monotherapy should continue if biopsy is 
collected beyond C0D14; combination with 
FOLFIRI should only begin after the biopsy in 
Part 1.
Participants on bevacizumab or its biosimilar 
should be off bevacizumab or its biosimilar for at 
least 14 days or according to institutional 
guidelines to prevent any bleeding or delay in 
wound healing.
Progression Driven 
Biopsy
At disease progression (see note)
Tissue submission is optional and biopsy is not 
required by protocol.
Efficacy Assessments
Tumor Response
Assessment (CT/MRI)
To be performed every 8 weeks (± 1 week) from C1D1 in all arms. This was 
done since Part 1 has monotherapy for 2 weeks.
The same modality that is selected at screening should be used for each 
assessment. Assessed by RECIST v1.1 criteria (see Appendix 5).
Study Treatment
BMS-813160
BMS-813160 is taken daily according to assigned dose.
Site to check participant’s pill diary at each visit
FOLFIRIa
X
X
Infusions given on Day 1 and Day 15 of each 
cycle. (See Section 7.1)
5-FU infusion over 46 hours.
Note: In the event of multiple procedures are required at a single time point, the following is a list of procedures from highest priority to low: pharmacokinetic 
sampling, ECG and vital signs, and laboratory tests.
Abbreviations: 2L = second line; 5-FU = 5-fluorouracil; C0D1 = Cycle 0, Day 1; C0D14 = Cycle 0, Day 14; C1D1 = Cycle 1, Day 1; C1D28 = Cycle 1, Day 28; 
CT = computed tomography; D -1 = Day -1; D1 = Day 1; D14 = Day 14; D15 = Day 15; D2 = Day 2; D28 = Day 28; D3 = Day 3; D7 = Day 7; ECG = 
electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; IRT = Interactive Response Technologies; MATE = multidrug and 
toxin extrusion protein; MRI = magnetic resonance imaging; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; T3 = 
triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; wk(s) = week(s); WOCBP = women of child bearing potential
a Bevacizumab or its biosimilar can be added to 2L FOLFIRI if appropriate.
Revised Protocol No.: 06
Date: 05-Dec-2019
31
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-4:
On-treatment Procedural Outline - BMS-813160/Gemcitabine/Nab-paclitaxel/Nivolumab (Arm B) -
Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D8
D15
D28
EOT
Notes
Eligibility Assessments
Inclusion/Exclusion 
Criteria
X
X
For Part 1 (C0D-1) & Part 2 (C1D1):
Participants must meet all eligibility criteria 
before starting treatment.
Utilize IRT
X
X
X
X
X
For all participants at Cycle 1 Day 1, each 
subsequent dosing visit and to discontinue 
participant (EOT)
Safety Assessments
Physical Examination
X
X
X
X
X
For Part 1 (C0D1) & Part 2 (C1D1) and Day 1 
of each cycle: perform a complete physical 
examination within 24 hours of dose 
administration.
On subsequent visits in each cycle, perform a 
symptom-directed physical examination within 
24 hours of dose administration.
Vital Signs
X
X
X
X
X
X
Including weight, body temperature, respiratory 
rate, pulse oximetry, seated blood pressure and 
heart rate.
Approximately the same time as the ECG.
On days when there is a pre-dose and 2 hour 
post-dose ECG, signs except weight should be 
taken at the time of each ECG.
ECOG Assessment
X
X
X
X
X
Revised Protocol No.: 06
Date: 05-Dec-2019
32
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-4:
On-treatment Procedural Outline - BMS-813160/Gemcitabine/Nab-paclitaxel/Nivolumab (Arm B) -
Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D8
D15
D28
EOT
Notes
12-Lead ECG
X
X
X
X
X
ECGs should be recorded after the participant 
has been supine for at least 5 minutes.
ECG prior to and 2 hours post BMS-813160 
administration for Cycles 0, 1, and 2. Only pre-
dose ECG will be obtained for subsequent 
cycles. Pre-dose ECGs must be done regardless 
of dosing schedule.  
Triplicate ECG at least one minute apart prior to 
C0D1 (Part 1) & C1D1 (Part 2) dose only.
Serious Adverse Event 
Assessment
All SAEs must be collected from the date of the participant’s written consent until 
30 days or 100 days (Cohort 3b [Arm B, Part 2]) post discontinuation of dosing or 
participant’s participation in the study if the last scheduled visit occurs at a later 
time.
SAEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Adverse Events 
Assessment
Nonserious adverse events are collected from first dose through 30 days or 100 days 
(Cohort 3b [Arm B, Part 2]) after last dose of study treatment
AEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Concomitant
Medication Use
X
X
X
X
X
X
Laboratory Tests
Hematology, Chemistry
X
X
X
X
X
X
There will be a -3 day window for collection of 
Hematology & Chemistry laboratory tests.
(See Section 9.4.4)
Thyroid Function Panel
X
X
X
X
Includes TSH, Free T3 and Free T4. There will 
be a -3 day window for collection of Thyroid 
Function Panel. (See Section 9.4.4)
Pregnancy Test
(Serum or Urine)
X
X
X
WOCBP: Serum or urine pregnancy test must be
performed within 24 hours prior to 
administration of study treatment and on Day 1 
of each cycle regardless of dosing schedule.
Revised Protocol No.: 06
Date: 05-Dec-2019
33
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-4:
On-treatment Procedural Outline - BMS-813160/Gemcitabine/Nab-paclitaxel/Nivolumab (Arm B) -
Parts 1 and 2 (CV202103)
Part 1
Cycle 0
(2-wk monotherapy)
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D8
D15
D28
EOT
Notes
Pharmacokinetics
See Table 9.5.1-1, Table 9.5.2-1, Table 9.5.4-1, and Table 9.5.4-2
See Section 9.5.1 (Table 9.5.1-1) for 
MATE-renal transporter blood and urine 
samples to be collected.
See Section 6.3.1 for fasting requirements for PK 
sampling.
Biomarkers
See Table 9.5.1-1, Table 9.8-1, and Table 9.8-2
Mandatory 
On-treatment Biopsy
X
X
Note: Biopsy on C0D14 of Part 1 OR C1D28 of 
Part 2
Monotherapy should continue if biopsy is 
collected beyond C0D14; combination with 
gemcitabine/nab-paclitaxel should only begin 
after the biopsy in Part 1.
Progression Driven 
Biopsy
At disease progression (see note)
Tissue submission is optional and biopsy is not 
required by protocol.
Efficacy Assessments
Tumor Response
Assessment (CT/MRI)
To be performed every 8 weeks (± 1 week) from date of first dose.
The same modality that is selected at screening should be used for each 
assessment. Assessed by RECIST v1.1 criteria (see Appendix 5).
Study Treatment
BMS-813160
BMS-813160 is taken daily according to assigned dose.
Site to check participant’s pill diary at each visit
Gemcitabine
/nab-paclitaxel
X
X
X
Nivolumab
X
Nivolumab infusion given over 30 minutes on 
Day 1 of each cycle for Cohort 3b in Part 2.
Note: In the event of multiple procedures are required at a single time point, the following is a list of procedures from highest priority to low: pharmacokinetic 
sampling, ECG and vital signs, and laboratory tests.
Abbreviations: C0D1 = Cycle 0, Day 1; C0D14 = Cycle 0, Day 14; C1D1 = Cycle 1, Day 1; C1D28 = Cycle 1, Day 28; CT = computed tomography; D -1 = Day -1; 
D1 = Day 1; D14 = Day 14; D15 = Day 15; D2 = Day 2; D28 = Day 28; D3 = Day 3; D7 = Day 7; D8 = Day 8; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; EOT = end of treatment; IRT = Interactive Response Technologies; MATE = multidrug and toxin extrusion protein; MRI = 
Revised Protocol No.: 06
Date: 05-Dec-2019
34
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
magnetic resonance imaging; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; T3 = triiodothyronine; T4 = thyroxine; 
TSH = thyroid stimulating hormone; wk(s) = week(s); WOCBP = women of child bearing potential.
Revised Protocol No.: 06
Date: 05-Dec-2019
35
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-5:
On-treatment Procedural Outline - BMS-813160/Nivolumab (Arm C) - Parts 1 and 2 (Including Cross 
Over) [CV202103]
Part 1
Cycle 0
2-wk monotherapy
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15a
D28
EOT
Notes
Eligibility Assessments
Inclusion/Exclusion 
Criteria
X
X
For Part 1 (C0D-1) & Part 2 (C1D1): 
Participants must meet all eligibility criteria 
before starting treatment.
Utilize IRT
X
X
X
For all participants at Cycle 1 Day 1, each 
subsequent dosing visit and to discontinue 
participant (EOT)
Safety Assessments
Physical Examination
X
X
X
X
X
For Part 1 (C0D1) & Part 2 (C1D1) and Day 1 of 
each cycle: perform a complete physical 
examination within 24 hours of dose 
administration.
On subsequent visits in each cycle, perform a 
symptom-directed physical examination within 
24 hours of dose administration.
Vital Signs
X
X
X
X
X
Including weight, body temperature, respiratory 
rate, pulse oximetry, seated blood pressure and 
heart rate.
Approximately the same time as the ECG.
On days when there is a pre-dose and 2 hour 
post-dose ECG, vital signs except weight should 
be taken at the time of each ECG.
ECOG Assessment
X
X
X
X
X
12-Lead ECG
X
X
X
X
X
ECGs should be recorded after the participant 
has been supine for at least 5 minutes.
ECG prior to and 2 hours post BMS-813160 
administration for Cycles 0, 1, and 2. Only pre-
dose ECG will be obtained for subsequent 
cycles.
Revised Protocol No.: 06
Date: 05-Dec-2019
36
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-5:
On-treatment Procedural Outline - BMS-813160/Nivolumab (Arm C) - Parts 1 and 2 (Including Cross 
Over) [CV202103]
Part 1
Cycle 0
2-wk monotherapy
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15a
D28
EOT
Notes
Triplicate ECG at least one minute apart prior to 
C0D1 (Part 1) & C1D1 (Part 2) dose only.
Serious Adverse Event 
Assessment
All SAEs must be collected from the date of the participant’s written consent until 
100 days post discontinuation of dosing or participant’s participation in the study if 
the last scheduled visit occurs at a later time.
SAEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Adverse Events 
Assessment
Nonserious adverse events are collected from first dose through 100 days after last 
dose of study treatment
AEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Concomitant
Medication Use
X
X
X
X
X
Laboratory Tests
Hematology, Chemistry
X
X
X
X
X
There will be a -3 day window for collection of 
Hematology & Chemistry laboratory tests.
(See Section 9.4.4)
Thyroid Function Panel
X
X
X
X
Includes TSH, Free T3 and Free T4. There will 
be a -3 day window for the collection of Thyroid 
Function Panel. (See Section 9.4.4)
Pregnancy Test
(Serum or Urine)
X
X
X
WOCBP: Serum or urine pregnancy test must be
performed within 24 hours prior to 
administration of study treatment and on Day 1 
of each cycle regardless of dosing schedule. 
Pharmacokinetics
See Table 9.5.1-1 and Table 9.5.3-1
See Section 9.5.1 (Table 9.5.1-1) for 
MATE-renal transporter blood and urine 
samples to be collected.
See Section 6.3.1 for fasting requirements for PK 
sampling.
Biomarkers
See Table 9.5.1-1, Table 9.8-1, and Table 9.8-2
Revised Protocol No.: 06
Date: 05-Dec-2019
37
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-5:
On-treatment Procedural Outline - BMS-813160/Nivolumab (Arm C) - Parts 1 and 2 (Including Cross 
Over) [CV202103]
Part 1
Cycle 0
2-wk monotherapy
Part 1 and Part 2
Cycle 1 & Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D -1
D1
D2
D3
D7
D14
D1
D15a
D28
EOT
Notes
Immunogenicity
See Table 9.5.3-1
Mandatory On-
treatment Biopsy
X
X
X
Biopsy on C0D14 and C1D15 of Part 1 OR 
C1D28 of Part 2
Monotherapy should continue if biopsy is 
collected beyond C0D14; combination with 
nivolumab should only begin after the biopsy in 
Part 1.
Progression Driven 
Biopsy
At disease progression (see note)
Tissue submission is optional and biopsy is not 
required by protocol. 
Efficacy Assessments
Tumor Response
Assessment (CT/MRI)
To be performed every 8 weeks (± 1 week) from date of first dose.
The same modality that is selected at screening should be used for each 
assessment. Assessed by RECIST v1.1 criteria (see Appendix 5).
Study Treatment
BMS-813160
BMS-813160 is taken daily according to assigned dose.
Site to check participant’s pill diary at each visit
Nivolumab
X
Nivolumab infusion given over 30 minutes on 
Day 1 of each cycle
Note: In the event of multiple procedures are required at a single time point, the following is a list of procedures from highest priority to low: pharmacokinetic 
sampling, ECG and vital signs, and laboratory tests.
Abbreviations: C0D1 = Cycle 0, Day 1; C0D14 = Cycle 0, Day 14; C1D1 = Cycle 1, Day 1;C1D15 = Cycle 1, Day 15; C1D28 = Cycle 1, Day 28; CT = computed 
tomography; D -1 = Day -1; D1 = Day 1; D14 = Day 14; D15 = Day 15; D2 = Day 2; D28 = Day 28; D3 = Day 3; D7 = Day 7; ECG = electrocardiogram; ECOG
= Eastern Cooperative Oncology Group; EOT = end of treatment; IRT = Interactive Response Technologies; MATE = multidrug and toxin extrusion protein; 
MRI = magnetic resonance imaging; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; T3 = triiodothyronine; T4 = 
thyroxine; TSH = thyroid stimulating hormone; wk(s) = week(s); WOCBP = women of child bearing potential
a After 4 cycles, Day 15 visits are optional if the participant is tolerating study treatment well.
Revised Protocol No.: 06
Date: 05-Dec-2019
38
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-6:
On-treatment Procedural Outline - BMS-813160 Monotherapy (Arm D) - Part 2 only (CV202103)
Cycle 1 to 4
(4 wks/cycle) ± 3 days
Cycle 5 and
Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D1
D15
C1D28
D1
EOT
Notes
Eligibility Assessments
Inclusion/Exclusion 
Criteria
X
Participants must meet all eligibility criteria before 
starting treatment.
Utilize IRT
X
X
X
X
For all participants at Cycle 1 Day 1, each 
subsequent dosing visit and to discontinue 
participant (EOT)
Safety Assessments
Physical Examination
X
X
X
X
C1D1: Perform a complete physical examination 
on Day 1 of each cycle within 24 hours of dose 
administration.
On subsequent visits in each cycle, perform a 
symptom-directed physical examination within 
24 hours of dose administration.
Vital Signs
X
X
X
X
Including weight, body temperature, respiratory 
rate, pulse oximetry, seated blood pressure and 
heart rate.
Approximately the same time as the ECG. On 
days when there is a pre-dose and 2 hour 
post-dose ECG, vital signs except weight should 
be taken at the time of each ECG.
ECOG Assessment
X
X
X
X
12-Lead ECG
X
X
X
X
ECGs should be recorded after the participant has 
been supine for at least 5 minutes.
ECG prior to and 2 hours post BMS-813160 
administration for Cycles 1 and 2. Only pre-dose 
ECG will be obtained for subsequent cycles.
Revised Protocol No.: 06
Date: 05-Dec-2019
39
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-6:
On-treatment Procedural Outline - BMS-813160 Monotherapy (Arm D) - Part 2 only (CV202103)
Cycle 1 to 4
(4 wks/cycle) ± 3 days
Cycle 5 and
Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D1
D15
C1D28
D1
EOT
Notes
Triplicate ECG at least one minute apart prior to 
C1D1 dose only.
Serious Adverse Event 
Assessment
All SAEs must be collected from the date of the participant’s written consent until 
30 days post discontinuation of dosing or participant’s participation in the study if 
the last scheduled visit occurs at a later time.
SAEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Adverse Events 
Assessment
Nonserious adverse events are collected from first dose through 30 days after last 
dose of study treatment
AEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Concomitant
Medication Use
X
X
X
X
Laboratory Tests
Hematology, Chemistry
X
X
X
X
There will be a -3 day window for collection of 
Hematology & Chemistry laboratory tests.
(See Section 9.4.4)
Thyroid Function Panel
X
X
X
Includes TSH, Free T3 and Free T4. There will be 
a -3 day window for collection of Thyroid 
Function Panel. (See Section 9.4.4)
Pregnancy Test
(Serum or Urine)
X
X
X
WOCBP: Serum or urine pregnancy test must be 
performed within 24 hours prior to administration 
of study treatment and on Day 1 of each cycle
regardless of dosing schedule.
Pharmacokinetics
See Table 9.5.3-1
Biomarkers
See Table 9.8-1 and Table 9.8-2
Mandatory On-treatment 
Biopsy
X
Revised Protocol No.: 06
Date: 05-Dec-2019
40
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-6:
On-treatment Procedural Outline - BMS-813160 Monotherapy (Arm D) - Part 2 only (CV202103)
Cycle 1 to 4
(4 wks/cycle) ± 3 days
Cycle 5 and
Subsequent Cycles
(4 wks/cycle) ± 3 days
Procedure
D1
D15
C1D28
D1
EOT
Notes
Progression Driven 
Biopsy
At disease progression (see note)
Tissue submission is optional and biopsy is not
required by protocol.
Efficacy Assessments
Tumor Response
Assessment (CT/MRI)
To be performed every 8 weeks (± 1 week) from date of first dose.
The same modality that is selected at screening should be used for each 
assessment. Assessed by RECIST v1.1 criteria (see Appendix 5).
Study Treatment
BMS-813160
BMS-813160 is taken daily according to assigned dose.
Site to check participant’s pill diary at each visit
Note: In the event of multiple procedures are required at a single time point, the following is a list of procedures from highest priority to low: pharmacokinetic 
sampling, ECG and vital signs, and laboratory tests.
Abbreviations: C1D1= Cycle 1, Day 1; C1D28= Cycle 1, Day 28; CT = computed tomography; D1 = Day 1; D15 = Day 15; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; EOT = end of treatment; IRT = Interactive Response Technologies; MRI = magnetic resonance imaging; RECIST = 
Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; wks 
= weeks; WOCBP = women of child bearing potential
Revised Protocol No.: 06
Date: 05-Dec-2019
41
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-7:
Follow-up Procedural Outline (CV202103)
Procedure
Safety Follow-up
Notes
Cross-Over
Follow-up
30 Daysa
(± 7 Days)
FU 1
30 Daysb
(± 7 Days)
FU 2
60 Daysc
(± 7 Days)
FU 3
100 Daysc
(± 7 Days)
Survival
Follow-upd
(Q12W)
Safety Assessments
Physical Examination
X
X
X
X
Vital Signs and Weight
X
X
X
X
Including weight, body temperature, respiratory rate, 
pulse oximetry, seated blood pressure and heart rate.
ECOG Status
X
X
X
X
Review of Concomitant
Medications
X
X
X
X
Laboratory Tests
Hematology and Serum 
Chemistry
X
X
X
X
Pregnancy Test (Serum or 
Urine)
X
X
X
For WOCBP only.
12-Lead ECG
X
X
X
X
ECGs should be recorded after the participant has 
been supine for at least 5 minutes.
Adverse Event 
Reporting
AEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Monitor for Nonserious 
AEs
X
X
X
X
Nonserious AEs must be collected from first dose 
until 30 days (100 days for Arm C and Cohort 3b 
[Arm B, Part 2]) following the last dose of study 
treatment. All SAEs and AEs will be assessed using 
NCI CTCAE v4.03.
Monitor for SAEs
X
X
X
X
All SAEs must be collected from the date of the 
participant’s written consent until 30 days (100 days 
for Arm C and Cohort 3b [Arm B, Part 2]) post 
discontinuation of dosing or participant’s 
participation in the study if the last scheduled visit 
occurs at a later time. 
Revised Protocol No.: 06
Date: 05-Dec-2019
42
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2-7:
Follow-up Procedural Outline (CV202103)
Procedure
Safety Follow-up
Notes
Cross-Over
Follow-up
30 Daysa
(± 7 Days)
FU 1
30 Daysb
(± 7 Days)
FU 2
60 Daysc
(± 7 Days)
FU 3
100 Daysc
(± 7 Days)
Survival
Follow-upd
(Q12W)
All SAEs and AEs will be assessed using NCI 
CTCAE v4.03.
SAEs reported during this time period should be 
followed until resolved to baseline, stabilized or 
deemed irreversible.
Efficacy Assessments
Participants who discontinue study treatment for reasons 
other than progression of disease should continue tumor 
assessment every 8 weeks (± 1 week) until progression, 
meeting discontinuation criteria, or withdrawal of 
consent.
New Anti-cancer Therapy
X
X
X
X
X
New anti-cancer therapy including radiotherapy, 
surgery, and systemic therapy
Assessment of Participant 
Survival Status
X
Subject status will be assessed by either a clinic visit 
or telephone contact.
Abbreviations: AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; EOT = end of treatment; FU = follow-up; NCI = National Cancer Institute; Q12W = every 12 weeks; SAE = serious adverse event; WOCBP 
= women of child bearing potential.
a Cross-over follow-up visit applies only to participants planning to cross over to Arm C.
b FU 1 should only be used by participants who will not receive additional study treatment on protocol CV202103, including after completion of cross-over 
treatment.
c Arm C and Cohort 3b [Arm B, Part 2] only
d All participants begin after completion of safety follow-up every 12 weeks (± 2 weeks) until 2 years after last dose of study treatment.
Revised Protocol No.: 06
Date: 05-Dec-2019
43
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
3
INTRODUCTION
This is a first-in-oncology study of BMS-813160, a dual antagonist of cysteine-cysteine (C-C) 
chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) in participants with 
advanced solid tumors. This study will evaluate the safety profile, tolerability, pharmacokinetics 
(PK), pharmacodynamics, and preliminary efficacy of BMS-813160 in combination with either 
chemotherapy or nivolumab or chemotherapy plus nivolumab in participants with metastatic 
colorectal cancer (CRC) and pancreatic cancer. The study will be conducted in 2 parts. Part 1 will 
evaluate safety, tolerability, PK, and pharmacodynamics of different doses of BMS-813160 in 
combination with either FOLFIRI (Arm A), gemcitabine (Gem)/ nab-paclitaxel (ABRAXANE) 
(Arm B), or nivolumab (Arm C) in participants with advanced colorectal and pancreatic cancers. 
Part 2 is a dose expansion study to assess preliminary efficacy of BMS-813160 alone (Arm D) or 
in combination with either chemotherapy or nivolumab or chemotherapy plus nivolumab in 
participants with advanced CRC or pancreatic cancer.
3.1
Study Rationale
3.1.1
Rationale for Inhibiting CCR2/5 in Cancer
Immuno-oncology, which harnesses the immune system to fight cancer, has emerged as a major 
advancement in cancer treatment. Current approaches include blocking immunosuppressive 
signals with antagonistic antibodies and stimulating immunity with agonistic antibodies. Despite 
recent progress, many cancer types, including pancreatic cancer and CRC, have been resistant to 
the current immune approaches. Thus, new approaches targeting different immune mechanisms 
are needed to overcome the resistance to current immune therapies. Blocking both CCR2 and 
CCR5 with a small-molecule antagonist represents 1 such new approach with the potential to 
extend immuno-oncology benefits to patients not adequately served by existing therapies.
Patho-biologically, cancer progression exploits an evolving interplay among different cell types 
within the tumor microenvironment (TME). In addition to cancer cells, immune cell types, 
especially myeloid cells and T-regulatory (Tregs) cells, accumulate during cancer progression. The 
accumulation of both cell types is mediated by chemokine receptors interacting with their ligands 
(chemokines), which drives the migration and infiltration of these immune cell types into the TME. 
Of these chemokine receptors, CCR2 and CCR5 have been shown to be key drivers of the 
migration and accumulation of myeloid cells, including tumor-associated macrophages (TAMs), 
and myeloid-derived suppressor cells (MDSCs), into the TME. Moreover, both receptors have
been shown to be important players in the trafficking of Tregs to the TME. Besides its primary 
role in driving immune cell migration to the TME, CCR5 inhibition has been recently shown to 
repolarize TAMs from M2- to M1-like in the TME.
Chemokine (C-C motif) ligand 2 (CCL2) is secreted by tumors and recruits CCR2 positive 
inflammatory monocytes from the bone marrow to the TME where they transform to 
immuno-suppressive TAMs and prevent effective anti-tumor immunity. Previous studies have 
shown that the ratio of bone marrow to blood inflammatory monocytes is prognostic and inhibition 
of this axis showed responses in preclinical tumor models.1,2
Revised Protocol No.: 06
Date: 05-Dec-2019
44
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Similarly, chemokine (C-C motif) ligand 5 (CCL5) is produced by T cells at invasive margins of 
CRC liver metastasis. Its receptor CCR5 is found on tumor cells, TAM, and circulating Tregs, and 
plays a role in immune exploitation by tumor cells promoting tumor growth. CCR5 inhibition with 
maraviroc showed reduction in tumor promoting cytokines, tumor death in explant models and 
was prognostic for responses to chemotherapy.3,4
Since tumors leverage the CCL2-CCR2 and CCL5-CCR5 axis to promote tumor growth through 
Tregs and TAM, blocking of this axis may be able to overcome the immunosuppressive TME and 
promote effective anti-tumor immunity.
3.1.2
Rationale for Selecting Patients with Pancreatic and Colorectal Cancers 
and Combining with Chemotherapy
The CCR2/CCL2 axis, considered important in mediating myeloid and Treg cell migration to the 
TME, is preclinically validated in multiple tumor types including pancreatic cancer and CRC.1,5
CCR5/CCL3 and CCL5, also important in mediating myeloid and Treg cell migration to the TME 
as well as TAM repolarization within the TME, are also preclinically validated in multiple tumor 
types, including pancreatic cancer and CRC. TAMs and MDSCs in the TME may also mediate 
chemotherapy resistance.
Recent clinical data supports targeting CCR2 to reverse the immunosuppressive TME in pancreatic 
cancer. Nywening et al evaluated the clinical activity of the combination of PF-04136309, a small 
molecule antagonist of CCR2, with FOLFIRINOX chemotherapy in the treatment of borderline 
resectable or locally advanced (ie, first-line [1L]) pancreatic cancer.6 Of 39 patients treated, 
32 achieved local tumor control and 16 of 33 evaluable patients (49%) achieved an objective tumor 
response, which was greater than the prior expectation of 25% objective response rate (ORR). 
There was increase in CCR2 positive inflammatory monocytes in the bone marrow and decrease 
in CCR2 positive inflammatory monocytes in the peripheral blood of patients treated with the 
combination of CCR2 inhibitor and FOLFIRINOX. This was reversed in patients treated with 
FOLFIRINOX alone. Quantitative polymerase chain reaction (PCR) of patients’ tumor showed an 
increase in immuno-stimulating and a decrease in immunosuppressive gene expression profiles
with the combination of CCR2 inhibitor and chemotherapy compared with chemotherapy alone. 
In 6 patients with paired tumor biopsies, there was a decrease from baseline in TAM, an increase 
in CD4+ and CD8+ T cells, and a sharp decrease in the fraction of CD4+ T cells with a Treg 
phenotype following treatment with FOLFIRINOX and CCR2 inhibitor. Although preliminary, 
these results support further study of CCR2 inhibition in combination with chemotherapy in 
pancreatic cancer.
Similarly, CCR5 has been targeted in the treatment of CRC. Halama et al employed maraviroc, a 
small-molecule antagonist of CCR5, in the treatment of patients with treatment refractory CRC
after 2 to 7 previous lines of treatment.4 On paired biopsies during maraviroc monotherapy 
treatment, reduced tumor cell proliferation and increased tumor cell death were seen, along with a 
variety of immune changes consistent with increased anti-tumor immunity. Specifically, inhibition 
of CCR5 in patient-derived explant models showed decrease in tumor promoting cytokines, 
selective tumor death and repolarization of TAMs. In addition, 5 of the patients also received 
Revised Protocol No.: 06
Date: 05-Dec-2019
45
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
maraviroc in combination with (previously received) chemotherapy. In these patients, 3 (60%) 
achieved an objective partial response (PR), which was unexpected given the multiple lines of 
previous therapy.
Given the clinical data with CCR2 and CCR5 antagonism individually in cancer, the potential 
exists that dual CCR2/5 targeting in combination with chemotherapy may lead to even greater 
benefit. Inhibition of the tumor promoting effects of CCR2 and CCR5 signaling in the TME may 
work synergistically with chemotherapy and the lack of overlapping toxicity with chemotherapy 
also supports combining chemotherapy with CCR2/5 inhibitor.
3.1.3
Rationale for the Chemotherapy Regimens in Arms A and B
Treatment options for patients with mCRC are predominantly 5-fluorouracil (5-FU) and 
leucovorin-containing regimens in combination with either oxaliplatin or irinotecan (FOLFOX or 
FOLFIRI) with a biologic agent such as bevacizumab. Epidermal growth factor receptor (EGFR)
antibodies, cetuximab or panitumumab, are an option if RAS status is non-mutated. Both regimens 
are considered to be equivalent, with a 1L median progression-free survival (PFS) of 8.5 months 
for FOLFIRI and 8 months for FOLFOX.7 Switching from FOLFOX to FOLFIRI in second line 
(2L) and vice versa showed no difference in survival in metastatic CRC with median overall 
survival (OS) of 21.5 months vs 20.6 months.7 FOLFIRI is being used in this trial as 2L 
chemotherapy in CRC to avoid any potential drug-drug interaction (DDI) between BMS-813160 
and oxaliplatin. 
The choice of biologic is selected based on individual patient characteristics (RAS status, 
sidedness of tumor, and contraindications to the therapy), patient preferences (avoiding rash or 
diarrhea withe EGFR antibodies), and physician preference. In a Phase 3 trial of KRAS wild-type 
CRC patients, there was no difference in response rate, PFS,
or OS in the 
cetuximab + chemotherapy group vs bevacizumab + chemotherapy group.8 Continuation of 
bevacizumab with switch in chemotherapy showed improved OS in 2 pivotal studies in metastatic 
CRC.9,10 Therefore, bevacizumab or its biosimilar can be added to 2L FOLFIRI if it is appropriate 
and available locally as part of standard of care, and will be administered in accordance with local 
Health Authority approved labeling.
Treatment options for patients with metastatic pancreatic cancer are limited. Gemcitabine 
combined with nab-paclitaxel is a United States (US) Food and Drug Administration (FDA) 
approved 1L treatment for patients with advanced pancreatic cancers.11 This regimen showed a 
median PFS of 5.5 months and a median OS of 8.5 months and is the predominantly used regimen 
in metastatic pancreatic cancer.
3.1.4
Rationale for Selecting 2L CRC in Part 2 Arm A
Reported ORR with chemotherapy and biologic in 1L CRC vary widely from 45 to 65%.12 The 
response rate can also vary significantly between vascular endothelial growth factor (VEGF)
antibodies and EGFR antibodies when combined with chemotherapy. As the primary endpoint of 
the trial is response rate, 2L CRC was selected to test the response rate with FOLFIRI in 
combination with BMS-813160 in a homogenous patient population. Adding bevacizumab to 2L 
Revised Protocol No.: 06
Date: 05-Dec-2019
46
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
chemotherapy did not show any difference in response rates in spite of improved OS.9 The 
outcomes in 2L CRC patients with chemotherapy is generally poor with ORR of less than 20%,
justifying the addition of an investigational agent to chemotherapy in an effort to improve patient 
outcomes in 2L CRC.
3.1.5
Rationale for Combining BMS-813160 with Nivolumab in Patients with 
Advanced Pancreatic and Colorectal Cancers in Arm C
Patients with advanced pancreatic cancer can be treated with 5-FU/liposomal irinotecan in the 2L
setting and patients with advanced CRC are treated with regorafenib or trifluridine/tipiracil in the 
third-line (3L) setting. However, outcomes with these agents are generally poor with low ORR, a 
median PFS of only 2 to 3 months, and median OS of 6 to 7 months.13,14,15 These regimens also 
have significant toxicity and additional options are clearly needed in advanced pancreatic and 
colorectal cancers. Development of newer and novel agents in the treatment of these diseases 
resistant to chemotherapy is an area of unmet need.
Anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy has no 
clinical activity in microsatellite stable (MSS) CRC or in pancreatic cancer.16,17 This is likely due 
to the immunosuppressive effects of Tregs and MDSCs in TME leading to immune escape 
mechanisms.18 Combination of anti-PD-1 agents with drugs that mitigate the immunosuppressive 
TME may offer therapeutic potential.19 Recent data showed clinical responses in MSS CRC to a 
combination of a MEK inhibitor with a PD-L1 antibody suggesting that novel combinations have 
the potential for showing responses in this patient population, which has traditionally been resistant 
to checkpoint blockade alone.20 The immune effects on the TME seen with targeting the CCR2/5 
pathways suggest that combination with other immune agents such as nivolumab, a monoclonal 
antibody that blocks the PD-1 pathway and activates T cells, may provide additional benefit. Thus, 
this initial cancer trial of BMS-813160 will also study a combination of BMS-813160 with 
nivolumab in participants with advanced CRC or pancreatic cancer.
Both CCR2 and CCR5 mediate infiltration and immune suppression of tumor-associated myeloid 
cells and regulatory T cells, while PD-1 restrains effector T cell function in the TME. It is thus 
hypothesized that targeting both CCR2/CCR5 and PD-1 pathways will provide at least additive 
anti-tumor activities. Recent preclinical studies have shown that combination of a CCR2/5-dual 
antagonist mouse surrogate, BMS-687681 with an anti-PD-1 mouse surrogate antibody, BMT-
144637, provides greater anti-tumor efficacy relative to either agent alone, as measured by both 
reduction in tumor volume and the number of tumor-free mice. These 2 mouse surrogates, BMS-
687681 and BMT-144637, have comparable biological activities to BMS-813160 and nivolumab, 
respectively. For example, BMS-687681 potently blocks binding of MCP-1 to mouse CCR2-
expressing cells and mouse MIP-1- to mouse CCR5-expressing cells, potently inhibits mouse 
MCP-1- and mouse MIP-1β-induced functions (calcium flux, integrin CD11b upregulation), and 
is structurally related to BMS-813160. Both BMS-687681 (administered at up to 100 mg/kg PO 2 
times a day [BID] x 36 doses) and BMT-144637 (administered at up to 10 mg/kg x 3 doses), alone 
and in combination, were well tolerated; none of the treated mice showed any significant clinical 
signs of toxicity, including reductions in body weight, moribundity, or mortality; like the control 
Revised Protocol No.: 06
Date: 05-Dec-2019
47
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
and monotherapy groups, combination of BMS-687681 and anti-PD-1 did not significantly affect 
the body weight over the course of study. In summary, targeting both CCR2/5 and PD-1 provides 
enhanced anti-tumor efficacy and is well tolerated pre-clinically, thus supporting the proposed 
clinical study with combination of BMS-813160 and nivolumab.
3.1.6
Rationale for Testing Lower Dose of BMS-813160
The testing of lower doses of BMS-813160 is primarily based on the preclinical PK/efficacy 
findings with BMS-687681, a mouse surrogate for BMS-813160, in combination with anti-PD-1 
mouse surrogate, in tumor models. BMS-813160 is not suitable for in vivo efficacy studies due to 
its weak mouse potency for CCR2/5 as well as its poor mouse PK. 
Dose-efficacy studies with BMS-687681 in combination with anti-PD-1 mouse surrogate in 3 
different syngeneic mouse tumor models have shown robust synergistic efficacy against tumor 
progression with a plasma trough concentration ranging from 0.1 to 3-fold 90% inhibition 
concentration (IC90) for inhibiting CCR2/5 function. Moreover, BMS-687681 doses that provide 
a plasma trough concentration of 0.3 to 0.5-fold IC90 for inhibiting CCR2/5 function offer the 
most durable anti-tumor efficacy following both first tumor cell challenge and re-challenge, 
whereas those of > 3-fold IC90 result in significantly less efficacy. Therefore, testing lower doses 
of BMS-813160 will help further characterize the PK, pharmacodynamics, and preliminary 
efficacy of lower doses of BMS-813160.
3.1.7
Rationale for Testing BMS-813160 in Combination with Nivolumab, 
Gemcitabine, and Nab-Paclitaxel
Data from recent studies have shown benefit of combining chemotherapy and immunotherapy.21,22
Cell death with chemotherapy has shown to release tumor antigens that prime the immune system, 
and decrease MDSCs and Tregs.22 The combination of chemotherapy and anti-PD-1 agents have 
shown improved response rates, PFS, and OS when compared with chemotherapy alone in 1L lung 
cancer.23,24 Pre-clinical and clinical studies show activity of CCR2 and CCR5 inhibitors in 
combination with anti-PD-1 agents and chemotherapy, respectively. Please see Section 3.1.2 for 
rationale combining BMS-813160 with chemotherapy and Section 3.1.5 for rationale combining 
BMS-813160 with anti-PD-1 agents.
All agents to be used in the proposed combination have shown well-defined toxicity profiles based 
on a safety database comprised of participants treated with either monotherapy or combinations 
across multiple tumor types. Combination of nivolumab with Gem/nab-paclitaxel in 1L pancreatic 
cancer has been shown to be safe in a Phase 1/2 study.25,26 In this study, 50 participants with 
previously untreated pancreatic cancer were treated with nivolumab in combination with 
Gem/nab-paclitaxel. There was 1 dose-limiting toxicity (DLT) of Grade 3 non-immune hepatitis 
attributed to gemcitabine and the participant was able to continue on treatment with nivolumab 
and nab-paclitaxel without any further episodes of hepatitis. The most common (>10%) Grade 3 
or higher adverse events (AEs) were anemia (36%), neutropenia (36%), gastrointestinal events 
(24%), hepatic toxicity (22%), peripheral neuropathy (16%), thrombocytopenia (12%), and colitis 
(12%). Respiratory failure (most likely pneumonitis) was the only Grade 5 AE. Of the 42 evaluable 
Revised Protocol No.: 06
Date: 05-Dec-2019
48
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
participants, 1 had a complete response (CR), 8 had a PR, and 23 had stable disease (SD), which 
was encouraging for anti-tumor activity. 
Evaluation of BMS-813160 in combination with Gem/nab-paclitaxel (Part 1, Arm B) and in 
combination with nivolumab (Part 1, Arm C) is ongoing in the current study. Based on the data 
available, the safety profile of BMS-813160 is manageable with either the 300 mg BID or 600 mg 
once per day (QD) dose in combination with gemcitabine and nab-paclitaxel or nivolumab. Please 
refer to Section 3.2.1.4 and the current BMS-813160 Investigator’s Brochure (IB)27 for further 
details.
Therefore, a cohort of participants will be treated with the combination of chemotherapy, 
nivolumab, and BMS-813160 to evaluate safety and preliminary efficacy of this combination. 
Please see Sections 3.3 and 5.1.3 for further details.
3.1.8
Rationale for Exploring Monotherapy in Arm D
Recent data showed clinical activity of CCR5 inhibitor maraviroc as monotherapy in advanced 
colorectal cancer.4,28 Anti-PD-1 agents did not show any activity in MSS CRC or pancreatic cancer 
and any activity seen with the combination could be from BMS-813160 alone.16,17 In this regard, 
if the BMS-813160 in combination with nivolumab arm (Arm C) shows an ORR of approximately 
15% or durable responses (defined as a continuous response [objective CR or PR] beginning within 
12 months of treatment and lasting ≥6 months) are seen with the combination, the Sponsor will 
open Arm D to explore efficacy of BMS-813160 as a single agent. 
3.2
Background
3.2.1
BMS-813160
CCR2 and CCR5 are 2 chemokine receptors that are expressed on myeloid cell and T cell infiltrates 
in the TME. Each receptor has been separately shown to be an important player in multiple models 
of cancer, including pancreatic cancer and CRC. Therefore, targeting both receptors with a small-
molecule dual antagonist is a potential novel treatment for cancer where compelling evidence 
supports that myeloid and Treg play a key role in mediating immune suppression within the TME.
3.2.1.1
Nonclinical Pharmacology of BMS-813160
BMS-813160 is an equipotent dual antagonist of CCR2 and CCR5 that binds potently to both 
receptors and exhibits potent dual inhibition of in vitro receptor-mediated functions, including 
chemotaxis, calcium flux, non-hydrolyzable guanosine triphosphate analog (guanosine 5’-3-O-
[thio]triphosphate) [GTP-γS] exchange, and Mac-1 (integrin α) [CD11b] upregulation, as well as 
CCR5 phosphorylation and internalization induced by ligand interaction. BMS-813160 is a full 
and reversible antagonist of both receptors and blocks CCR2- and CCR5-dependent functions in 
response to all known ligands. BMS-813160 is also at least 800-fold selective against a panel of 
other chemokine receptors (C-C chemokine receptor 1 [CCR1], C-C chemokine receptor 4 
[CCR4], C-X-C chemokine receptor 2 [CXCR2], C-X-C chemokine receptor 3 [CXCR3], and 
C-X-C chemokine receptor 5 [CXCR5]) and a panel of G protein-coupled receptors
(GPCRs)/transporters (21 targets).
Revised Protocol No.: 06
Date: 05-Dec-2019
49
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
In CCR2 pharmacodynamic models, BMS-813160 significantly reduced blood monocytes in 
human CCR2 knock-in (hCCR2 KI) mice and increased serum levels of monocyte chemotactic 
protein (MCP)-1 (ligand for CCR2) in hCCR2 KI mice and in monkeys at doses providing plasma
concentrations that are greater than or equal to the CCR2 binding concentration at which 
90% inhibition is observed (IC90). The compound also reduced blood monocytes in monkeys 
although the reduction was not statistically significant due to inter-animal variability. These data 
support the use of these 2 measurements, serum MCP-1 and absolute monocyte count, as CCR2 
PD biomarkers in studies of BMS-813160.
In CCR5 homeostatic models in the mouse, preliminary studies show that BMS-813160 robustly 
inhibited ex vivo-stimulated whole blood CD11b upregulation at doses providing plasma 
concentrations that are greater than or equal to the mouse CCR5 binding / CD11b IC90. When 
tested in naïve monkeys for its effect on CCR5 phosphorylation with or without ex vivo stimulation 
and CCR5 internalization with ex vivo stimulus, BMS-813160 significantly inhibited 
phosphorylation and internalization at plasma concentrations greater than or equal to the IC90 of 
CCR5. 
When studied in 48-hour thioglycollate (TG) peritonitis model using hCCR2 KI mice, 
BMS-813160 substantially reduced monocyte/macrophage influx into the peritoneal cavity, 
providing an estimated in vivo free plasma concentration required to yield 50% of the maximal 
response (EC50) value of 4.9 nM, which correlated well with the in vitro binding 50% inhibition 
concentration (IC50) of 5.8 nM (mouse binding to human peripheral blood mononuclear cells 
[hPBMCs]). Maximal inhibition of monocyte/macrophage infiltration was achieved with 
approximately 98% receptor occupancy.
Additional details are provided in the current version of the IB.27
3.2.1.2
Nonclinical Pharmacokinetics and Metabolism of BMS-813160
Pharmacokinetic studies indicated that BMS-813160 was orally bioavailable (63 to 100%) in mice, 
rats, dogs, and monkeys. BMS-813160 exhibited a high volume of distribution at steady state 
(Vss), low serum protein binding in human and animal species, with a moderate (dogs and 
monkeys) to high (rodents) clearance rate. BMS-813160 and BMS-939429, a t-butyl hydroxylated 
metabolite, were found to be substrates for active liver uptake; however, the uptake does not appear 
to be governed by organic anion transporting polypeptide (OATP) or sodium-taurocholate 
cotransporting polypeptide (NTCP) transporters, and so is likely to occur via other hepatic uptake 
transporters (preliminary data).
The metabolic profiles of BMS-813160 were similar across species. Sixteen metabolites of 
BMS-813160 were observed in nonclinical in vitro and in vivo studies. Formation of 
BMS-939429, a t-butyl hydroxylated metabolite, represented a prominent metabolic pathway in 
all species studied. Additional biotransformation routes included other mono-oxidations or 
hydroxylation, oxidative deamination (N-dealkylation), glucuronidation of a hydroxylated 
metabolite, and combinations of multiple oxidative reactions. No unique metabolites were detected 
in human-derived in vitro systems. Metabolite profiling of steady-state plasma samples from 
mouse, rat, monkey, and human suggested that BMS-813160 was the major drug-related 
Revised Protocol No.: 06
Date: 05-Dec-2019
50
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
component and BMS-939429 was the most prominent metabolite in the circulation in all species. 
In vitro receptor binding studies suggested that BMS-939429 was ≥15x and ≥50x less potent than 
the parent compound towards the CCR2 and CCR5 receptors, respectively, suggesting that the 
major metabolite is not likely to contribute substantially to the pharmacology of BMS-813160. In 
rat, monkey, and human, BMS-813160 was cleared by multiple pathways, including metabolism, 
direct urinary and biliary/fecal excretion. In humans, renal clearance (CLR) of BMS-813160 was 
greater than the glomerular filtration rate (GFR), indicating active renal secretion, however, the 
specific transporter(s) involved in the renal secretion have not been identified.
In vitro, the metabolism of BMS-813160 was primarily mediated via cytochrome P450 (CYP) 
3A4, with some contribution from CYP3A5, and BMS-813160 was also a substrate for 
P glycoprotein (P-gp). Based on these results, the potential exists for a DDI if BMS-813160 is 
co-administered with inhibitors or inducers of CYP3A or P-gp. BMS-813160 and its hydroxylated 
metabolite (BMS-939429) did not inhibit CYP enzymes (IC50 > 40 μM) in human liver 
microsomes (HLM) and BMS-813160 and BMS-939429 showed low potential to inhibit uridine 
5'-diphospho-glucuronosyltransferase (UGT) 1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 
at concentrations up to 100 μM (preliminary data). BMS-813160 also did not induce CYP1A2, 
CYP2B6, or CYP3A4/5 in primary human hepatocytes; therefore, BMS-813160 is not expected 
to alter the clearance of compounds that are CYP, UGT, or P-gp substrates. BMS-813160 was not
a substrate of human transporters OATP1B1, OATP1B3, NTCP, BCRP, OAT1, OAT3, OCT2, 
multidrug and toxin extrusion protein 1 (MATE1), and MATE2-K. BMS-813160 and 
BMS-939429 are unlikely to inhibit BCRP, P-gp, OAT1, OAT3, NTCP, BSEP, MRP2, OATP1B1, 
OATP1B3, OCT2, and MATE2-K. However, BMS-813160 and BMS-939429 inhibited MATE1 
with IC50 values of 4.6 and 32.1 μM, respectively. Refer to Section 5.4.5 for rationale for 
collection of biomarkers to evaluate potential for MATE1 inhibition by BMS-813160, and 
Sections 7.7.1 and 7.7.2 for restrictions on co-medications.
Additional details are provided in the BMS-813160 IB.27
3.2.1.3
Clinical Pharmacokinetics of BMS-813160
Single dose PK of BMS-813160 was evaluated in 48 healthy participants over a dose range of 
5 mg to 2000 mg (Study CV20200129). The median time of maximum observed concentration 
(Tmax) of BMS-813160 was between 2.5 and 3 hours for doses up to 60 mg and decreased at doses 
≥150 mg, ranging from 0.5 to 1.8 hours. The plasma apparent terminal phase half life (T-HALF)
was consistent across the dose groups that had a well-characterized terminal phase (ie, 60 mg to 
2000 mg) and ranged from 12 to 18 hours. The fitted power models suggest that the single dose 
PK parameters of BMS-813160 deviate from dose proportionality (ie, the exposure increases were 
higher than dose proportional). Renal CLR of BMS-813160 did not appear to change with BMS-
813160 dose, while the amount of BMS-813160 excreted in urine as measured by %UR increased 
with dose. BMS-813160 CLT/F decreased with increasing dose and since T-HALF and CLR 
appeared similar across doses, this suggests a constant clearance with a changing oral 
bioavailability (F). Together, these data are consistent with a dose-related increase in oral 
bioavailability of BMS-813160 with increasing dose.
Revised Protocol No.: 06
Date: 05-Dec-2019
51
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
After giving a group of participants (n = 6) 150 mg [14C]BMS-813160, a total of 81.5% of the 
administered radiolabeled dose was recovered as [14C]: the majority in feces (58.7%) and the 
remaining amount in urine (22.8%). BMS-813160 was the predominant drug-related component 
in the plasma, and BMS-939429 was a prominent metabolite, accounting for 53 and 30% of total 
[14C]. The parent drug, together with selected metabolites that were quantified with an exploratory 
liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, comprised approximately 
87% of the circulating radioactivity.
Multiple dose PK of BMS-813160 was evaluated in 42 participants over a dose range of 10 mg to 
300 mg QD (n = 24) and 300 mg to 900 mg BID (n = 18) for 14 days (Study CV20200230). The 
increases in systemic exposures of BMS-813160 were generally greater than dose proportional 
within the QD and BID dose panels. The last dose (Day 14) mean terminal phase half-life values 
in this study (~12 to 16 hours) were consistent with the observed time to steady-state (3 to 5 days 
for QD dosing and generally within 3 days for BID dosing) and the observed accumulation ratios 
(up to 1.5 for QD panels and up to 1.7 for BID panels). Approximately 10% to 22% (QD) and 
23% to 39% (BID) of the orally administered dose of BMS-813160 was recovered in urine as 
unchanged BMS-813160. The renal CLR of both BMS-813160 and BMS-939429 were greater 
than GFR, indicating net tubular secretion of both analytes. Based on the first-dose PK relative to 
steady-state PK, no time dependency in BMS-813160 PK was observed at any dose or either 
regimen studied. Steady-state systemic exposures of BMS-939429 were less than 50% those of 
parent BMS-813160.
Relative bioavailability study (Study CV202005,31 N=12) showed that there was no meaningful 
formulation effect in healthy participants in this study. The relative bioavailability of BMS-813160 
administered as a single 300 mg (6 x 50 mg) oral dose in capsules was very similar to that from a 
300 mg oral dose in solution. The study also examined the effect of food on the capsule 
formulation. There was a modest effect, with consumption of a high-fat meal, on the systemic 
exposure of BMS-813160 administered in the capsule formulation. Administration of a 300-mg 
dose of BMS-813160 in capsule form to participants fed a high-fat, high-calorie meal resulted in 
a 45% decrease in maximum concentration (Cmax) and a 16% decrease in AUC(0-T) and 
AUC(INF). It is likely that this effect would be diminished in the presence of a meal of more 
normal content. Thus, lacking a substantial food effect, administration of BMS-813160 in solid 
formulations regardless of the fed/fasting status of participants may be a viable approach.
Preliminary PK evaluation in participants with advanced solid tumors receiving 300 mg BID or 
600 mg QD monotherapy dose (Study CV202103) showed PK of BMS-813160 in cancer patients
are consistent with previous results in healthy subjects, with slightly greater inter-subject 
variability. The median Tmax at steady-state (Day 14) ranged from 2 to 3 hours for 300 mg BID 
and from 1 to 3 hours for 600 mg QD. The geometric mean (CV%) Cmax at steady-state are 
767 (68) ng/mL and 2290 (57) ng/mL for 300 mg BID and 600 mg QD, respectively. AUC(0-24) 
at steady-state are 8184 (70.3) ng•h/mL and 11975 (47) ng•h/mL for 300 mg BID and 600 mg QD, 
respectively. The geometric mean (CV%) accumulation ratio based on AUC(0-24) between Day 1 
and Day 14 was estimated to be 1.55 (50) for 300 mg BID and 1.50 (36) for 600 mg QD. Based 
Revised Protocol No.: 06
Date: 05-Dec-2019
52
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
on preliminary monotherapy data from oncology study (CV202103), there was no consistent 
difference in PK parameters between tested tumor types (or arms). Please refer to the IB27 for 
further details.
3.2.1.4
Clinical Safety of BMS-813160
BMS-813160 was previously evaluated and found to be relatively safe and well tolerated in both 
healthy participant studies and in participants with diabetic kidney disease (DKD). To date, 
BMS-813160 has been studied in more than 5 clinical trials. Altogether, more than 390 participants 
have received at least 1 dose of BMS-813160 (108 healthy participants; 59 participants with DKD; 
more than 243 participants with advanced cancer).
Healthy Participants
In the single ascending dose (SAD) study CV202001, BMS-813160 was safe after single dose 
administrations up to 2,000 mg in healthy participants.29 There were no deaths, serious adverse 
events (SAEs) or discontinuations due to AEs. All reported AEs were mild in intensity. At the 
2,000 mg dose there was an increased incidence of central nervous system (CNS)-related AEs 
(dizziness and euphoric mood). Dizziness occurred in 5 participants (7.1%), all receiving BMS-
813160, and all but 1 was considered by the investigator to be related to study drug (n = 1 each in 
the 150 mg and 1,200 mg groups, and n = 3 in the 2000 mg group). There were 2 participants in 
the 2,000 mg BMS-813160 group and 1 participant in the placebo group who had AEs of euphoria.
In the multiple ascending dose study CV202002, multiple doses of BMS-813160 were safe and 
generally well tolerated in healthy participants across the dose range of 10 to 300 mg QD (n = 24) 
and 300 to 900 mg BID (n = 18) for 14 days.30 There were no deaths, SAEs, or discontinuations 
due to AEs in this study. AEs were reported by 17 participants (40.5%) receiving any dose of 
BMS-813160 and in 3 participants (21.4%) receiving placebo. There was no apparent dose 
relationship with respect to AEs. One AE of headache in a participant receiving BMS-813160 
10 mg QD was considered moderate in intensity. All other AEs were considered to be mild in 
intensity. There were concentration-dependent increases in QRS and PR intervals and heart rate at 
600 mg BID and 900 mg BID, without any electrocardiogram (ECG)-related AEs or clinical 
sequalae. The increases in PR (mean < 16 msec at peak), QRS (mean < ~10 msec at peak), and 
heart rate (< ~10 bpm at peak) were not considered clinically significant. Concentration-response 
assessment showed no QTc prolongation.
Participants with Diabetic Kidney Disease
BMS-813160 was generally safe and well-tolerated when administered for 12 weeks to 
participants with DKD; 88 participants received BMS-813160 150 mg QD (n = 29), BMS-813160 
300 mg BID (n = 30), or placebo (n = 29). AEs were reported for 43 (48.9%) of the 88 treated 
participants, with the most frequently reported AEs being edema peripheral (6.8% of participants), 
fatigue (5.7% of participants), diarrhea (3.4% of participants), headache (3.4% of participants), 
and back pain (3.4% of participants). There were no marked differences in AE frequencies in 
participants receiving BMS-813160 (any dose) compared with placebo, and no dose-related trends 
were apparent in the frequency of any AEs. The majority of AEs were mild or moderate in severity. 
Revised Protocol No.: 06
Date: 05-Dec-2019
53
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Seven participants had on-treatment SAEs, but only 1 SAE (lobar pneumonia) was assessed as 
related to treatment; this event resolved with study treatment interruption and medical treatment, 
and the participant resumed study treatment and completed the treatment period. PR intervals 
> 200 msec appeared to be more frequent in the drug-treated participants (300 mg BID, 8 of 
30 participants [26.7%], 150 mg QD, 8 of 29 participants [27.6%]) compared with placebo (4 of 
29 participants [13.8%]), although the apparent difference does not take into account changes from 
baseline, including baseline values that were > 200 msec. QRS intervals > 120 msec were similar 
to placebo (10% of each group). QTcF intervals > 450 msec were similar between the groups, 
although there were numerically more > 30 msec changes from baseline in the drug-treated groups 
(150 mg QD, 4 of 29 participants [13.8%]; 300 mg BID, 3 of 30 participants [10%]) than in placebo 
(1 of 29 participants [3.4%]).
Participants with Advanced Colorectal and Pancreatic Cancers
Safety evaluation of BMS-813160 in advanced cancer patients with a 2-week monotherapy lead-in 
followed by combination with chemotherapy or nivolumab in Part 1 of Study CV202103 is 
complete. As of the data cutoff date of 30-Oct-2019 for the ongoing study CV202103, safety data 
are available for 243 participants who have received at least 1 dose of BMS-813160 (Part 1 Arm 
A [n = 18], Arm B [n = 21], Arm C [n = 36]; Part 2 Arm A [n = 44], Arm B [n = 76], Arm C 
[n = 48]). The safety profile of BMS-813160 is manageable with all doses tested. One DLT (Grade 
3 rash) was observed with BMS-813160 300 mg BID in combination with gemcitabine and nab-
paclitaxel, and 1 DLT (pericardial effusion with pericarditis) was observed with BMS-813160 
600 mg QD in combination with gemcitabine and nab-paclitaxel. Both of these participants have 
continued on the study treatment with 1 dose reduction in both study drug (BMS-813160 600 mg 
QD reduced to 300 mg QD) and chemotherapy (gemcitabine 1000 mg/m2 reduced to 800 mg/m2
and nab-paclitaxel 125 mg/m2 reduced to 100 mg/m2) and tolerated further treatment well. There 
were no DLTs in Part 2 Arm B Cohort 3b. Overall, the AE profile appears to be similar to expected 
frequency in these cancers when combined with chemotherapy or nivolumab. Please refer to the 
IB for further details.27
3.2.2
Nivolumab
Nivolumab is a fully human, immunoglobulin G4 (IgG4) [kappa] isotype monoclonal antibody 
that binds to PD-1 with nanomolar affinity (dissociation constant [Kd], 3.06 nM) and a high degree 
of specificity. Nivolumab blocks binding of PD-1 to its ligands PD-L1 and PD-L2. Nonclinical in 
vitro testing of nivolumab demonstrated that binding to PD-1 results in enhanced T-cell 
proliferation and release of interferon gamma (IFNγ) in vitro in mixed lymphocyte reaction and 
cytomegalovirus assays. 
The nonclinical safety of nivolumab was evaluated in a comprehensive toxicology program in 
mice and monkeys and was submitted as part of Biologics License Application 125527.32 Details 
of the in vitro and in vivo nonclinical pharmacology studies conducted to support the development 
of nivolumab can be found in Section 4.1 of the nivolumab IB.33
Revised Protocol No.: 06
Date: 05-Dec-2019
54
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
There is a potential for enhanced toxicity when combined with other immunotherapeutic agents. 
Combination nonclinical toxicology studies with BMS-813160 and nivolumab have not been 
conducted and are not required by the International Council on Harmonisation S9 Note for 
Guidance on Nonclinical Evaluation for Anticancer Pharmaceuticals. The safety of the 
combination will be carefully monitored in the planned clinical trial. 
The overall safety experience with nivolumab, as either monotherapy or in combination with other 
therapeutics, is based on experience in approximately 20,200 participants.33 Nivolumab 
monotherapy is approved in multiple countries, including the US, European Union (EU), and 
Japan. Nivolumab has been approved by the US FDA for the treatment of patients with 
unresectable or metastatic melanoma (as a single agent and in combination with ipilimumab), 
metastatic non-small cell lung cancer (NSCLC) after disease progression on or after platinum 
based chemotherapy, advanced renal cell carcinoma (RCC)
previously treated with 
anti-angiogenic therapy, recurrent or metastatic squamous cell carcinoma of the head and neck 
(SCCHN) with disease progression on or after a platinum-based therapy, classical Hodgkin 
lymphoma (cHL) that has relapsed or progressed, locally advanced or metastatic urothelial cancer 
after disease progression on or after platinum based chemotherapy, and other cancers.33
For nivolumab monotherapy, the safety profile is similar across tumor types. The only exception 
is pulmonary inflammation AEs, which may be numerically greater in participants with NSCLC. 
In NSCLC patients, it can be difficult to distinguish between nivolumab-related and 
nivolumab-unrelated causes of pulmonary symptoms and radiographic changes. Most AEs were 
low-grade (Grade 1 to 2) with relatively few related high-grade (Grade 3 to 4) AEs. There was no 
pattern in the incidence, severity, or causality of AEs with respect to nivolumab dose level. AEs 
have included pulmonary toxicity, renal toxicity (including acute renal failure), endocrine 
abnormalities, gastrointestinal (GI) toxicity, dermatologic toxicity (including rash), and 
hepatotoxicity. A pattern of immune-related AEs has been defined, for which management 
algorithms have been developed; these are provided in Appendix 6. Most high-grade events were 
manageable with the use of corticosteroids or hormone replacement therapy (endocrinopathies) as 
instructed in these algorithms. There is no relationship between the incidence, severity, or causality 
of AEs and the nivolumab dose level. 
There is a potential for enhanced toxicity when combined with other immunotherapeutic agents.
Nivolumab in combination with chemotherapy has been evaluated in multiple studies and many 
clinical trials are in progress. These trials so far have not shown any synergistic toxicity when 
immunotherapy was combined with chemotherapy. Additional details on the safety profile of 
nivolumab, including results from other clinical studies, are summarized in the nivolumab IB.33
3.2.2.1
Nonclinical Pharmacokinetics and Metabolism of Nivolumab
Please see the nivolumab IB33 for current data.
3.2.2.2
Clinical Pharmacokinetics of Nivolumab
Single-dose PK of nivolumab was evaluated in 39 participants with multiple tumor types in 
CA209001 in the dose range of 0.3 to 10 mg/kg. The median Tmax across dose levels ranged from 
Revised Protocol No.: 06
Date: 05-Dec-2019
55
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
1.6 to 3.1 hours with individual values ranging from 0.9 to 7 hours. The PK of nivolumab was 
linear in the range of 0.3 to 10 mg/kg with dose-proportional increase in Cmax and AUC(INF). 
Geometric mean clearance after a single intravenous (IV) dose ranged from 0.13 to 0.19 mL/h/kg, 
while mean volume of distribution of terminal phase (Vz) varied between 83 to 113 mL/kg across 
doses. The mean terminal T-HALF of nivolumab was 17 to 25 days, consistent with half-life of 
endogenous IgG4, indicating that the elimination mechanism of nivolumab may be similar to IgG4. 
Both elimination and distribution of nivolumab appeared to be independent of dose within the dose 
range studied.
The multiple dose PK of nivolumab given every 2 weeks (Q2W) in participants with multiple 
tumor types was determined from the CA209003 study as well as population PK (PPK) analyses 
using data from 909 participants across nivolumab studies. Multiple-dose PK of nivolumab 
following Q2W dosing was linear with dose-proportional increase in Cmax and area under the 
concentration-time curve in 1 dosing interval (AUC[TAU]) in the studied range of 0.1 to 10 mg/kg. 
The geometric mean of terminal T-HALF was 26.7 days and the typical CLR was 8.7 mL/h, which 
are consistent with those of full human immunoglobulin antibodies.
Nivolumab 480 mg every 4 weeks (Q4W) is currently under active clinical evaluation across 
multiple tumor types. Using a PPK model, nivolumab 480 mg Q4W is predicted to provide average 
steady-state concentrations (Cavgss) similar to nivolumab 3 mg/kg Q2W. Nivolumab 480 mg 
Q4W is predicted to provide greater (approximately 40%) maximum observed plasma 
concentration at steady state (Cmaxss) and lower (approximately 20%) trough steady-state 
concentrations (Cminss). Nivolumab has been shown to be safe and well tolerated up to doses of 
10 mg/kg Q2W and has not demonstrated a clear dose response or exposure-response safety 
relationship. Based on these safety findings, the predicted Cmaxss at 480 mg Q4W is not 
considered to put patients at increased risk for AEs. The approved doses of 3 mg/kg Q2W and 240 
mg Q2W have shown survival benefit across multiple tumor types compared to respective 
standards of care. Nivolumab exposure was not a predictor of survival in exposure-response 
efficacy analyses conducted for multiple tumor types. The Cminss values following nivolumab 
480 mg Q4W are predicted to be in the range of those on the flat part of the exposure-response 
efficacy curves and are not expected to impact efficacy. 
Clinical safety data across multiple studies and tumors (CA209511 [Part 2], CA209384, 
CA209017, CA209025, CA209057, and CA209066) support the modeling above. In addition, 
these studies suggest that there is no substantive difference in the safety profile of nivolumab 3 
mg/kg or 240 mg Q2W compared with 480 mg Q4W in terms of Grade 3/4 AEs, SAEs, AEs 
leading to discontinuation, and immune-mediated AEs. No new safety concerns were identified. 
These data show that the safety profiles of nivolumab 3 mg/kg Q2W, 240 mg Q2W, and 480 mg 
Q4W were similar, despite the increase in the Cmax with 480 mg Q4W. Nivolumab 480mg Q4W 
has been implemented in several trials across the nivolumab program. Nivolumab 480 mg Q4W 
infused over 30 minutes was FDA approved in March 2018 for most approved indications. The 
European Medicines Agency has also approved nivolumab 480 mg Q4W for the treatment of 
patients with melanoma (advanced or adjuvant treatment) and previously treated RCC.
Additional details are provided in the current version of the nivolumab IB.33
Revised Protocol No.: 06
Date: 05-Dec-2019
56
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
3.3
Benefit/Risk Assessment
Patients who have advanced solid tumors, including metastatic colorectal and pancreatic cancer,
have a poor prognosis and no curative options. There is no prior oncology experience with 
BMS-813160; therefore, clinical benefit has not been established in patients with advanced cancer. 
BMS-813160 has been evaluated in multiple clinical trials and established a well-tolerated safety 
profile. In CV202002 study, there were concentration-dependent increases in QRS and PR 
intervals and heart rate at 600 mg BID and 900 mg BID, without any ECG-related AEs or clinical 
sequalae.30 The increases in PR (mean < 16 msec at peak), QRS (mean < ~10 msec at peak), and 
heart rate (< ~10 bpm at peak) were not considered clinically significant. Concentration-response 
assessment showed no QTc prolongation. The most frequently reported AEs in CV202010 study 
were edema peripheral (6.8% of subjects), fatigue (5.7% of subjects), diarrhea (3.4% of subjects), 
back pain (3.4% of subjects), and headache (3.4% of subjects).34 This first-in-oncology assessment 
was based on preclinical and clinical data supporting clinical activity of either CCR2 or CCR5 
inhibition in combination with chemotherapy in pancreatic or CRC, respectively.
In combination with chemotherapy, BMS-813160 may potentiate chemotherapy-induced side 
effects in Arm A and B. However, clinical studies showed that the combination of either CCR2 or 
CCR5 inhibitors with chemotherapy in pancreatic cancer and CRC was tolerable and no 
unexpected toxicities were seen with the combinations.4,6 The toxicity profiles for the 
chemotherapy regimens in this study have been well characterized and oncologists are trained in 
managing these common toxicities with supportive care medications and dose interruptions or 
reductions. While these chemotherapy regimens have shown to improve survival of patients with 
metastatic colorectal and pancreatic cancer, more than half of CRC and three-fourths of pancreatic 
cancer patients have progression within 1 year of diagnosis on these regimens. Therefore, better 
treatment options are clearly needed. 
As of 30-Oct-2019, the safety profile of BMS-813160 is manageable with either 300-mg BID and 
600-mg QD dose. One DLT (Grade 3 rash) was observed with 300 mg BID BMS-813160 in 
combination with gemcitabine and nab-paclitaxel, and 1 DLT (pericardial effusion with 
pericarditis) was observed with 600 mg QD of BMS-813160 in combination with gemcitabine and 
nab-paclitaxel. Both of these participants have continued on the study treatment with 1 dose 
reduction for both BMS-813160 and chemotherapy and tolerated further treatment well. Overall, 
the AE profile appears to be similar to expected frequency in these cancers when combined with 
chemotherapy. The safety of the chemotherapy combinations with BMS-813160 will continue to 
be carefully monitored. Please refer to the IB for safety data of BMS-813160 in combination with 
chemotherapy in the study.27
In combination with nivolumab therapy, BMS-813160 may potentiate immune-mediated adverse 
reactions caused by nivolumab in Arm C. The combination with nivolumab was well tolerated in 
Part 1 of the study with no DLTs. The safety profile of nivolumab monotherapy is well defined 
and is based on experience with greater than 20,200 participants evaluated in clinical trials. The 
frequency and types of immune-mediated adverse reactions are similar across multiple types of 
tumors and are described in the Reference Safety Information in the current nivolumab IB.33
Revised Protocol No.: 06
Date: 05-Dec-2019
57
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Management algorithms for immune-induced AEs involving GI, renal, pulmonary, hepatic, 
endocrinopathy, skin, neurologic systems, and myocarditis are included in the protocol (see 
Appendix 6). The safety of the combination with nivolumab will be carefully monitored. 
The combination of Gem/nab-paclitaxel, nivolumab, and BMS-813160 has not been evaluated in 
previous clinical trials; however, based on well-tolerated safety profiles of respective double 
combinations and data from Part 2 Arm B Cohort 3b of the current study (CV202103) showing 
that no DLTs occurred in the 6 DLT-evaluable participants who received BMS-813160 + 
nivolumab + Gem/nab-paclitaxel, this combination is expected to be tolerable. Please see Section 
3.1.7 for further details. The combination was not started until at least 6 participants were treated 
with BMS-813160 300 mg BID in combination with Gem/nab-paclitaxel (Part 1, Arm B) and in 
combination with nivolumab (Part 1, Arm C) and all cleared the DLT period.
The mandated biopsies pose limited risk to the participant, and include discomfort, pain, and 
bleeding. Because of the need to understand the effect of BMS-813160 in tumors and the need for 
development of predictive biomarkers to select the patients most likely to benefit from 
BMS-813160, the limited risk of a research biopsy is considered appropriate in an early phase 
clinical trial research setting. Biopsies will be performed only if deemed an acceptable clinical risk 
as judged by the investigator.
Continuous safety assessments will be utilized by the Investigators and Bristol-Myers Squibb
(BMS) to determine whether dose modification, additional safety measures, or termination of the 
study is required at any time. In addition, AEs and SAEs will be reviewed on an ongoing basis by 
the BMS Medical Monitor and Global Pharmacovigilance and Epidemiology representatives to 
monitor for any safety signals or trends. As BMS-813160 is an experimental agent, it is possible 
that unforeseen, unknown, or unanticipated reactions may occur. The protocol was developed 
carefully balancing risks and benefits of treatment of a novel treatment in this patient population 
with an unmet medical need.
3.3.1
Safety Monitoring on Study Treatment
Frequent safety assessments will be carried out by the Sponsor/BMS Medical Monitor (or 
designee) and investigators throughout the study to determine whether dose modification, 
additional safety measures, or termination of the study treatment combination arm is required at 
any time. In addition, BMS has developed a multi-layered process to ensure safety monitoring 
through close collaboration of study site investigators, the BMS study team, and the BMS Global 
Pharmacovigilance and Epidemiology (GPVE) led Safety Management Team (SMT), which is 
composed, at a minimum, of the GPVE medical safety assessment physician (Chairman of the 
SMT) and GPVE single case review physician, the study Medical Monitor, the study 
biostatistician, and epidemiologist; all of whom, analyze the data in an unblinded fashion. 
Furthermore, the SMT routinely monitors for actual or potential issues related to participant safety 
that could result in a change in the medical risk-benefit balance associated with the use of study 
treatment(s). This collaborative process constitutes the safety monitoring plan for the study. To 
support safety oversight, BMS has established ongoing processes for collection, review, analysis, 
and submission of individual AE reports and their aggregate analyses. Because this is an open-label 
Revised Protocol No.: 06
Date: 05-Dec-2019
58
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
study, GPVE, the BMS Medical Monitor, and the investigators will have access to all data 
necessary for safety evaluation. Treatment of AEs will follow institutional guidelines and 
recommended management algorithms, as listed in the IBs and prescribing information, as 
applicable, for each combination agent and contemporaneous control comparator, and provided as 
appendices to this protocol. Specific algorithms for the management of immune-related AEs are 
provided in Appendix 6 and are applicable to immune-related AEs for all immuno-oncology study 
treatment combinations.
Revised Protocol No.: 06
Date: 05-Dec-2019
59
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
4
OBJECTIVES AND ENDPOINTS
The objectives and endpoints for the primary, secondary, and exploratory analyses of this study 
are shown in Table 4-1 (Part 1) and Table 4-2 (Part 2).
Table 4-1:
Objectives and Endpoints (Part 1)
Objectives
Endpoints
Primary
1) To assess the safety and tolerability of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel (Arm B), or nivolumab (Arm C) in 
participants with advanced CRC or pancreatic cancer
2) To assess the pharmacodynamic effects of BMS-813160 in 
tumor samples
1a) Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs leading 
to discontinuation, and death; Incidence of 
laboratory abnormalities
1b) Additional safety endpoints: summary 
measures of vital signs or ECGs
2)
Decrease in Treg or TAM in tumor samples
Secondary
1) To assess the preliminary efficacy of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel (Arm B), or nivolumab (Arm C) in 
participants with advanced CRC or pancreatic cancer
2) To characterize the PK of BMS-813160 and its metabolite 
(BMS-939429) when administered alone, and in combination 
with either Gem + nab-paclitaxel, FOLFIRI or nivolumab
3) To characterize the immunogenicity of nivolumab when 
administered in combination with BMS-813160
1)
ORR, median DOR, and PFS rate at 24 
weeks
2a) PK parameters, such as Cmax, Tmax, 
Ctrough, C24, AUC(0-8), AUC(0-24), 
CLT/F, AI, CLR, %UR, MR_Cmax, and 
MR_AUC(0-24), if data permit
2b) Cmax and Ctrough concentrations of 
BMS-813160 during combination therapy
3)
Frequency of positive ADA to nivolumab 
during combination therapy
Exploratory
1) To characterize the PK of nivolumab when administered in 
combination with BMS-813160
2) To assess the potential effect of BMS-813160 monotherapy 
on the CLR of NMN an endogenous biomarker for multidrug 
and toxin extrusion transporters (MATE1 and MATE2-K) 
3) To assess the potential effect of BMS-813160 monotherapy 
on levels of NMN, an endogenous marker for renal 
transporters
4) To assess the pharmacodynamic effects of BMS-813160 in 
peripheral blood
5) To assess OS
1)
Concentrations at end of infusion and 
Ctrough for nivolumab during combination 
therapy
2,3)Change of NMN in plasma and urine and 
CL change of creatinine levels in plasma 
and urine and CLR
4)
Change of MCP-1 and CCR2 positive
monocyte count in peripheral blood
5)
OS rate at 1 year and 2 years
Abbreviations: %UR = percent urinary recovery over dosing interval; ADA = anti-drug antibody; AEs = adverse 
events; AI = accumulation index; AUC(0-8) = area under the concentration-time curve from time 0 to 8 hours post 
dose; AUC(0-24) = area under the concentration-time curve from time 0 to 24 hours post dose; C24 = observed plasma 
concentration at 24 hours post dose (for QD dosing only); CCR2 = cysteine-cysteine chemokine receptor 2; CL = 
clearance; CLR = renal clearance; CLT/F = apparent total body clearance; Cmax = maximum observed plasma 
concentration; CRC = colorectal cancer; Ctrough = trough observed plasma concentration; DLT = dose limiting 
toxicity; DOR = duration of response; ECGs = electrocardiograms; FOLFIRI = FOL (folinic acid [leucovorin]) F 
(fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; MATE = multidrug and toxin 
extrusion protein; MCP-1 = monocyte chemotactic protein-1; MR_AUC(0-24) = ratio of metabolite AUC(0-24) to 
parent AUC(0-24), corrected for molecular weight; MR_Cmax = ratio of metabolite Cmax to parent Cmax, corrected 
for molecular weight; NMN = N-methylnicotinamide; ORR = objective response rate; OS = overall survival; PFS = 
progression-free survival; PK = pharmacokinetic(s); SAEs = serious adverse events; TAM = tumor-associated 
macrophages; Tmax = time of maximum observed plasma concentration; Treg = regulatory T cells.
Revised Protocol No.: 06
Date: 05-Dec-2019
60
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 4-2:
Objectives and Endpoints (Part 2)
Objectives
Endpoints
Primary
1) To assess the preliminary efficacy of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel or nivolumab + Gem + nab-paclitaxel
(Arm B), or nivolumab (Arm C), and as monotherapy 
(Arm D) in participants with advanced CRC or pancreatic 
cancer
1)
ORR as assessed by investigator using 
RECIST v1.1, median DOR, and PFS rate at 
24 weeks
Secondary
1) To assess the safety and tolerability of BMS-813160 in 
combination with either FOLFIRI (Arm A), Gem + 
nab-paclitaxel or nivolumab + Gem + nab-paclitaxel
(Arm B), or nivolumab (Arm C), and as monotherapy 
(Arm D) in participants with advanced CRC or pancreatic 
cancer
2) To assess the pharmacodynamic effects of BMS-813160 in 
tumor samples
1a) Incidence of AEs, SAEs, AEs leading to 
discontinuation, and death; incidence of 
laboratory abnormalities.
1b) Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria in Cohort 3b
1c) Additional safety endpoints: summary 
measures of vital signs or ECG
2)
Decrease in Treg & TAM in tumor samples
Exploratory
1) To assess the PK of BMS-813160 when administered as 
monotherapy and with different chemotherapy or nivolumab 
combination regimens
2) To characterize the immunogenicity of nivolumab when 
administered in combination with BMS-813160 or 
BMS-813160 plus chemotherapies
3) To assess the pharmacodynamic effects of BMS-813160 in 
peripheral blood
4) To assess the PK of irinotecan and nab-paclitaxel in a subset 
of participants when combined with BMS-813160
5) To assess OS
1a) Cmax and Ctrough concentrations of 
BMS-813160 during monotherapy and 
combination therapy
1b) Concentrations at end of infusion and 
Ctrough for nivolumab during combination 
therapy
2)
Frequency of positive ADA to nivolumab 
during combination therapy
3)
Change of MCP-1 and CCR2 positive 
monocyte count in peripheral blood
4)
Cmax, Tmax, AUC(0-24), Ctrough of 
irinotecan, SN-38, and nab-paclitaxel
5)
OS rate at 1 year and 2 years
Abbreviations: ADA = anti-drug antibody; AEs = adverse events; AUC(0-24) = area under the concentration-time 
curve from time 0 to 24 hours post dose; CCR2= cysteine-cysteine chemokine receptor 2; Cmax = maximum observed 
plasma concentration; CRC = colorectal cancer; Ctrough = trough observed plasma concentration; DLT = dose-
limiting toxicity; ECGs = electrocardiograms; FOLFIRI = FOL (folinic acid [leucovorin]) F (fluorouracil [5-
fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; MCP-1 = monocyte chemotactic protein-1; ORR 
= objective response rate; OS = overall survival; PK = pharmacokinetics; RECIST = Response Evaluation Criteria in 
Solid Tumors; SAEs = serious adverse events; TAM = tumor-associated macrophages; Tmax = time of maximum 
observed plasma concentration; Treg = regulatory T cells.
Revised Protocol No.: 06
Date: 05-Dec-2019
61
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
5
STUDY DESIGN
5.1
Overall Design
This is a Phase 1b/2, open-label, 2-part, multicenter trial to assess the safety, tolerability, PK, 
pharmacodynamics, and preliminary efficacy of BMS-813160 alone or in combination with either 
FOLFIRI, Gem/nab-paclitaxel, Gem/nab-paclitaxel and nivolumab, or nivolumab in participants 
with advanced CRC or pancreatic cancer. 
The study is divided into 3 periods: Screening, Treatment, and Follow-up (Safety and Survival 
Phases). The study design scheme is presented in Figure 5.1-1 (Part 1) and Figure 5.1-2 (Part 2).
Revised Protocol No.: 06
Date: 05-Dec-2019
62
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Figure 5.1-1:
Study Design Schematic (Part 1)
Note: FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours [leucovorin may be given concurrently with irinotecan]; 5-FU 
400 mg/m2 bolus followed by 2400 mg/m2 over 46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle.
Note: The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an intravenous infusion over 30 to 40 minutes on Days 1, 8, and 15 
of each 28-day cycle. Administer gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Note: Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks.
Abbreviations: 1L = first-line; 2L = second-line; 3L = third-line; 5-FU = 5-fluorouracil; BID = twice a day; CRC = colorectal cancer; FOLFIRI = FOL (folinic acid 
[leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); m2 = square meter; MSS = microsatellite stable; QD = once daily.
a Bevacizumab, cetuximab, or panitumumab can be added to 1L FOLFIRI if appropriate.
b Participants will continue on the combination until disease progression, intolerance to treatment, meeting discontinuation criteria, or withdrawal of consent.
c Safety follow-up: 30 days for Arms A and B and 100 days for Arm C. Survival follow up to begin after completion of safety follow-up every 12 weeks 
(± 2 weeks) until 2 years after last dose of study treatment.
Revised Protocol No.: 06
Date: 05-Dec-2019
63
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Figure 5.1-2:
Study Design Schematic (Part 2) - Combination Therapy Expansion
Note 1: FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours [leucovorin may be given concurrently with irinotecan]; 5-FU 
400 mg/m2 bolus followed by 2400 mg/m2 over 46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle.
Note 2: The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an intravenous infusion over 30 to 40 minutes on Days 1, 8, and 
15 of each 28-day cycle. Administer gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Note 3: Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks. In Cohort 3b, administer nivolumab followed by chemotherapy 
30 minutes later.
Abbreviations: 1L = first-line; 2L = second-line; 3L =third-line; 5-FU = 5-fluorouracil; BID = twice a day; FOLFIRI = FOL (folinic acid [leucovorin]) F 
(fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]); Gem = gemcitabine; MSS = microsatellite stable; Nivo = nivolumab; ORR = objective response 
rate; PD = progressive disease progression; QD = once daily
Revised Protocol No.: 06
Date: 05-Dec-2019
64
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
a Participants will continue on the combination until disease progression (PD), intolerance to treatment, meeting discontinuation criteria, or withdrawal of consent.
b Lower dose: BMS-813160 150 mg QD (see Section 3.1.6 for further details).
c Participants in Cohort 1c will be allowed to cross over to Cohort 5 at the time of PD if it’s felt to be in their best interest by their treating physician and participants 
meet all eligibility criteria to enroll in Arm C. Participants will have to meet all eligibility criteria to re-enter the study, undergo baseline assessment (Table 2-2) 
and need a 28-day washout period prior to first dose of study treatment in the new arm.
d Safety follow-up: 30 days for Arms A, B (Cohorts 3a and 3c), and D; 100 days for Arm C and Cohort 3b (see Table 2-7 for further details). Survival follow up 
to begin after completion of safety follow-up every 12 weeks (± 2 weeks) until 2 years after last dose of study treatment.
e The Gem/nab-paclitaxel in combination with nivolumab and BMS-813160 cohort had a safety lead-in of approximately 6 participants who were treated with 
BMS-813160 300 mg BID and monitored for 4 weeks before additional participants are added to the cohort. In addition a staggered dosing (sentinel participant) 
approach was used for the first 3 participants. The first participant to be dosed was observed for 5 days, before additional participants (ie, participant 2 and 3) 
received study treatments.
f Arm D (BMS-813160 monotherapy) will only open if participants in Arm C show an ORR of approximately 15% or durable responses are seen with the 
combination of nivolumab and BMS-813160.
g Cohort 4 was closed per Revised Protocol 06. Participants in Cohort 3c can no longer crossover to Cohort 4 per Revised Protocol 06.
h Cohort 7 will not open for enrollment due to Cohort 4 being closed due to futility per Revised Protocol 06.
Revised Protocol No.: 06
Date: 05-Dec-2019
65
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
5.1.1
Screening Period
The screening period will last for up to 28 days. The screening period begins by establishing the 
participant’s initial eligibility upon signing of the informed consent form (ICF). The screening 
assessments are shown in Table 2-1. If a participant surpasses the 28-day window during the 
screening period due to a study-related procedure (eg, scheduling of a tumor biopsy or waiting 
time for a study-related laboratory value), the participant must be re-consented but does not need 
to be assigned a new participant identification (PID) number. In this situation, the least amount of 
repeat procedures from the initial screening to qualify the participant, while maintaining safety 
and eligibility under the discretion of the BMS Medical Monitor and investigator, may be done to 
reduce any undue burden of procedure in this participant population. Participants will be treated 
in 1 of 3 arms as described in the following sections. Allocation will be based on availability of 
slots in each of the 3 arms and participants meeting cohort-specific eligibility criteria.
5.1.2
Treatment Period (Part 1)
Treatment period (Part 1) will have a 2-week monotherapy lead-in with BMS-813160 prior to 
combination with either FOLFIRI, Gem/nab-paclitaxel, or nivolumab. All 3 arms will enroll 
participants in parallel. Participants will be assigned to the BMS-813160 300 mg BID or 600 mg 
QD cohort in each arm of the study. Participant assignment is detailed in Section 7.2. 
Approximately 6 evaluable participants will be treated at each BMS-813160 dose (ie, 300 mg BID
or 600 mg QD) for a total of approximately 12 participants per arm. Up to 6 additional participants 
will be added to evaluate BMS-813160 dose of 150 mg QD and 300 mg QD to better characterize 
PK and PD of lower doses of BMS-813160 in combination with nivolumab (see Section 3.1.6 for 
details on the rationale). Approximately 6 additional participants may be added to a dose cohort to 
better characterize the safety, PK, or pharmacodynamic profile and inform Part 2 dose selection of 
BMS-813160 if needed after discussion with the Sponsor and investigators. 
The BMS-813160 monotherapy lead-in allows assessment of initial tolerability in cancer 
participants, facilitating the characterization of the added or synergistic toxicity of the subsequent 
combination regimens, and enables a biopsy at 2 weeks to characterize PD effects of BMS-813160. 
After 2 weeks of BMS-813160 monotherapy, participants will start the combination phase with 
either FOLFIRI, Gem/nab-paclitaxel, or nivolumab along with continued treatment with 
BMS-813160 after a mandatory biopsy (± 3 days) is performed. Monotherapy should continue if 
biopsy is collected beyond 2 weeks and combination with chemotherapy or nivolumab should only 
begin after the biopsy is performed. Participants will continue on combination until disease 
progression, intolerance, meeting criteria for treatment discontinuation (Section 8), or withdrawal 
of consent.
5.1.3
Treatment Period (Part 2)
Treatment period (Part 2) will explore the preliminary signals of efficacy of BMS-813160 with 
various combinations as described below. The recommended Phase 2 dose of BMS-813160 in 
Part 2 was chosen based on safety, PK, and pharmacodynamic data available from Part 1 of the 
study. Based on these considerations, BMS-813160 300 mg BID dosing regimen was selected for 
primary investigation in this study. A regimen of BMS-813160 150 mg QD in combination with 
Revised Protocol No.: 06
Date: 05-Dec-2019
66
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
FOLFIRI will be also evaluated in Arm A. Participants in Part 2 will be treated with BMS-813160
alone or in combination with either FOLFIRI, Gem/nab-paclitaxel, Gem/nab-paclitaxel and 
nivolumab, or nivolumab without a BMS-813160 monotherapy lead-in. 
There will be 4 study arms (Arms A, B, C, and D) containing a total of 10 cohorts. Arm D (BMS-
813160 monotherapy) will only open if participants in Arm C show an ORR of approximately 
15% or durable responses are seen with the combination of nivolumab and BMS-813160 where 
durable response is defined as a continuous response (objective CR or PR) beginning within 
12 months of treatment and lasting ≥6 months. Please see Section 3.1.8 for further details on Arm 
D.
Participants in Arm A will include 2L CRC and will be randomized to 1 of 3 arms. FOLFIRI in 
combination with BMS-813160 300 mg BID or 150 mg QD, or FOLFIRI alone. Please see Section 
3.1.6 for rationale for BMS-813160 150 mg QD dose.
Participants in Arm B will include 1L pancreatic cancer and will be randomized to 1 of 3 arms:
Gem/nab-paclitaxel in combination with BMS-813160 300 mg BID, Gem/nab-paclitaxel in 
combination with BMS-813160 300 mg BID and nivolumab 480 mg Q4W, or Gem/nab-paclitaxel 
alone. The Gem/nab-paclitaxel in combination with nivolumab and BMS-813160 300 mg BID 
(Cohort 3b) will have a safety lead-in of approximately 6 participants who will be treated and 
monitored for 4 weeks before additional participants are added to the cohort. In addition a 
staggered dosing (sentinel participant) approach will be used for the first 3 participants. After the 
first 3 participants are treated, at a 5-day interval, with the combination, the subsequent 
3 participants may be enrolled competitively. Approximately 6 participants will be monitored for 
4 weeks before additional participants may be treated in the same cohort. After approximately 
6 evaluable participants are randomized in Cohort 3b, it will be paused for enrollment for safety
evaluation while Cohort 3a and Cohort 3c will continue to randomize participants. These 
participants will be monitored closely for DLTs as per DLT criteria described in 7.4.1. If greater 
than 33% (2 or more) meet DLT criteria, then 1 dose level lower will be explored.
Participants in Arm C will include 2L pancreatic cancer (Cohort 4 closed per Revised Protocol 
06) and 2/3L MSS CRC and will be treated with BMS-813160 300 mg BID in combination with 
nivolumab.
Participants in Arm D will include 2L pancreatic cancer and 2/3L MSS CRC and will be treated 
with BMS-813160 300 mg BID alone.
A biopsy will be obtained 4 weeks (± 3 days) after the first dose in Part 2 for correlative studies. 
Participants on bevacizumab or its biosimilar in Arm A should be off bevacizumab or its biosimilar 
for at least 14 days or according to institutional guidelines to prevent any bleeding or delay in 
wound healing.
Participants will continue on combination until disease progression, intolerance, meeting criteria 
for treatment discontinuation (Section 8), or withdrawal of consent.
Revised Protocol No.: 06
Date: 05-Dec-2019
67
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
5.1.4
Treatment Period (Parts 1 and 2)
Blood, urine, and tumor biopsy samples and ECGs will be collected and participants will receive 
study treatments as per the schedule of activities (Table 2-3, Table 2-4, Table 2-5, and Table 2-6). 
Participants will have baseline imaging within approximately 28 days of start of the study and then 
every 8 weeks after starting combination treatment for reassessment. Tumor progression or 
response endpoints will be assessed using RECIST v1.1 for solid tumors. Participants will continue 
on treatment until disease progression, clinical deterioration, toxicity, meeting criteria for 
discontinuation of study treatment (Section 8), or withdrawal of consent. Participants who go off 
treatment will be followed for safety assessments and survival status as defined in Table 2-7.
Treatment beyond disease progression (Arm C only) may be allowed in select participants with 
initial RECIST v1.1 defined progressive disease (PD) after discussion and agreement with the 
BMS Medical Monitor that the benefit/risk assessment favors continued administration of study 
treatment (eg, participants are continuing to experience clinical benefit as assessed by the 
investigator, tolerating treatment, and meeting other criteria specified in Section 7.4.8).
Participants in Cohort 1c will be allowed to cross over to Cohorts 5 at the time of disease 
progression if it’s felt to be in their best interest by their treating physician and participants meet 
all eligibility criteria to enroll in Arm C. Participants in Cohort 3c will not be allowed to cross over 
to Cohort 4 at the time of disease progression since Cohort 4 was closed per Revised Protocol 06. 
Participants will have to meet all eligibility criteria to re-enter the study, undergo baseline 
assessment (Table 2-2) and need a 28-day washout period prior to the first dose of study treatment 
in the new arm. If Cohort 5 is closed due to safety or futility, participants will not be allowed to 
cross over from Cohort 1c. 
Participants with a response of SD, PR, or CR at the end of a given cycle will continue to the next 
treatment cycle. Participants will generally be allowed to continue study treatment until the first 
occurrence of either 1) PD, 2) clinical deterioration suggesting that no further benefit from 
treatment is likely, 3) intolerability to therapy, 4) the participant meets criteria for discontinuation 
of study treatment as outlined in Section 8, or 5) withdrawal of consent.
Physical examinations, vital sign measurements, 12-lead ECG, and clinical laboratory evaluations 
will be performed at selected times throughout the dosing interval. In the event multiple procedures 
are required at a single time point, the following is a list of procedures from highest priority to 
low: PK sampling, ECG and vital signs, and laboratory tests. Participants will be closely monitored 
for AEs throughout the study. Blood and urine samples will be collected at baseline and after study 
treatment administration for PK and multidrug and toxin extrusion (MATE)-renal transporter 
biomarker analyses according to the schedules outlined in Section 9.5. 
5.1.5
Follow-up Period (Parts 1 and 2)
During Follow-up, participants will follow the Follow-up Procedural Outline in Section 2 (Table 
2-7).
Revised Protocol No.: 06
Date: 05-Dec-2019
68
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
5.1.5.1
Safety Follow-up
For all participants, the end of treatment (EOT) visit will be the most recent on-treatment visit 
(with all available safety and response data) and does not need to be repeated, and will be 
considered the start of the Week 1 Clinical/Safety Follow-up visit. 
Participants must be followed for at least 30 days (± 7 days) in all cohorts in Arms A, Cohorts 3a 
and 3c in Arm B, and Cohorts 7 and 8 in Arm D after the last dose of study treatment to monitor 
for AEs. Follow-up visits in Cohort 3b in Arm B and Cohorts 4 (closed per Revised Protocol 06) 
and 5 in Arm C should occur at Days 30, 60, and 100 (± 7 days) after the last dose of study 
treatment to monitor for AEs to account for the long half-life of nivolumab. All participants, except 
those participants who withdraw consent for study participation, will be required to complete 
Clinical/Safety Follow-up visits regardless of whether they start a new anti-cancer therapy. 
If participants cannot be seen in clinic for any of the follow up visits, at least a telephone follow 
up is recommended.
5.1.5.2
Survival Follow-up
After completion of the Safety Follow-up Phase, all participants will enter the Survival Follow-up 
Phase. Participants will be followed up (by telephone or clinic visit) every 12 weeks (Q12W)
[± 2 weeks], from the last dose of study treatment for 2 years or until death, loss to follow-up, 
withdrawal of consent, or conclusion of the study, whichever comes first. 
The duration of this phase is up to 2 years following the last dose of study treatment, although a 
longer follow-up phase could be considered in selected cases if an efficacy signal is apparent.
Data from imaging assessments for participants who have ongoing clinical benefit may continue 
to be collected while participants complete the survival phase of the study.
5.1.6
Data Monitoring Committee and Other External Committees
BMS has elected not to use a Data Monitoring Committee for this study. In addition to the 
comprehensive safety monitoring plan outlined below, the following key points were considered 
for this decision:
•
This is an open label study.
•
The eligibility criteria exclude participants with disease characteristics that could predispose
to higher risk of morbidity, eg, history of interstitial lung disease, recent history of coronary
thrombosis, etc. 
•
Exclusion of participants with known autoimmunity also applies as they could be at risk for 
exacerbation of their condition by the administration of therapies that relieve immune 
suppression such as nivolumab.
•
Participants will be observed frequently for clinical evaluation and blood counts during dose 
escalation.
•
Well-defined discontinuation criteria are established in the protocol for individual participants 
for both safety and treatment futility with clear criteria for treatment discontinuation, dose 
delay, and toxicity management.
Revised Protocol No.: 06
Date: 05-Dec-2019
69
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
BMS has in place a multi-layered process for ensuring participant safety through close 
collaboration of study site investigators, the BMS study team, and the BMS GPVE-led SMT. This 
collaborative process constitutes the Data Safety Monitoring Plan for the study as detailed below:
Study safety is evaluated continuously by representatives of BMS GPVE, who operate 
independently from the clinical team and monitor safety across all BMS protocols. AEs are 
monitored continuously by GPVE. Signal detection is performed at least monthly and ad hoc 
throughout the study by the SMT composed, at a minimum, of the GPVE medical safety 
assessment physician (Chairman of the SMT) and GPVE single case review physician, the study 
Medical Monitor(s), the study biostatistician, and epidemiologist. The SMT monitors actual or 
potential issues related to participant safety that could result in a significant change in the medical 
risk-benefit balance associated with the use of study treatments. Furthermore, investigators will be 
kept updated of important safety information, such as DLTs, during teleconferences between 
investigators and the BMS clinical team that will be held approximately every 2 weeks during Part 
1 dose selection and at least monthly during Part 2 cohort expansion. If appropriate, select safety 
issues may be escalated to a senior level, multidisciplinary, BMS wide Medical Review Group for 
further evaluation and action.
To support safety oversight, BMS has established ongoing processes for collection, review, 
analysis, and submission of individual AE reports and their aggregate analyses. Because this is an 
open label study, the BMS Medical Monitor and the investigators will have access to all data 
necessary for safety evaluation.
All participants in this study represent individuals with high unmet medical need as the prognosis 
for advanced/metastatic solid tumors is generally very poor.
5.2
Number of Participants
Approximately 54 evaluable participants (6 to 9 participants per dose per treatment arm) may be 
treated in Part 1 (monotherapy lead-in/combination safety). If additional participants are enrolled 
(as indicated in Section 5.1.2), approximately 48 additional participants could be enrolled in Part 1 
(6 participants per dose per treatment arm or per lower doses [150 mg QD and 300 mg QD] of 
BMS-813160 in combination with nivolumab). Approximately 308 evaluable participants may be 
treated in Part 2, Cohorts 1a to 8 (efficacy expansion) [approximately 35 evaluable participants 
per tumor indication per treatment in Arms A and B and approximately 31 evaluable participants 
per tumor indication per treatment in Arm C, details are given in Section 10.1]. For each of the 
pancreatic and CRC MSS cohorts, approximately 18 additional evaluable participants will be 
treated in a treatment Arm D (BMS-813160 monotherapy) [opens if ORR of approximately 15% 
or durable responses are seen in Arm C]. The number of participants will be continuously 
monitored such that the number of evaluable participants in Part 2 will not exceed 40 in any cohort. 
If the study is expanded further to add more participants, a protocol amendment will be submitted 
justifying the sample size (see Section 10 for further details).
5.3
End of Study Definition
The start of the trial is defined as the first visit for first participant screened. End of trial is defined 
as the last visit or scheduled procedure shown in the schedule of activities (see Section 2) for the 
Revised Protocol No.: 06
Date: 05-Dec-2019
70
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
last participant. Study completion is defined as the final date on which data for the primary 
endpoint is expected to be collected.
5.4
Scientific Rationale for Study Design
5.4.1
Rationale for Monotherapy Lead-in Part 1
This first-in-oncology study has been designed to balance the need to evaluate safety of 
BMS-813160 and preliminary signal of efficacy of BMS-813160 in combination with either 
chemotherapy or nivolumab in patients with advanced CRC or pancreatic cancer. The 2-week 
monotherapy lead-in will determine safety, PK, and pharmacodynamic effects of BMS-813160 
alone before it is combined with other agents. 
5.4.2
Rationale for Testing 2 Different Doses of BMS-813160 in Part 1
BMS-813160 is well tolerated in both QD and BID dosing regimens in prior studies. The BID 
dosing appears to engage target receptor for the whole 24 hours. Once a day dosing is preferable 
in oncology patients due to patient convenience and better compliance, and based on the T-HALF 
may also allow target engagement for the full 24 hours. In addition there are differences in Cmax 
and potential differences in DDI with once a day and twice a day dosing. Participants receiving 
BMS-813160 in combination with either chemotherapy or nivolumab will be closely monitored 
for any side effects. Exploring 2 different dosing regimens in Part 1 will enable BMS to move 
forward to Part 2 with a dose and schedule of BMS-813160 based on data generated from Part 1.
5.4.3
Rationale for 2-Stage Design in Cohorts in Arm C
Participants in these cohorts are receiving study treatments with no proven activity in these specific 
patient populations. Nivolumab and BMS-813160 are being tested in pancreatic cancer (Cohort 4
closed per Revised Protocol 06) and MSS CRC (Cohort 5) where nivolumab or BMS-813160 has 
not shown any significant clinical activity. A 2-stage design will provide a guide for futility and 
preliminary antitumor activity, and avoid exposing a large number of participants to a regimen 
which may be inactive (see Section 10.1).
5.4.3.1
Rationale for Closing Cohort 4
Following a predetermined analysis at Stage 1, Part 2 Cohort 4 (BMS 813160 in combination with 
nivolumab in 2L pancreatic cancer) was closed to enrollment due to futility and all participants 
have completed study treatment. 
Revised Protocol 06 implements the following:
•
Participant enrollment in Part 2 Cohort 4 is closed due to futility. Closure of this cohort was
not due to safety concerns.
•
Participants in Part 2 Cohort 3c who progress on 1L chemotherapy can no longer cross over to 
Cohort 4 since it was closed due to lack of clinical response.
•
Participants in Cohort 4 who have received treatment with BMS-813160 + nivolumab will 
continue to be followed through the study follow-up phases (Table 2-7) or until study 
discontinuation criteria have been met, whichever occurs first.
Revised Protocol No.: 06
Date: 05-Dec-2019
71
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Cohort 7 (BMS-813160 monotherapy; 2L pancreatic cancer) will not open for enrollment 
because opening of this cohort was dependent on an ORR of approximately 15% or durable 
responses observed in Cohort 4, which was closed due to lack of clinical response.
5.4.4
Rationale for Control Arms
Evaluating efficacy of a combination in a single arm study can be difficult due to many 
uncertainties, particularly if part of the combination has known anti-tumor activity. In addition, 
historical control may not be fully representative of the patient population in this study. 
The control arms for Arm A (FOLFIRI) and Arm B (Gem/nab-paclitaxel) are added to better 
evaluate safety and efficacy of BMS-813160 combined with either FOLFIRI or 
Gem/nab-paclitaxel ± nivolumab, respectively. These control arms provide a reference for safety 
and efficacy of FOLFIRI and Gem/nab-paclitaxel alone and help interpret the data in terms of the 
comparison between a treatment arm and control arm. Stratification by tumor sidedness in Arm A 
and by prior neoadjuvant/adjuvant therapy or not in Arm B was planned, but in error was omitted 
from the IRT system. As the cohorts were largely enrolled when the error was discovered, 
stratification was removed from the protocol with Revised Protocol 06. All of the planned 
stratification factors have been collected and can be analyzed retrospectively; thus, the lack of 
stratification is not expected to affect the scientific validity of the study. Microsatellite instability 
(MSI) status will be collected on all patients if available locally, and BMS plans to perform MSI 
testing retrospectively on all patients. BMS will conduct exploratory analyses to evaluate MSI 
status as a prognostic biomarker in the different treatment cohorts.
5.4.5
Rationale for MATE1-renal Biomarker Sample Collection
BMS-813160 is an inhibitor of MATE1, with an IC50 value of 4.6 μM. In contrast, it showed low 
potential to inhibit MATE2-K (the IC50 value was > 300 μM, the highest concentration tested). 
Based on the human steady state Cmax values at doses within the anticipated clinical range (300 to 
600 mg BID, Study CV20200230), 925.1 to 2547.8 ng/mL (~1.9 to 5.3 μM), BMS-813160 may 
reduce the renal CLR and increase the renal accumulation of drugs that are substrates of MATE1, 
although overlap in substrate specificity between the 2 transporters may mitigate this effect. The 
CLR of creatinine and N-methyl nicotinamide (NMN), endogenous substrates of MATE1 and 
MATE2-K transporters and biomarkers of renal transporter function, will be determined before 
and during BMS-813160 treatment to provide insight to the potential effect of BMS-813160 on 
renal transport function of MATE substrates such as cisplatin and oxaliplatin.
5.4.6
Rationale for Using BMS-813160 Tablet
BMS-813160 film-coated tablets, 75 mg and 300 mg for oral administration have been developed 
for clinical studies. The change from capsules to film-coated tablets involves making minor 
compositional changes to the current capsule formulation. The process to produce granules for 
compression into tablets is largely unchanged except with the introduction of fluid bed drying vs 
tray drying of material used in capsules. The biorelevant dissolution profiles in simulated intestinal 
fluid of capsules and tablets at the 300 mg dose are similar (300 mg film coated tablet vs two 150 
mg capsules). In addition, BMS-813160 drug substance is highly soluble over the pH range of 
Revised Protocol No.: 06
Date: 05-Dec-2019
72
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
1 - 6.8.27 The relative bioavailability of BMS-813160 administered as a single 300 mg (6 × 50 mg) 
oral dose in capsules was very similar to that from a 300 mg oral dose in solution, and there was 
no meaningful formulation effect in healthy subjects in Study CV202005.27 Based on the 
biorelevant dissolution similarity, minor change in composition, and given that BMS-813160 is a 
highly soluble compound, it is expected that there will be no impact on exposure due to the change 
from capsules to tablets.
5.5
Rationale for Dose
5.5.1
Rationale for Dose Selection of BMS-813160
Based on safety, PK, and pharmacodynamic findings from SAD and multiple ascending dose 
studies, the BMS-813160 300 mg BID dosing regimen was selected for investigation in Part 1 of 
this study. BMS-813160 trough plasma concentrations in healthy participants who received a 
300 mg BID dose for 14 days exceeded the 2x IC90 concentrations for both CCR2 binding and 
MIP-1β stimulated CCR5 phosphorylation. Sustained inhibition of CCR2 and CCR5 on Day 14 
was observed at doses ≥300 mg BID, indicating the achievement of target engagement. 
Additionally, the BMS-813160 300 mg BID dosing regimen was tolerable in healthy participants
and participants with DKD.
As the half-life of BMS-813160 (~12 to 16 hours) may have supported the use of a QD regimen, 
the 600 mg QD regimen was also investigated in Part 1 of this study. The trough concentration of 
the 600 mg QD regimen at steady state exceeded the IC90 concentrations for both CCR2 binding
and MIP-1β stimulated CCR5 phosphorylation. At 600 mg QD, CCR2 inhibition was saturated 
over the 24 hour dosing interval. CCR5 inhibition also appeared to reach a maximum, although 
the effect was not sustained over the 24 hour interval. Based on the ECG data observed in healthy 
participants, the 600 mg QD regimen is not expected to produce PR interval prolongation in 
patients.
The selection of the Part 2 dose for BMS-813160 in CV202103 is primarily based on available 
data from Part 1 of CV202103. At 300 mg BID, preliminary PK data suggested similar average 
plasma levels of BMS-813160 in cancer patients relative to that in healthy subjects. Based on the 
higher Cmax at steady state with the 600 mg QD dose and the lack of apparent difference in 
pharmacodynamics or safety between the 300 mg BID and 600 mg QD dose, 300 mg BID has 
been chosen as the primary dose to be evaluated in Part 2 of the study.
5.5.2
Rationale for Testing Lower Dose of BMS-813160
As the current 2 doses of BMS-813160, 600 QD and 300 BID, provide > 1-fold IC90 for CCR2/5 
function, the Sponsor proposes to add a lower dose of 150 mg QD and 300 mg QD for subjects 
with 2/3L MSS CRC that provides a trough concentration of 0.3 to 0.5-fold IC90 for inhibiting 
CCR2/5 function. See Section 3.1.6 for further details.
5.5.3
Rationale for Dose Selection of FOLFIRI
FOLFIRI will be given as per standard of care for metastatic CRC. Please see Section 7 for dosing 
and dose modifications. Bevacizumab or its biosimilar can be added to FOLFIRI for 2L therapy if 
it is available locally and appropriate as per investigator discretion. Bevacizumab or its biosimilar 
Revised Protocol No.: 06
Date: 05-Dec-2019
73
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
should be held for biopsies for at least 14 days or according to institutional guidelines to prevent 
any bleeding or delay in wound healing.
5.5.4
Rationale for Dose Selection of Gemcitabine/Nab-Paclitaxel
Gemcitabine/nab-paclitaxel will be given as per standard of care for metastatic pancreatic cancer. 
Please see Section 7 for dosing and dose modifications.
5.5.5
Rationale for Dose Selection of Nivolumab
Nivolumab 240 mg Q2W has been approved in many countries for use as monotherapy in patients 
with melanoma, RCC, NSCLC, and other indications. The safety and efficacy of the 480 mg Q4W 
flat dose of nivolumab are expected to be similar to the approved nivolumab dose of 240 mg flat 
doses or 3 mg/kg Q2W. The nivolumab dose of 480 mg Q4W was selected based on clinical data
and modeling and simulation approaches using PPK and exposure-response analyses of data from 
studies in multiple tumor types (melanoma, NSCLC, and RCC) where body weight normalized 
dosing (mg/kg) has been used. The PPK analyses have shown that exposure to nivolumab 
increased dose proportionally over the dose range of 0.1 to 10 mg/kg administered Q2W, and no 
clinically meaningful differences in PK across ethnicities and tumor types were observed. 
Nivolumab CLR and volume of distribution were found to increase as the body weight increases, 
but less than proportionally with increasing weight, indicating that milligram per kilogram dosing 
represents an over-adjustment for the effect of body weight on nivolumab PK. Using the PPK 
model, the overall distributions of nivolumab average steady state exposures are comparable after 
treatment with either nivolumab 3 mg/kg Q2W or nivolumab 480 mg Q4W, although the flat dose 
regimen of 480 mg Q4W is predicted to result in approximately 40% higher Cmaxss and 
approximately 20% lower steady-state trough concentrations compared to the reference regimen 
of 3 mg/kg Q2W. Across the various tumor types in the clinical program, nivolumab has been 
shown to be safe and well tolerated up to a dose level of 10 mg/kg, and the relationship between 
nivolumab exposure produced by 3 mg/kg and efficacy and safety has been found to be relatively 
flat. Although nivolumab Cmaxss is predicted to be higher following 480 mg Q4W, these 
exposures are predicted to be lower than or within the exposure ranges observed at doses up to 
10 mg/kg Q2W used in the nivolumab clinical program and are not considered to put patients at 
increased risk. The exposures predicted following administration of nivolumab 480 mg Q4W are 
on the flat part of the exposure-response curves for previously investigated tumors (melanoma and 
NSCLC) and are not predicted to affect efficacy. Based on these data, nivolumab 480 mg Q4W is 
expected to have similar efficacy and safety profiles to nivolumab 3 mg/kg Q2W.
Of note, as an immunoglobulin G4 (IgG4) monoclonal antibody, nivolumab does not interact 
directly with cytochrome P450 (CYP) enzyme systems. Systemic cytokine modulation data 
indicated that there were no meaningful changes in cytokines known to have indirect effects on 
CYP enzymes across all dose levels of nivolumab (0.3, 2, and 10 mg/kg) during the course of 
treatment. Therefore, it is unlikely that nivolumab administered at either 240 mg Q2W or 480 mg 
Q4W will affect the systemic exposures of BMS-813160.
Revised Protocol No.: 06
Date: 05-Dec-2019
74
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
5.5.6
Rationale for Nivolumab 30-minute Infusion
Long infusion times place a burden on participants and treatment centers. Establishing that 
nivolumab can be safely administered using shorter infusion times of 30 minutes duration in 
participants will diminish the burden provided no change in safety profile. Nivolumab has been 
administered safely at doses ranging up to 10 mg/kg over these treatment durations. Overall, 
infusion reactions including high-grade hypersensitivity reactions have been uncommon across 
multiple clinical studies, and all have been managed by following the safety algorithms. Infusion 
duration of 30 minutes for 480 mg nivolumab is not expected to present any safety concerns 
compared with the prior experience at 10 mg/kg nivolumab dose infused over the 60-minute 
duration. Nivolumab 480 mg Q4W infused over 30 minutes was FDA approved in Mar-2018 for 
the majority of the approved indications.
5.6
Treatment Duration
Participants will be treated until disease progression, intolerance to treatment, meeting 
discontinuation criteria, or withdrawal of consent. Participants who discontinue chemotherapy in 
part or whole due to intolerance can continue BMS-813160 or BMS-813160 and nivolumab 
(Cohort 3b) on study after investigator’s discussion with the Medical Monitor or Sponsor designee. 
Participants in Arm C will be permitted to continue on study treatment beyond initial 
RECIST v1.1-defined PD as long as they meet the criteria described in Section 7.4.8. Participants 
in Cohort 1c may also be able to cross over as described in Section 5.1.4. Participants will continue 
to get all study evaluations as per schedule of events in Table 2-3, Table 2-4, Table 2-5, and Table 
2-6.
Revised Protocol No.: 06
Date: 05-Dec-2019
75
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
6
STUDY POPULATION
For entry into the study, the following criteria MUST be met.
6.1
Inclusion Criteria
1) Signed Written Informed Consent
a) The participant must sign the ICF prior to the performance of any study related procedures 
that are not considered part of standard of care.
2) Type of Participant and Target Disease Characteristics
a) Participants with a histological or cytological confirmed diagnosis of an advanced solid 
tumor as defined below.
b) In general, discontinuation of 1 drug in a multi-drug regimen and continuation of other 
drug(s) are considered 1 line of treatment. Switching from IV (5-FU) to an oral formulation 
(capecitabine) of the same drug is also considered one line.
i)
Part 1 (Phase 1b)
1. Arm A: Metastatic CRC previously untreated or recurring systemically after 
surgery or > 6 months post adjuvant therapy. Local recurrence alone not allowed.
2. Arm B: Metastatic pancreatic adenocarcinoma previously untreated or recurring 
systemically after surgery or > 6 months post neoadjuvant/adjuvant therapy. Local 
recurrence alone not allowed.
3. Arm C: Metastatic pancreatic adenocarcinoma previously treated with 1 line of 
systemic chemotherapy or progressing on or within 6 months after 
neoadjuvant/adjuvant therapy. Locally advanced pancreatic adenocarcinoma which 
has progressed to metastatic disease previously treated with 1 line of systemic 
therapy is allowed.
- OR -
Metastatic MSS colorectal adenocarcinoma treated with systemic chemotherapy in 
the metastatic setting. Participants must have received an oxaliplatin-containing 
regimen and an irinotecan- containing regimen (or a combined oxaliplatin- and 
irinotecan-containing regimen) but no more than 2 lines of systemic chemotherapy 
for metastatic disease. Chemotherapy administered in the adjuvant setting is 
considered a line only if there was disease progression within 6 months after 
completion of the adjuvant therapy. (Note: MSS is defined as expression of MLH1, 
MSH2, MSH6 and PMS2 by immunohistochemistry [IHC] or absence of instability 
in microsatellite markers by PCR as determined by local laboratory.) Patients who 
are tested by PCR and found to be MSI-low can enroll on this arm.
ii) Part 2 (Phase 2)
1. Not applicable per Protocol Revision 03. Arm A - Cohort 1 (1L Colorectal): 
Metastatic CRC previously untreated or recurring systemically after surgery or 
> 6 months post adjuvant therapy. Local recurrence alone not allowed.
2. Not applicable per Protocol Revision 03. Arm A - Cohort 2 (3L Colorectal): 
Metastatic CRC treated with no more than 2 lines of systemic chemotherapy for 
metastatic disease. Adjuvant chemotherapy or radiation is not considered 1L if 
more than 6 months from completion of therapy. Progression on or shortly after 
Revised Protocol No.: 06
Date: 05-Dec-2019
76
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
FOLFIRI required, but it does not have to be the last treatment given. Participants 
must have also received an oxaliplatin-containing regimen (including as part of a 
combined oxaliplatin- and irinotecan-containing regimen). This may include 
chemotherapy administered in the adjuvant setting only if there was disease 
progression within 6 months after completion of the adjuvant therapy. 
3. Not applicable per Protocol Revision 03. Arm B - Cohort 3 (1L Pancreatic): 
Metastatic pancreatic adenocarcinoma previously untreated or recurring 
systemically after surgery or > 6 months post adjuvant therapy. Local recurrence 
alone not allowed. 
4. Not applicable per Protocol Revision 03. Arm C - Cohort 4 (2L Pancreatic): 
Metastatic pancreatic adenocarcinoma previously treated with 1 line of systemic 
chemotherapy or progressing on or within 6 months after adjuvant therapy. Locally 
advanced pancreatic adenocarcinoma which has progressed to metastatic disease 
previously treated with 1 line of therapy is allowed. 
5. Not applicable per Protocol Revision 03. Arm C - Cohort 5 (2L or 3L Colorectal): 
Metastatic MSS colorectal adenocarcinoma treated with 1 or 2 prior lines of 
systemic chemotherapy in the metastatic setting. Participants must have received 
an oxaliplatin-containing regimen and an irinotecan-containing regimen (including 
as part of a combined oxaliplatin- and irinotecan-containing regimen). This may 
include chemotherapy administered in the adjuvant setting only if there was disease 
progression within 6 months after completion of the adjuvant therapy. (Note: MSS 
is defined as expression of MLH1, MSH2, MSH6 and PMS2 by 
immunohistochemistry [IHC] or absence of instability in microsatellite markers by 
PCR as determined by a local laboratory.) 
6. Not applicable per Protocol Revision 03. Arm C - Cohort 6 (MSI-high
colorectal): Metastatic MSI-high colorectal adenocarcinoma progressed after anti-
PD1/PDL1 therapy, and previously treated with a fluoropyrimidine, an oxaliplatin-
containing regimen, and an irinotecan containing regimen (including as part of a 
combined oxaliplatin- and irinotecan-containing regimen). This may include 
chemotherapy administered in the adjuvant setting only if there was disease 
progression within 6 months after completion of the adjuvant therapy. (Note: 
MSI-high is defined as loss or expression of MLH1, MSH2, MSH6 or PMS2 by 
IHC or presence of instability in microsatellite markers by PCR as determined by a 
local laboratory.) Participants who are tested by PCR and found to be MSI-low are 
not allowed to be enrolled on this arm but can enroll on MSS arm. 
7. Arm A - Cohorts 1a, 1b, and 1c (2L Colorectal): Metastatic CRC previously treated 
with 1 line of oxaliplatin-based systemic therapy in the metastatic setting or 
progression on or within 6 months of adjuvant oxaliplatin based chemotherapy.
Adjuvant chemotherapy for CRC or neoadjuvant chemoradiation for rectal cancer 
is not considered a line if more than 6 months from completion of such therapy.
8. Arm B - Cohorts 3a, 3b, and 3c (1L Pancreatic): Metastatic pancreatic 
adenocarcinoma previously untreated or recurring systemically after surgery or 
> 6 months post neoadjuvant/adjuvant therapy. Local recurrence alone not allowed.
9. Arms C and D - Cohort 4 (Cohort 4 closed per Revised Protocol 06) and 7 (2L
Pancreatic): Metastatic pancreatic adenocarcinoma previously treated with 1 line 
Revised Protocol No.: 06
Date: 05-Dec-2019
77
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
of 
systemic 
therapy
or 
progressing 
on 
or 
within 
6 
months 
after 
neoadjuvant/adjuvant therapy. Locally advanced pancreatic adenocarcinoma which 
has progressed to metastatic disease previously treated with 1 line of systemic 
therapy is allowed. Chemotherapy in the neoadjuvant or adjuvant setting is not 
considered a line if progression occurred more than 6 months after completion of 
therapy.
10. Arms C and D - Cohort 5 and 8 (2L or 3L Colorectal): Metastatic MSS colorectal 
adenocarcinoma treated with systemic therapy in the metastatic setting. Participants 
must have received an oxaliplatin-containing regimen and an irinotecan-containing 
regimen or a combined oxaliplatin- and irinotecan-containing regimen but no more 
than 2 lines of systemic chemotherapy for metastatic disease. Chemotherapy 
administered in the adjuvant setting is considered 1 line only if there was disease 
progression within 6 months after completion of the adjuvant therapy. (Note: MSS 
is defined as expression of MLH1, MSH2, MSH6 and PMS2 by 
immunohistochemistry [IHC] or absence of instability in microsatellite markers by 
PCR as determined by a local laboratory.)
3) General Inclusion Criteria
a) Participants must have measurable disease by RECIST v1.1 (Appendix 5).
b) Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
c) Ability to swallow tablets or capsules.
d) All participants will be required to undergo mandatory pre and on-treatment biopsies. If a 
participant had a biopsy in the preceding 90 days with no intervening anti-cancer therapy, 
participants can be enrolled without needing a repeat biopsy after discussion with the 
Medical Monitor and availability of formalin-fixed paraffin embedded (FFPE) blocks or 
unstained slides as delineated below. Participants will however be required to undergo on-
treatment biopsy at acceptable clinical risk as judged by the investigator in all arms.
i)
Pre-treatment tissue must be collected and centrally or locally confirmed for adequate 
tissue quantity and quality during the screening period prior to first dose of study 
treatment. Please refer to lab manual for detailed biopsy collection instructions. Up to 
15% of treated participants in each arm may be enrolled without confirmation of 
adequate tissue, after discussion with the Medical Monitor. 
ii) The tumor tissue specimen must be a core needle biopsy, excisional or incisional 
biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or punch 
biopsies are not considered adequate for biomarker review. Biopsies of bone lesions 
that do not have a soft tissue component or decalcified bone tumor samples are also not 
acceptable. Where possible, the biopsied lesion should be distinct from target lesions 
being evaluated for radiologic response, and the same lesion should be used for both 
the baseline and on-treatment sampling.
e) Adequate marrow function as defined by the following: 
i)
White blood cell (WBC) ≥2000/μL; > 1500/μL allowed for Arms C and D
ii) Neutrophils ≥1500/μL; > 1000/μL allowed for Arms C and D
iii) Platelets ≥100 × 103/μL; > 75,000/μL allowed for Arms C and D
iv) Hemoglobin ≥8.5 g/dL
Revised Protocol No.: 06
Date: 05-Dec-2019
78
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
f)
Adequate other organ functions as defined by the following: 
i)
Alanine aminotransferase (ALT)
and (aspartate aminotransferase) AST d 3x
institutional upper limit of normal (ULN)
ii) Total bilirubin d 1.5x institutional ULN (except participants with Gilbert’s Syndrome 
who must have normal direct bilirubin) 
iii) Serum creatinine d 1.5x ULN or creatinine clearance (CrCl) t 40 mL/min (measured 
using the Cockcroft-Gault formula below): 
Female CrCl ൌሺ140 െܽ݃݁݅݊ݕ݁ܽݎݏሻൈݓ݄݁݅݃ݐ݅݊݇݃ൈ0.85
72 ൈserum creatinine in mg/dL
Male CrCl ൌሺ140 െܽ݃݁݅݊ݕ݁ܽݎݏሻൈݓ݄݁݅݃ݐ݅݊݇݃ൈ1.00
72 ൈserum creatinine in mg/dL
g) Ability to comply with study visits, treatment, procedures, PK and PD sample collection, 
and required study follow-up. 
4) Age and Reproductive Status
a) Males and Females, ages 18 or age of majority or older at the time of consent
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic 
gonadotropin [HCG]) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential (WOCBP) must agree to follow instructions for 
method(s) of contraception (defined in Appendix 04 and study ICF) for the duration of 
study therapy plus 10 months after completion of treatment.
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception (Appendix 4) for the duration of study therapy plus 7 months
post-treatment completion. In addition, male participants must be willing to refrain from 
sperm donation during this time (see Appendix 4).
f)
Azoospermic males are exempt from contraceptive requirements. WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
and still must undergo pregnancy testing as described in this section. Continuous 
abstinence must begin at least 30 days prior to initiation of study therapy (see Appendix 4).
g)
WOCBP are permitted to use hormonal contraception methods as described in 
Appendix 4.
Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception, which have a 
failure rate of < 1% when used consistently and correctly (see Appendix 4).
The investigator is responsible for review of medical history, menstrual history, and recent sexual 
activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Revised Protocol No.: 06
Date: 05-Dec-2019
79
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
6.2
Exclusion Criteria
1) Target Disease Exceptions
a) Histology other than adenocarcinoma (neuroendocrine or acinar cell). If mixed tumor, the 
predominant histology must be adenocarcinoma.
b) Suspected, known, CNS metastases (Imaging required only if participants are 
symptomatic). Participants with adequately treated CNS metastasis are eligible if the 
participant’s neurologic function returned to baseline and are not currently on steroids for 
at least 2 weeks prior to study entry. Participants with history of brain metastasis require 
baseline MRI of the brain prior to study entry.
2) Medical History and Concurrent Diseases
a) Participants with active, known or suspected autoimmune disease. Participants with 
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition 
only requiring hormone replacement, euthyroid participants with a history of Grave’s 
disease (participants with suspected autoimmune thyroid disorders must be negative for 
thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin 
prior to first dose of study treatment), psoriasis not requiring systemic treatment, or 
conditions not expected to recur in the absence of an external trigger are permitted to enroll
after discussing with the Medical Monitor.
b) Participants with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 
14 days of study treatment administration except for adrenal replacement steroid doses 
> 10 mg daily prednisone equivalent in the absence of active autoimmune disease. 
Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating 
study treatment is permitted.
c) Interstitial lung disease that is symptomatic or may interfere with the detection or 
management of suspected treatment-related pulmonary toxicity.
d) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the 
following:
i)
Myocardial infarction or stroke/transient ischemic attack within the past 6 months
ii) Uncontrolled angina within the past 3 months
iii) Any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation, or torsades de pointes)
iv) Not applicable per Protocol Revision 04. QT interval corrected for heart rate using 
Fridericia’s formula (QTcF) prolongation > 480 msec. 
v) History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification III-IV, 
pericarditis, significant pericardial effusion, or myocarditis)
vi) Cardiovascular disease-related requirement for daily supplemental oxygen therapy
e) History of any chronic hepatitis as evidenced by the following:
i)
Positive test for hepatitis B surface antigen
ii) Positive test for qualitative hepatitis C viral load (by PCR)
Revised Protocol No.: 06
Date: 05-Dec-2019
80
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Note: Participants with positive hepatitis C antibody and negative quantitative hepatitis C 
by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion 
criterion.
f)
Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric, 
colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless a complete 
remission was achieved at least 2 years prior to study entry AND no additional therapy is 
required during the study period. 
g) Other active malignancy requiring concurrent intervention.
h) Prior organ allograft or allogeneic bone marrow transplantation. 
i)
Any major surgery within 4 weeks of study treatment. Participants must have recovered 
from the effects of major surgery or significant traumatic injury at least 14 days before the 
first dose of study treatment.
j)
All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must 
have resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for 
Adverse Events [NCI CTCAE] v4.03) or baseline before administration of study treatment. 
Participants with toxicities attributed to prior anti-cancer therapy that are not expected to 
resolve and result in long lasting sequelae, such as neuropathy after platinum-based 
therapy, are permitted to enroll.
k) Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or 
anti-fungal therapy ≤7 days prior to administration of study medication.
l)
Known history of testing positive for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (Testing for HIV must be performed at sites 
mandated by local requirements)
m) Any significant acute or chronic medical illness which in the opinion of the investigator is 
detrimental for participation on the trial.
n) Current or recent (within 3 months of study treatment administration) gastrointestinal 
disease that could impact upon the absorption of study treatment
o) Any gastrointestinal surgery that is likely impact upon the absorption of study treatment. 
Whipple or other upper GI surgery is allowed if there is no clinical evidence of 
malabsorption.
p) Not applicable per Protocol Revision 04. Inability to tolerate oral medication. 
q) Not applicable per Protocol Revision 04. Inability to be venipunctured and/or tolerate 
venous access. 
r)
Participants who have received a live / attenuated vaccine within 30 days of first treatment.
3) Prior Therapy
a) Prior treatment with CCR2 and/or CCR5 inhibitors, PD-1, PD(L)-1 or cytotoxic 
T-lymphocyte antigen-4 (CTLA-4) antibodies
b) Any anti-cancer therapy (eg, chemotherapy, biologics, vaccines, or hormonal treatment) 
including investigational drugs within 4 weeks prior to the first dose of study treatment
administration, except for non-cytotoxic therapies, for which at least 4 weeks or 5 half-lives 
(whichever is shorter) must have elapsed between last dose and first treatment with any 
Revised Protocol No.: 06
Date: 05-Dec-2019
81
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
study treatments; if 5 half-lives is shorter than 4 weeks, agreement with the Medical 
Monitor must be obtained.
4) Restricted Concomitant Therapy
a) Prior use of strong/moderate CYP3A4 inhibitors or inducers within 4 weeks or 5 half-lives 
(whichever is shorter) prior to the first dose of BMS-813160. (See Appendix 8).
b) For Part 1 only: MATE inhibitors within 4 weeks or 5 half-lives (whichever is shorter) 
prior to the first dose of BMS-813160 and for the first 2 weeks of BMS-813160 
monotherapy. (See Appendix 9).
c) Prior use of strong inhibitors of UGT1A1 in FOLFIRI arm within 4 weeks or 5 half-lives 
(whichever is shorter) prior to starting FOLFIRI (see Appendix 10) or participants with 
known UGT1A1 deficiency is prohibited.
d) Not applicable per Revised Protocol 06. Class I antiarrhythmics (eg, quinidine, 
procainamide, dysopiramide, lidocaine, phenytoin, mexiletine, tocainide, flecainide, 
propafenone, and moricizine)
e) Class 1A antiarrhythmics (eg, quinidine, procainamide, dysopiramide) are prohibited
f)
Class 1C antiarrhythmics (eg, flecainide, propafenone, and moricizine) are prohibited.
g) Tricyclic antidepressants are prohibited.
h) Caution is warranted with concomitant use with Class 1B antiarrhythmics (lidocaine, 
phenytoin, mexiletine, tocainide) and methadone (in particular at high doses) due to 
potential sodium channel blockade.
5) Physical and Laboratory Test Findings
a) Ascites needing paracentesis or medical management (Grade 2 or higher)
b) Peripheral Neuropathy greater than Grade 1 for Arm B receiving nab-paclitaxel
c) Albumin less than 3 g/dL (pancreatic cancer arms only)
d) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG or clinical laboratory determinations beyond what 
is consistent with the target population
e) Any of the following on 12-lead ECG prior to study treatment administration, confirmed 
by repeat
i)
QRS ≥120 msec, except right bundle branch block or intraventricular conduction delay 
which is not considered clinically significant
ii) QTcF ≥480 msec, except right bundle branch block
6) Allergies and Adverse Drug Reaction
a) History of allergy to study treatments or any of its components of the study arm that 
participant is enrolling
7) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances, and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply and BMS approval is required.)
Revised Protocol No.: 06
Date: 05-Dec-2019
82
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
6.3.1
Meals and Dietary Restrictions
Study treatment should be taken at approximately the same time each day. For participants in 
Part 1, during the first 6 weeks of study treatment when the intensive PK samples are collected on 
C0D1, C0D14 (Arms A, B, and C), C1D15 (Arm B), and C2D1 (Arm A), and for a subset of 
participants in Part 2 (Arms A and B) on Cycle 2 Day 1 when the intensive PK samples are 
collected, participants are required to fast for at least 8 hours prior to the collection of specimens 
for PK analysis. Light meal (total calories: ~330 kcal, fat ≤15%, protein ≤10%) can be allowed 
2 hour post dose (eg, participants may receive study treatment at 7:00/8:00 AM and eat breakfast 
at 9:00/10:00 AM). For evening doses (if applicable), no food is allowed 2 hour prior to or 2 hour 
after dose (eg, participants may eat dinner at 5:00/6:00 PM and receive study treatment at 7:00/8:00 
PM). After 6 weeks in Part 1 and other than Cycle 2 Day 1 for a subset of participants in Part 2, 
where intensive PK samples are collected, BMS-813160 can be taken regardless of food intake.
6.3.2
Caffeine, Alcohol, and Tobacco
No restrictions.
6.3.3
Activity
No restrictions.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants, to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements, as applicable, and to respond to queries 
from regulatory authorities.
6.4.1
Retesting During Screening or Lead-In Period
Participant Re-enrollment: This study permits the re-enrollment of a participant that has 
discontinued the study as a screen failure. If re-enrolled, the participant must be re-consented.
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory value).
The most current result prior to enrollment is the value by which study inclusion will be assessed, 
as it represents the participant’s most current, clinical state.
Revised Protocol No.: 06
Date: 05-Dec-2019
83
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Laboratory parameters and/or assessments that are included in Table 2-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
Revised Protocol No.: 06
Date: 05-Dec-2019
84
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
7
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device intended to be administered to a study participant according to the study treatment 
assignment.
Study 
treatment
includes 
both 
Investigational 
[Medicinal] 
Product 
(IP/IMP) 
and 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
An investigational product, also known as investigational medicinal product in some regions, is 
defined as a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
non-investigational products.
Study treatment descriptions including dosage form, potency, IP/non-IMP, and storage conditions 
are presented in Table 7-1.
Revised Protocol No.: 06
Date: 05-Dec-2019
85
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 7-1:
Study Treatments for CV202103
Product Description / Class and 
Dosage Form
Potency
IP/Non-IMPa
Blinded or
Open Label
Packaging / 
Appearance
Storage Conditions
(per label)
BMS-813160-01 Capsule
150 mg
IP
Open-label
Capsule
2 to 25°C, Store in a tightly 
closed container
BMS-813160-01 Tablet
300 mg
IP
Open-label
Film Coated Tablet
2 to 25°C, Store in a tightly 
closed container
BMS-813160-01 Tablet
75 mg
IP
Open-label
Film Coated Tablet
2 to 25°C, Store in a tightly 
closed container
Nivolumab (BMS-936558)
Solution for injectionb
100 mg/vial (10 mg/mL)
IP
Open-label
Vial
2 to 8°C, Protect from light and 
freezing
Nivolumab (BMS-936558)
Solution for injectionb
40 mg/vial (10 mg/mL)
IP
Open-label
Vial
2 to 8°C, Protect from light and 
freezing
Gemcitabine
Concentrate for Solution for Injectionc
1000 mg/vial and various 
strengths
IP
Open-label
Vial and various 
packaging configurations
Refer to the label on container 
or package insert / summary of 
product characteristics
Nab-paclitaxel (ABRAXANE)
Concentrate for Solution for Injectionc
100 mg/vial and various 
strengths
IP
Open-label
Vial and various 
packaging configurations
Refer to the label on container 
or package insert / summary of 
product characteristics
5-FU Solution for Injectionc
Various strengths
IP
Open-label
Vial and various 
packaging configurations
Refer to the label on container 
or package insert / summary of 
product characteristics
Leucovorin Solution for Injectionc
Various strengths
IP
Open-label
Vial and various 
packaging configurations
Refer to the label on container 
or package insert / summary of 
product characteristics
Irinotecan Solution for Injectionc
Various strengths
IP
Open-label
Vial and various 
packaging configurations
Refer to the label on container 
or package insert / summary of 
product characteristics
Abbreviations: 5-FU = 5-fluorouracil; IP = investigational product; Non-IMP = non-investigational medicinal product
a Where allowed by local regulations, chemotherapy treatments may be considered Non-IMP.
b Nivolumab (BMS-936558) will be supplied as a 240 mg kit - each kit containing (2) 100 mg vials and (1) 40 mg vial.
c These products will be obtained as local commercial product in countries if allowed by local regulations or through investigating site’s standard prescribing 
procedures, otherwise the Sponsor will supply these products.
Revised Protocol No.: 06
Date: 05-Dec-2019
86
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
7.1
Treatments Administered
The selection and timing of dose for each participant are presented in Table 7.1-1.
Table 7.1-1:
Selection and Timing of Dose
Study Treatment
Dosage level(s)
Frequency of Administration
Route of
Administration
BMS-813160
(150 mg capsule or
300 mg tablet)
300 mg
BID
PO
BMS-813160
(150 mg capsule or
300 mg tablet)
600 mg
QD
PO
BMS-813160
(150 mg capsule or
75 mg tablet)
150 mg
QD
PO
BMS-813160
(150 mg capsule or
300 mg tablet)
300 mg
QD
PO
Nivolumab
480 mg IV
Q4W
IV infusion
5-FU
400 mg/m2 Bolus
AND
2400 mg/m2 IV
Day 1, 15: Q4W
Bolus and IV infusion
Leucovorin
400 mg/m2 IV
Day 1, 15: Q4W
IV infusion
Irinotecan
180 mg/m2 IV
Day 1, 15: Q4W
IV infusion
Gemcitabine
1000 mg/m2 IV
Day 1, 8, 15: Q4W
IV infusion
Nab-paclitaxel
(ABRAXANE)
125 mg/m2 IV
Day 1, 8, 15: Q4W
IV infusion
Abbreviations: 5-FU = 5-fluorouracil; BID = twice a day; IV = intravenous; PO = per os (by mouth [orally]); Q4W = 
every 4 weeks; QD = once daily
FOLFIRI (irinotecan 180 mg/m2 over 90 minutes; leucovorin 400 mg/m2 over 2 hours (leucovorin 
may be given concurrently with irinotecan); 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 over 
46 hours continuous infusion) on Days 1 and 15 of a 28-day cycle. Bevacizumab or its biosimilar 
can be added to 2L FOLFIRI if appropriate, and will be administered in accordance with local 
Health Authority approved labeling for these agents. Levoleucovorin can be substituted for 
leucovorin as per site’s standard practice.
The recommended dose of nab-paclitaxel (ABRAXANE) is 125 mg/m2 administered as an 
intravenous infusion over 30 to 40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer 
gemcitabine 1000 mg/m2 over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 
Revised Protocol No.: 06
Date: 05-Dec-2019
87
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
15 of each 28-day cycle. Participants in Cohort 3b will be administered nivolumab first and 
followed by chemotherapy 30 minutes later.
Nivolumab 480 mg administered as an intravenous infusion over 30 minutes every 4 weeks.
Restrictions related to food and fluid intake are described in Section 6.3.1.
On days when PK blood samples or pre-dose ECGs are required, participants will take the morning 
dose of BMS-813160 at the clinic after all required samples and ECGs are collected and start of 
infusion if applicable. Please refer to Table 9.5.1-1, Table 9.5.2-1, Table 9.5.3-1, Table 9.5.4-1, 
and Table 9.5.4-2. On days PK samples or ECGs are not required, BMS-813160 can be taken at 
home or in clinic. Please see Section 6.3.1 for dietary restrictions during the first 6 weeks for 
participants in Part 1 when the intensive PK samples are collected, and on Cycle 2 Day 1 for a 
subset of participants with the intensive PK collection in Part 2 (Arms A and B).
Participants will receive FOLFIRI and Gem/nab-paclitaxel as per their site standard of care. All 
supportive care treatments including prophylactic treatment for nausea, diarrhea and infusion 
reaction will be given as per standard of care.
For participants on the nivolumab treatment, a 30-minute infusion of nivolumab will be followed 
by a 30-minute observation period, after all infusions for each participant.
7.2
Method of Treatment Assignment
Study treatment will be dispensed at the study visits as listed in Schedule of Activities (Section 2).
All participants must be assigned a participant number upon providing signed written informed 
consent. Based on the rate of participant enrollment, the Sponsor will implement an interactive
response technology (IRT) to assign participant numbers, study treatment group and dose level, as 
well as manage treatment supply. During the screening visit, the investigative site will register the 
participant by an IRT designated by BMS for assignment of a 5-digit participant number that will 
be unique across all sites. Enrolled participants, including those not dosed, will be assigned 
sequential participant numbers starting with 
 for example, 
.
The PID will ultimately be composed of the site number and participant number. Specific 
instructions for using the IRT will be provided to the investigational sites in a separate instruction 
manual.
Each participant who is randomized will be assigned a unique randomization number. This is not 
the primary identifier for the participant, but is used for the randomization schedule. The primary 
identifier will be the PID described above, for use on the case report form (CRF) and source 
documents. A participant being reassigned to an Arm C cohort from another cohort will be 
assigned a different treatment assignment but will retain the same PID.
For Part 1, the first 3 participants will be enrolled into 1 dose cohort in each arm. Once 
approximately 3 participants enroll, the arm will enroll approximately another 3 participants to the 
other dose cohort in the same arm. For example, 3 participants in Arm A will be enrolled into the 
300 mg BID dosing. The next 3 participants will be enrolled into the 600 mg daily arm. Participants
will be followed for 6 weeks to assess DLTs for each dose and schedule. Participants will not be 
Revised Protocol No.: 06
Date: 05-Dec-2019
88
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
replaced if they are discontinued from the study secondary to a DLT unless the AE can be 
determined to be unrelated to treatment or not a DLT.
For Part 2, participants in Arm A will be randomized in a 1:1:1 ratio to FOLFIRI in combination 
with BMS-813160 300 mg BID or FOLFIRI in combination with BMS-813160 150 mg QD, or 
FOLFIRI alone. Participants in Arm B will also be randomized in a 1:1:1 ratio to BMS-813160 
300 mg BID in combination with Gem/nab-paclitaxel or BMS-813160 300 mg BID in 
combination with Gem/nab-paclitaxel and nivolumab, or Gem/nab-paclitaxel alone. Stratification 
by tumor location and prior treatment in Arms A and B, respectively, was planned, but in error 
was omitted from the IRT system. As the cohorts were largely enrolled when the error was 
discovered, stratification was removed from the protocol with Revised Protocol 06. All of the 
planned stratification factors have been collected and can be analyzed retrospectively; thus, the 
lack of stratification is not expected to affect the scientific validity of the study. BMS will create 
a randomization schedule that will be uploaded into the IRT.
7.3
Blinding
This is an open-label randomized study. Once participants are randomized, designated personnel 
of the Sponsor will have access to randomization assignments prior to database lock to facilitate 
data analysis (see Section 10.3.9).
7.4
Dosage Modification
7.4.1
Dose Limiting Toxicity
For the purpose of guiding dose regimen, DLTs will be defined based on the incidence, duration 
and grade of AEs for which no alternate cause can be identified. AEs will be evaluated according 
to the NCI CTCAE v4.03. The incidence of DLT(s) during the first 6 weeks of treatment in Part 1 
(the DLT evaluation period) and 4 weeks for Part 2 will be used. Every attempt must be made to 
assign relationship to BMS-813160, to the chemotherapy or nivolumab regimen, or to both. DLTs
are toxicities that are attributed to BMS-813160 or the combination regimen. Toxicities that are 
well recognized and expected with the chemotherapy backbone, will not automatically be counted 
as dose limiting. Also, to meet criteria for dose limiting, AEs have to be related to study treatment, 
and not to disease progression, be clinically relevant, and a clinically relevant shift from baseline. 
Consideration will be given to a participant’s tolerability during the lead-in phase (BMS-813160 
alone) and discussed with the Medical Monitor. Participants experiencing a DLT may be treated 
at 1 dose reduction as long as they recover from the toxicity, do not meet discontinuation criteria, 
and it is in the best interest of the participant as per the treating physician and discussed with the 
Medical Monitor. Participants who withdraw from the study during the DLT evaluation interval 
for reasons other than a DLT may be replaced at the same dose of BMS-813160. The total DLT 
period is 6 weeks in Part 1 and 4 weeks in Part 2, and participants must have received at least 75% 
of the BMS-813160 doses and 1 dose of chemotherapy/nivolumab with observation for a minimum 
of 21 days following the first combination treatment dose to be considered evaluable for DLT.
In Part 1, within each dose level per arm, if 0 or 1 out of the first 3 participants experience a DLT, 
then an additional 3 participants will be enrolled as planned. If 2 out of 6 participants experience 
a DLT, the cohort will be expanded to 9 participants. If the observed DLT rate is less than 33% 
Revised Protocol No.: 06
Date: 05-Dec-2019
89
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
and the number of DLT-evaluable subjects treated at a dose is approximately 6 subjects or more, 
then the dose level is deemed to be tolerable. If ≥2 of 3 or ≥3 of 6 or 9 participants experience 
DLTs within a dose cohort during the DLT evaluation interval, then that dose level or combination 
will be determined to be not tolerated, and 1 level lower or alternate treatment schedules will be 
explored after a discussion between the investigators and the Sponsor.
DLTs can include the following AEs (meeting the preceding criteria):
1) Hepatic DLT
a) Any of the following events will be considered a hepatic DLT:
i)
Any ≥Grade 3 elevation of AST, ALT, or total bilirubin
ii) Grade 2 AST or ALT with symptomatic liver inflammation (eg, right upper quadrant 
tenderness, jaundice, pruritus)
iii) AST or ALT > 3x ULN and concurrent total bilirubin > 2x ULN without initial findings 
of cholestasis (elevated serum alkaline phosphatase, eg, findings consistent with Hy’s 
law or FDA definition of potential drug-induced liver injury [DILI])*
*Note that this special category of DLT uses ULN rather than Common Toxicity 
Criteria Grade for definition.
2) Hematologic DLT
a) Grade 4 neutropenia ≥7 days in duration
b) Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement 
for platelet transfusion
c) Grade ≥3 febrile neutropenia
d) Grade ≥3 hemolysis (ie, requiring transfusion or medical intervention such as steroids)
e) Grade 4 anemia not explained by underlying disease
3) Nonhepatic Nonhematologic DLT
a) Any of the following events will be considered a nonhepatic nonhematologic DLT:
i)
Grade 2 or greater episcleritis, uveitis, or iritis 
ii) Any other Grade 2 eye pain or blurred vision that does not respond to topical therapy 
and does not improve to Grade 1 severity within 2 weeks OR requires systemic 
treatment
iii) Grade 2 myocarditis
iv) Grade 3 pneumonitis, bronchospasm, or neurologic toxicity requires discontinuation
v) Any Grade 3 or greater nondermatologic, nonhepatic, nonhematologic toxicity will be 
considered a DLT with the following specific EXCEPTIONS:
(1) Grade 3 electrolyte or laboratory abnormalities that are not complicated by 
associated clinical adverse experiences, last less than 48 hours and either resolve 
spontaneously or respond to conventional medical intervention
(2) Grade 3 nausea, vomiting, or diarrhea that lasts less than 48 hours and either 
resolves spontaneously or responds to conventional medical intervention
(3) Isolated Grade 3 or 4 asymptomatic elevation of amylase or lipase not associated 
with clinical or radiographic evidence of pancreatitis
Revised Protocol No.: 06
Date: 05-Dec-2019
90
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
(4) Isolated Grade 3 fever not
associated with hemodynamic compromise 
(eg, hypotension, clinical or laboratory evidence of impaired end-organ perfusion)
(5) Grade 3 endocrinopathy that is well-controlled by hormone replacement
(6) Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to site of 
known or suspected tumor)
(7) Grade 3 fatigue
(8) Grade 3 infusion reaction that returns to Grade 1 in less than 6 hours
4) Dermatologic DLT
a) Grade 3 rash if no improvement (ie, resolution to ≤Grade 1) after a 1- to 2-week dosing
delay. Participants who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity.
b) Grade 4 rash of any duration
7.4.1.1
Stopping Rules During Part 2
Continuous evaluation of toxicity events in the Part 2 cohorts will be performed. If at any time, 
the aggregate rate of treatment-related toxicities meeting DLT criteria in a cohort exceeds 33%, 
the findings will be discussed with the investigators and further enrollment may be interrupted. If 
a cohort is discontinued due to toxicity, a new cohort at a previously tested alternative dose level 
which was found to be safe in Part 1 may be considered based on the aggregate safety experience 
and in consultation and agreement between Investigators and Sponsor. A revised protocol 
reflecting any such new cohort will be submitted prior to enrollment to the cohort.
7.4.2
Management Algorithms for Immuno-oncology Agents
Immuno-oncology agents are associated with AEs that can differ in severity and duration from 
AEs caused by other therapeutic classes. Nivolumab and BMS-813160 are considered immuno-
oncology agents in this protocol. Early recognition and management of AEs associated with 
immuno-oncology agents may mitigate severe toxicity. Management algorithms have been 
developed from extensive experience with nivolumab and ipilimumab to assist investigators in 
assessing and managing the following groups of AEs:
•
Gastrointestinal
•
Renal
•
Pulmonary
•
Hepatic
•
Endocrinopathies
•
Skin
•
Neurological
•
Myocarditis
Revised Protocol No.: 06
Date: 05-Dec-2019
91
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Specific algorithms for the management of immune-related AEs are provided in Appendix 6 and 
are applicable to immune-related AEs for all immuno-oncology study treatment combinations.
7.4.3
General Guidelines for Dose Modifications
Participants will be monitored continuously for AEs while on study therapy. Participants will be 
instructed to notify their physician for any and all AEs. Dose modifications in this section for 
chemotherapy are meant as a general guidance. Modifications should be applied by the 
investigator’s judgment. In case of an AE relationship assignment to chemotherapy alone, dose 
modifications for chemotherapy alone are allowed. In case of doubt, both chemotherapy and 
BMS-813160 doses should be modified. Also, in case of assignment of AE relationship to 
BMS-813160 alone, dose reduction for chemotherapy is not mandated. Specific algorithms for the 
management of immune-related AEs are provided in Appendix 6 and are applicable to 
immune-related AEs for all immuno-oncology study treatment combinations. For chemotherapy 
agents, the package insert and local standard of care rules for dose reduction should also be applied.
Nivolumab dose modifications do not apply; nivolumab dose delays are described in Section 
7.4.7.1.
For common cumulative lower grade toxicity (Grade 2 or less) for chemotherapy 
(eg, neurotoxicity, fatigue, GI toxicity) ‘drug holidays’ are allowed after the DLT observation 
period in Part 1 and 2 cycles in Part 2 have been completed (and after consultation with the 
Sponsor’s Medical Monitor) when the investigator believes this is in the participant’s best interest. 
Restarting without dose modification is allowed upon recovery. Any laboratory only abnormalities 
without clinical manifestations or electrolyte abnormalities that may be managed with supplements 
also do not need dose modification.
For an AE requiring dose modification, BMS-813160, chemotherapy, and/or nivolumab should be 
interrupted to allow recovery from the AE. Re-initiation of study treatment cannot occur until the 
AE decreases to ≤Grade 1 or baseline assessment. In case of delayed recovery to ≤Grade 1 or 
baseline from treatment-related AEs that result in a delay of treatment for > 28 days, the participant 
will not receive additional protocol-related therapy and will be removed from study unless 
discussed and agreed upon by the Investigator and Sponsor/Medical Monitor that it is in the best 
interest of the participant to receive additional therapy with BMS-813160 and/or other study 
treatments.
7.4.4
BMS-813160 Dose Modifications
•
New onset of QTcF intervals > 500 msec or prolongation > 50 msec over baseline, new onset 
QRS intervals > 140 msec, new onset bundle branch block or symptomatic bradycardia, Type 2 
second or third-degree heart block will require dose interruption and restarting at 1 dose level 
lower when ECG changes resolve to baseline. Any electrolyte abnormalities should be 
corrected and ECG should be repeated with cardiology consultation if clinically indicated. 
•
Grade 3 non-hematologic toxicity or Grade 4 hematologic toxicity attributed to BMS-813160 
will require a dose delay until recovery and 1 dose level reduction.
Revised Protocol No.: 06
Date: 05-Dec-2019
92
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Any Grade 3 laboratory only abnormalities without clinical manifestations or electrolyte 
abnormalities that may be managed with supplementation can be managed with dose delay and 
do not automatically need dose modification.
•
Participants who hold BMS-813160 for less than 7 days for reasons other than drug toxicity
will skip those days and continue on BMS-813160 treatment for the rest of the cycle. 
•
Participants who hold BMS-813160 for more than 7 days or for drug toxicity will hold 
treatment for the remainder of the cycle and start at a reduced dose for the next cycle unless 
the delay was from chemotherapy alone or unrelated to study treatment.
•
Participants who miss a dose at the specified time can take it as long as there is 8 hour between 
doses for BID dosing and 16 hours for QD dosing. If less than 8 hours for BID dosing and 
16 hours for QD dosing, that dose should be skipped and noted in the participant pill diary.
•
Participants who have vomited a dose will not retake the dose unless the vomiting occurred 
within 15 minutes of taking the dose and intact capsules or tablets are seen. Otherwise, that 
dose will be skipped and participant will take BMS-813160 at the next scheduled time.
•
If chemotherapy or nivolumab is delayed due to toxicity attributable to chemotherapy or 
nivolumab alone or due to scheduling issues, participants can continue on BMS-813160 alone.
•
Participants who need a dose reduction for toxicity attributable to BMS-813160 will continue 
on the reduced dose of BMS-813160 for the remainder of the study. 
•
If a participant needs more than 1 dose reduction of BMS-813160 for toxicity, the participant 
will be taken off BMS-813160 but can continue chemotherapy and/or nivolumab if it is 
determined to be in the participant’s best interest as per the treating investigator and discussed 
with the Medical Monitor.
•
If a participant is off BMS-813160 for more than 28 days, the participant will permanently 
discontinue treatment and be taken off study, unless it is determined to be in the participant’s 
best interest as per the treating investigator and discussed with the Medical Monitor.
BMS-813160 dose modifications are presented in Table 7.4.4-1.
Table 7.4.4-1:
Recommended Dose Modifications for BMS-813160
BMS-813160
BMS-813160
BMS-813160
BMS-813160
Starting Dose
150 mg QD
300 mg QD
300 mg BID
600 mg QD
Dose Reduction 1
150 mg QOD
- Or -
75 mg QD
150 mg QD
150 mg BID
300 mg QD
Abbreviations: BID = twice a day; QD = once daily; QOD = once every other day
7.4.5
FOLFIRI Dose Modifications
Suggested dose modifications for FOLFIRI (5-FU, leucovorin, and irinotecan) are presented in 
Table 7.4.5-1. Recommended dose modifications for irinotecan/5-FU/leucovorin combination 
schedules are provided in Table 7.4.5-2.
Revised Protocol No.: 06
Date: 05-Dec-2019
93
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 7.4.5-1:
Suggested Dose Modifications for FOLFIRI (5-FU, Leucovorin, and 
Irinotecan)
5-FU Bolus
Infusion 5-FU
Irinotecan
Leucovorin
Starting Dose
400 mg/m2
2400 mg/m2
180 mg/m2
400 mg/m2
Dose Reduction 1
320 mg/m2
2000 mg/m2
150 mg/m2
400 mg/m2
Dose Reduction 2
200 mg/m2
1600 mg/m2
90 mg/m2
400 mg/m2
Source: Modified from Table 1 of irinotecan US Package Insert35
Abbreviation: 5-FU = 5-fluorouracil
Table 7.4.5-2:
Recommended Dose Modifications for Irinotecan/5Fluorouracil 
(5FU)/Leucovorin (LV) Combination Schedules
Participants should return to pre-treatment bowel function without requiring antidiarrhea medications for 
at least 24 hours before the next chemotherapy administration. A new cycle of therapy should not begin until 
the granulocyte count has recovered to ≥1500/mm3, and the platelet count has recovered to ≥75,000/mm3, 
and treatment-related diarrhea is fully resolved. Treatment should be delayed 1 to 2 weeks to allow for 
recovery from treatment-related toxicities. If the participant has not recovered after a 2-week delay, 
consideration should be given to dose reduction for the next dose.
Toxicity NCI CTC Gradea (Value)
During a Dose of Therapy
No toxicity 
Maintain dose level 
Neutropenia 
1 (1500 to 1999/mm3)
Maintain dose level 
2 (1000 to 1499/mm3)
↓1 dose level 
3 (500 to 999/mm3)
Omit dose until resolved to ≤Grade 2, then ↓1 dose level
4 (< 500/mm3)
Omit dose until resolved to ≤Grade 2, then ↓2 dose levels
Neutropenic fever
Omit dose until resolved, then ↓2 dose levels
Other hematologic toxicities 
Dose modifications for thrombocytopenia during a cycle of therapy and 
at the start of subsequent cycles of therapy are also based on NCI toxicity 
criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2 - 3 stools/day > pretreatment)
Delay dose until resolved to baseline, then give same dose
2 (4 - 6 stools/day > pretreatment)
Omit dose until resolved to baseline, then ↓1 dose level
3 (7 - 9 stools/day > pretreatment)
Omit dose until resolved to baseline, then ↓1 dose level
4 (≥10 stools/day > pretreatment)
Omit dose until resolved to baseline, then ↓2 dose levels
Other nonhematologic toxicitiesb
1
Maintain dose level
2
Omit dose until resolved to ≤Grade 1, then ↓1 dose level
3
Omit dose until resolved to ≤Grade 2, then ↓1 dose level
4
Omit dose until resolved to ≤Grade 2, then ↓2 dose levels
For mucositis/stomatitis decrease only 5-FU, not irinotecan 
Source: Modified from Table 2 of irinotecan US Package Insert35
a National Cancer Institute Common Toxicity Criteria (version 1.0)
b Excludes alopecia, anorexia, asthenia
Revised Protocol No.: 06
Date: 05-Dec-2019
94
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
7.4.6
Gemcitabine + Nab-Paclitaxel Dose Modifications
Dose modification will be performed according to the nab-paclitaxel (ABRAXANE) package 
insert (Table 7.4.6-1, Table 7.4.6-2, and Table 7.4.6-3).
Table 7.4.6-1:
Dose Level Reductions for Patients with Adenocarcinoma of the 
Pancreas
Dose Level
ABRAXANE (mg/m2)
Gemcitabine
Full Dose
125
1000
1st dose reduction
100
800
2nd dose reduction
75
600
Source: Modified from Table 3 of nab-paclitaxel (ABRAXANE) US Package Insert36
Table 7.4.6-2:
Dose Recommendation and Modifications for Neutropenia and/or 
Thrombocytopenia at the Start of a Cycle or within a Cycle for 
Patients with Adenocarcinoma of the Pancreas
Cycle Day
ANC (cells/mm3)
Platelet Count (cells/mm3)
ABRAXANE / Gemcitabine
Day 1
< 1500
OR
< 100,000
Delay doses until recovery
Day 8
500 to < 1000
OR
50,000 to < 75,000
Reduce 1 dose level
< 500
OR
< 50,000
Withhold doses
Day 15: IF Day 8 doses were reduced or given without modification:
500 to < 1000
OR
50,000 to < 75,000
Reduce 1 dose level from Day 8
< 500
OR
< 50,000
Withhold doses
Day 15: IF Day 8 doses were withheld:
≥1000
OR
≥75,000
Reduce 1 dose level from Day 1
500 to < 1000
OR
50,000 to < 75,000
Reduce 2 dose levels from Day 1
< 500
OR
< 50,000
Withhold doses
Source: Table 4 of nab-paclitaxel (ABRAXANE) US Package Insert36
Abbreviations: ANC = absolute neutrophil count
Revised Protocol No.: 06
Date: 05-Dec-2019
95
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 7.4.6-3:
Dose Modifications for Other Adverse Drug Reactions in Patients 
with Adenocarcinoma of the Pancreas
Adverse Drug Reaction
ABRAXANE
Gemcitabine
Febrile Neutropenia:
Grade 3 or 4
Withhold until fever resolves and ANC ≥1500; resume at next lower dose level
Peripheral Neuropathy:
Grade 3 or 4
Withhold until improves to ≤Grade 1;
resume at next lower dose level
No dose reduction
Cutaneous Toxicity:
Grade 2 or 3
Reduce to next lower dose level; discontinue treatment if toxicity persists
Gastrointestinal Toxicity:
Grade 3 mucositis or diarrhea
Withhold until improves to ≤Grade 1; resume at next lower dose level
Source: Table 5 of nab-paclitaxel (ABRAXANE) US Package Insert36
Since FOLFIRI and Gem/nab-paclitaxel are standard therapies for CRC and pancreatic cancers, 
sites may use their discretion for dosing these regimens based on a participant’s tolerability. Any 
laboratory only abnormalities without clinical manifestations or electrolyte abnormalities that may 
be managed with supplementation also do not automatically need dose modification.
7.4.7
Nivolumab Dose Modifications
No dose modifications are allowed. 
Participants should be carefully monitored for infusion reactions during nivolumab administration. 
If an acute infusion reaction is noted, participants should be managed according to Section 7.4.7.4.
Doses of nivolumab may be interrupted, delayed, or discontinued depending on how well the 
participant tolerates the treatment. Dosing visits are not skipped, only delayed.
7.4.7.1
Dose Delays in Nivolumab (Cohort 3b of Arm B and All Cohorts of 
Arm C)
Participants who experience the following must have all study treatment(s) delayed:
•
Grade 2 non-skin, nivolumab-related AE, with the exception of fatigue, nausea, vomiting, and 
anemia.
•
Grade 2 drug-related creatinine, AST, ALT, and/or total bilirubin abnormalities.
•
Grade 3 skin, drug-related AE.
•
Grade 3 drug-related fatigue, nausea, vomiting, and anemia.
•
Grade 3 drug-related laboratory abnormality, with the following exceptions:
−
Grade 3 lymphopenia or asymptomatic amylase or lipase elevations do not require dose 
delay.
−
Grade > 3 AST, ALT, total bilirubin will require dose discontinuation (see Section 8.1).
•
Any AE, laboratory abnormality, or intercurrent illness, which in the judgment of the 
investigator, warrants delaying the dose of study medication.
Revised Protocol No.: 06
Date: 05-Dec-2019
96
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Criteria for participants who are required to permanently discontinue study treatments are listed in 
Section 7.4.7.3. Participants not meeting guidelines for permanent discontinuation will be 
permitted to resume therapy based on the criteria specified below in Section 7.4.7.2. Participants 
eligible to resume study therapy will resume study therapy at the next scheduled treatment visit 
following their last received study medication dose.
7.4.7.2
Criteria to Resume Treatment in Nivolumab (Arm C and Cohort 3b)
Participants experiencing AEs not meeting criteria for permanent discontinuation as outlined 
in Section 7.4.7.3 may resume treatment with study treatment under the following criteria:
1) Participants may resume treatment with study treatment when the drug-related AE(s) resolve 
to Grade ≤1 or baseline value with the following EXCEPTIONS:
a) Participants may resume treatment in the presence of Grade 2 fatigue.
b) Participants who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity.
2) Grade 2 eye pain or blurred vision not meeting DLT criteria (Section 7.4.1) must resolve to 
baseline prior to resuming study treatment.
3) Drug-related pulmonary toxicity, diarrhea, or colitis must have resolved to baseline before 
treatment is resumed.
4) Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment.
5) If the criteria to resume treatment are met, the participant should restart treatment at the next 
scheduled time point per protocol.
6) The consideration to re-initiate study treatment under these exceptions will be made on a case-
by-case basis after considering the overall benefit/risk profile and in consultation between the 
investigator and the BMS Medical Monitor. Any AE with clinical risk will be assessed on a 
case-by-case basis with the investigator and the BMS Medical Monitor to determine the risks 
and benefits of continuing therapy following resolution vs discontinuing therapy permanently. 
7) If treatment with study treatment is delayed > 6 weeks, the participant must be permanently 
discontinued from study treatment, except as specified in Section 7.4.1. 
7.4.7.3
Guidelines for Permanent Discontinuation in Nivolumab (Arm C and 
Cohort 3b)
Participants will be required to permanently discontinue nivolumab for the following AEs:
1) Clinical deterioration, as assessed by the investigator.
2) Grade 3 infusion reaction that does not return to Grade 1 in less than 6 hours.
3) Grade 3 pneumonitis.
4) Life-threatening skin toxicity (toxic epidermal necrolysis).
5) Grade 3 uveitis.
6) Grade 3 myocarditis.
7) Any Grade 4 AE; however, an exception may be made for the following upon consultation 
between the investigator and BMS Medical Monitor:
Revised Protocol No.: 06
Date: 05-Dec-2019
97
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
a) Grade 4 electrolyte abnormalities < 72 hours in duration.
b) Grade 4 neutropenia < 5 days in duration.
c) Grade 4 lymphopenia.
d) Grade 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis.
8) Abnormal liver function tests meeting criteria for a potential DILI.
9) Any dosing delay lasting > 6 weeks will be cause for permanent discontinuation. Extensions 
to the period of dose delays may be granted for individual participants on a case-by-case basis 
after specific consultation and agreement between the investigator and BMS Medical Monitor 
in settings where benefit/risk may justify continued study treatment (eg, participant deriving 
clinical benefit who requires prolonged steroid taper for management of non-DLT 
immune-related AEs or experiences delays for management of a non-drug-related AE).
a) Accordingly, dosing delays to allow for prolonged steroid tapers to manage drug-related 
AEs are allowed. Additionally, dosing delays > 6 weeks that occur for non-drug-related 
reasons may be allowed if approved by the BMS Medical Monitor.
b) Prior to re-initiating treatment in a participant with a dosing delay lasting > 6 weeks, the 
BMS Medical Monitor must be consulted.
c) Tumor assessments should continue as per protocol even if dosing is delayed.
All participants who discontinue study treatment should comply with protocol-specified follow-up 
procedures as outlined in Table 2-7. The only exception to this requirement is when a participant
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (eg, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page.
7.4.7.4
Treatment of Treatment-related Infusion Reactions
Nivolumab and the combination therapies may induce infusion or hypersensitivity reactions. If
such a reaction were to occur, it may manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgia, hypo- or hypertension, bronchospasm, or other symptoms.
Infusion reactions should be graded according to CTCAE v4.03 guidelines. Any Grade 3 or 
Grade 4 infusion reaction should be reported within 24 hours to the Sponsor’s Medical Monitor or 
designee, and reported as an SAE if it meets the criteria.
It may be unclear if an infusion reaction is due to the combination therapy, nivolumab, or to both. 
Therefore, 1 set of treatment recommendations (based on the most conservative treatments for 
infusion reactions due to either study treatment) is provided below and may be modified based on 
clinical judgment, local treatment standards and guidelines, and/or specific symptoms, as 
appropriate:
Revised Protocol No.: 06
Date: 05-Dec-2019
98
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
For Grade 1 symptoms: Mild reaction (eg, localized cutaneous reactions including mild pruritus, 
flushing, rash), requires infusion rate to be decreased; intervention may be indicated.
•
Decrease the rate of the study treatment infusion until recovery from symptoms.
•
Remain at bedside and monitor the participant’s vital signs until resolution of symptoms. 
Diphenhydramine 50 mg may be administered at the discretion of the treating physician.
•
When symptoms resolve, restart the infusion at the original infusion rate.
•
If a participant has an infusion reaction with nivolumab, combination therapy can be given 
(without prophylactic medications) if the infusion reaction resolves within 3 hours. For 
scheduling purposes, infusion may be given the next day. Prophylactic pre-infusion 
medications should be given prior to all subsequent nivolumab infusions.
•
If a participant has an infusion reaction, prophylactic pre-infusion medications should be given 
prior to all subsequent infusions.
•
The following prophylactic pre-infusion medications are recommended prior to future 
infusions: diphenhydramine 50 mg (or equivalent) and/or paracetamol (acetaminophen) 325 to 
1,000 mg at least 30 minutes before additional study treatment administrations.
For Grade 2 symptoms: Moderate reaction (ie, any symptom not listed above [mild symptoms] 
or below [severe symptoms] such as generalized pruritus, flushing, rash, dyspnea, and hypotension 
with systolic blood pressure [BP] > 80 mm Hg), requires infusion interruption but responds 
promptly to symptomatic treatment (eg, antihistamines, nonsteroidal anti-inflammatory drugs, 
narcotics, corticosteroids, IV fluids); prophylactic pre-infusion medications indicated for 
≤24 hours.
•
Interrupt the study treatment infusion.
•
Begin an IV infusion of normal saline, and treat the participant with diphenhydramine 50 mg 
IV (or equivalent) and/or paracetamol (acetaminophen) 325 to 1,000 mg.
•
Remain at bedside and monitor the participant’s vital signs until resolution of symptoms. 
Corticosteroid therapy may be administered at the discretion of the treating physician.
•
When symptoms resolve, restart the infusion at 50% of the original infusion rate; if no further 
complications ensue after 30 minutes, the rate may be increased to 100% of the original 
infusion rate.
•
Monitor the participant closely. If symptoms recur, immediately discontinue the infusion; no 
further study treatment will be administered at that visit. Administer diphenhydramine 50 mg 
IV, and remain at bedside and monitor the participant until resolution of symptoms.
•
If a participant has an infusion reaction with nivolumab infusion, combination therapy infusion 
can be given (without prophylactic medications) if the infusion reaction resolves within 
3 hours. For scheduling purposes, the combination therapy infusion may be given the next day. 
Prophylactic pre-infusion medications should be given prior to all subsequent nivolumab 
infusions.
•
If a participant has an infusion reaction with a combination therapy, prophylactic pre-infusion 
medications should be given prior to all subsequent infusions.
Revised Protocol No.: 06
Date: 05-Dec-2019
99
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
The following prophylactic pre-infusion medications are recommended prior to future 
infusions: diphenhydramine 50 mg (or equivalent) and/or paracetamol (acetaminophen) 325 to 
1,000 mg should be administered at least 30 minutes before additional study treatment 
administrations. If necessary, corticosteroids (up to 25 mg of SOLU-CORTEF® or equivalent) 
may be used.
•
The amount of study treatment infused must be recorded.
For Grade 3 or Grade 4 symptoms: Severe reaction such as bronchospasm, generalized urticaria, 
systolic BP < 80 mm Hg, or angioedema; Grade 3 symptoms including prolonged symptoms, 
which require 6 or more hours to respond to symptomatic medication and/or discontinuation of 
infusion; recurrence of symptoms following initial improvement; hospitalization indicated for 
other clinical sequelae, such as renal impairment, pulmonary infiltrates; Grade 4: life-threatening; 
pressor or ventilation support indicated.
•
Immediately discontinue the study treatment infusion. No further study treatment will be 
administered. The amount of study treatment infused must be recorded on the CRF.
•
Begin an IV infusion of normal saline, and treat the participant as follows: Recommend 
bronchodilators, epinephrine 0.2 to 1.0 mg of a 1:1,000 solution for subcutaneous (SC) 
administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly for IV administration, 
and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV (or equivalent), as 
needed.
•
Remain at bedside and monitor the participant’s vital signs until recovery from symptoms.
•
The participant should be monitored until the Investigator is comfortable that the symptoms 
will not recur.
•
Investigators should follow their institutional guidelines for the treatment of anaphylaxis.
In the case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or 
generalized pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine, or corticosteroids).
7.4.8
Treatment Beyond Progression (Arm C only)
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of PD.37
Participants will be permitted to continue treatment beyond initial RECIST v1.1 defined PD, 
assessed by the investigator, as long as they meet the following criteria:
•
Investigator-assessed clinical benefit
•
Tolerance of study treatment
•
Stable performance status
•
Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases)
Revised Protocol No.: 06
Date: 05-Dec-2019
100
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Participant provides written informed consent prior to receiving additional treatment. All other 
elements of the main consent including description of reasonably foreseeable risks or 
discomforts, or other alternative treatment options will still apply.
A radiographic assessment/scan should be performed at the next scheduled scan to determine 
whether there has been a decrease in the tumor size or continued PD. The assessment of clinical 
benefit should be balanced by clinical judgment as to whether the participant is clinically 
deteriorating and unlikely to receive any benefit from continued study treatment.
If the investigator feels that the participant continues to achieve clinical benefit by continuing 
treatment, the participant should remain on the trial and continue to receive monitoring according 
to the Time and Events Schedule (Section 2).
For the participants who continue study therapy beyond progression, further progression is defined 
as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time 
of initial PD. This includes an increase in the sum of diameters of all target lesions and/ or the 
diameters of new measurable lesions compared to the time of initial PD. Study treatment should 
be discontinued permanently upon documentation of further progression. The tumor burden 
volume from time of initial progression should be used as the reference baseline for comparison 
with the post progression assessment.
New lesions are considered measureable at the time of initial progression if the longest diameter 
is at least 10 mm (except for pathological lymph nodes which must have a short axis of at least
15 mm). Any new lesion considered non-measureable at the time of initial progression may 
become measureable and therefore included in the tumor burden if the longest diameter increases 
to at least 10 mm (except for pathological lymph nodes which must have a short axis of at least 
15 mm). In situations where the relative increase in total tumor burden by 10% is solely due to 
inclusion of new lesions which become measurable, these new lesions must demonstrate an 
absolute increase of at least 5 mm.
7.5
Preparation/Handling/Storage/Accountability
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study Participants. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment
should not be dispensed and contact BMS immediately.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure treatment is accurately administered. This includes 
documentation of treatment storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Revised Protocol No.: 06
Date: 05-Dec-2019
101
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
For study treatments not provided by BMS and obtained commercially by the site, storage should 
be in accordance with the product label.
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
•
Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 2 and as specified by the protocol team (eg, Study Reference Manual).
7.6
Treatment Compliance
Study treatment compliance, including infusions administered in the clinical facility by trained 
medical personnel, will be periodically monitored by treatment accountability and review of 
dosing diary cards. Treatment accountability should be reviewed by the site study staff at each 
visit to confirm treatment compliance. Sites should discuss discrepancies with the participant at 
each on-treatment study visit. 
7.7
Concomitant Therapy
7.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to study treatment administration in the study 
are described below. Medications taken within 4 weeks prior to study treatment administration 
must be recorded on the CRF.
In limited circumstances (eg, life threatening illness) the use of the below medications may be 
permitted. The investigator should contact and confirm agreement with the BMS Medical Monitor 
(and acknowledgement from the contract research organization medical monitor, if any) prior to 
the administration of any concomitant medications which are restricted or prohibited.
7.7.1.1
Prohibited Treatments
•
In vitro, the metabolism of BMS-813160 was primarily mediated via CYP3A4, with some 
contribution from CYP3A5, and BMS-813160 was also a substrate for P-glycoprotein (P-gp). 
Based on these results, the potential exists for DDI if BMS-813160 is co-administered with 
inhibitors or inducers of CYP3A or P-gp. Therefore use of any strong inhibitors or inducers of 
CYP3A4 or P-gp is not allowed (see Appendix 8).
•
Grapefruit and Seville oranges and their juices can inhibit CYP3A4 and must not be consumed 
while on study. 
•
MATE inhibitors for the first 2 weeks of BMS-813160 monotherapy (Part 1). (See Appendix 
9)
•
Concomitant use of strong inhibitors of UGT1A1 in FOLFIRI arm. (See Appendix 10)
•
Exposure to any investigational drug or placebo within 4 weeks of study treatment
administration. 
•
Class IA antiarrhythmics (eg, quinidine, procainamide, dysopiramide)
•
Class IC antiarrhythmics (eg, flecainide, propafenone, moricizine)
•
Tricyclic antidepressants
Revised Protocol No.: 06
Date: 05-Dec-2019
102
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Any live / attenuated vaccine (eg, varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella [MMR]) during treatment and until 100 days post last dose.
7.7.1.2
Restricted Treatments
•
Caution is warranted with concomitant use of BMS-813160 and:
−
MATE1 substrates with a narrow therapeutic index (see Appendix 11).
−
Moderate inhibitors or inducers of CYP3A4. Moderate CYP3A4 modulators (ie, inhibitor 
or inducer) are allowed with caution only after the first 7 weeks. See Appendix 8 for a list 
of CYP3A4 modulators. 
−
Class IB antiarrhythmic drugs (eg, lidocaine, tocainide, mexilitine) due to potential sodium 
channel blockade
−
Methadone (in particular at high doses) due to potential sodium channel blockade
7.7.2
Other Restrictions and Precautions
•
Caution should be used for participants with renal or hepatic impairment in 
Gemcitabine/nab-paclitaxel, or FOLFIRI arms.
7.7.2.1
Imaging Restriction and Precautions
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history and renal status), the appropriate imaging modality and 
contrast regimen for each participant. Imaging contraindications and contrast risks should be 
considered in this assessment. Participants with renal insufficiency should be assessed as to 
whether or not they should receive contrast and if so, what type and dose of contrast is appropriate. 
Specific to magnetic resonance imaging (MRI), participants with severe renal insufficiency 
(ie, estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) are at increased risk of 
nephrogenic systemic fibrosis. Magnetic resonance imaging contrast should not be given to this 
participant population. In addition, participants are excluded from MRI if they have tattoos, 
metallic implants, pacemakers, etc.
The ultimate decision to perform MRI in an individual participant in this study rests with the site 
radiologist, the investigator and the standard set by the local Ethics Committee.
7.7.3
Permitted Therapy
•
Inhaled or intranasal corticosteroids (with minimal systemic absorption may be continued if 
the participant is on a stable dose) and adrenal replacement steroid doses of prednisone 
> 10 mg daily or equivalent are permitted in the absence of active autoimmune disease. Non
absorbed intra-articular steroid injections will be permitted.
•
Immunosuppressive agents and the use of systemic corticosteroids are permitted in the context 
of treating AEs. Corticosteroids are allowed for prophylaxis in the chemotherapy arms if 
clinically indicated as part of standard of care. Participants receiving corticosteroids must be 
Revised Protocol No.: 06
Date: 05-Dec-2019
103
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
at prednisone < 10 mg daily or equivalent prior to re-initiation of study treatment. Participants 
may continue to receive hormone replacement treatment.
•
The inactivated seasonal influenza vaccine can be given to participants while on treatment 
without restriction. Influenza vaccines containing live virus or other clinically indicated 
vaccinations for infectious diseases (ie, PNEUMOVAX®, varicella vaccine, etc) may be 
permitted but must be discussed with the BMS Medical Monitor (or designee) and may require 
a study treatment washout period prior to and after administration of the vaccine.
7.7.4
Palliative Local Therapy
Palliative and supportive care for disease-related symptoms may be offered to all participants on 
the study. Limited radiation treatment or surgery to control isolated lesions is permitted for 
participants following consultation with the BMS Medical Monitor (or designee).
Participants should not receive study treatment during radiation because the potential for 
overlapping toxicities with radiotherapy and study treatment is not known. If palliative 
radiotherapy in short courses and for isolated fields is required to control symptoms not clearly 
related to disease progression, then study treatment administration should be withheld, if possible, 
for at least 1 week before radiation and for at least 1 week after its completion.
Participants should be closely monitored for any potential toxicity during and after receiving 
radiotherapy. Prior to resuming study treatment, radiotherapy-related AEs should resolve to 
Grade ≤1 or baseline, and participants must meet relevant eligibility criteria as determined by the 
BMS Medical Monitor (or designee) in discussion with the investigator. The BMS Medical 
Monitor (or designee) must be consulted prior to re-initiating study treatment in a participant with 
a dosing delay lasting > 8 weeks from the previous dose.
Details of palliative radiotherapy should be documented in the source records and CRF. Details in 
the source records should include dates of treatment, anatomic site, dose administered and 
fractionation schedule, and AEs. Symptoms requiring palliative radiotherapy should be evaluated 
for objective evidence of disease progression. Participants receiving palliative radiation of target 
lesions will have the evaluation of ORR just prior to radiotherapy, but these participants will no 
longer be evaluable for the determination of response subsequent to the date palliative radiation 
occurs.
For participants who need to undergo surgery during the study, it is recommended to hold study 
treatment(s) for at least 2 weeks before (if elective) and 2 weeks after surgery, or until the 
participant recovers from the procedure, whichever is longer. Prior to resuming study treatment, 
surgically related AEs should resolve to Grade 1 or baseline, and participants must meet relevant 
eligibility criteria as determined by the BMS Medical Monitor (or designee) in discussion with the 
investigator. The BMS Medical Monitor (or designee) must be consulted prior to re-initiating study 
treatment in a participant with a dosing delay lasting > 8 weeks from the previous dose.
Revised Protocol No.: 06
Date: 05-Dec-2019
104
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
7.8
Treatment After the End of the Study
At the end of the study or study part, BMS will not continue to provide BMS supplied study 
treatment to participants/investigators unless BMS chooses to extend the study. The investigator 
should ensure that the participant receives appropriate standard of care to treat the condition under 
study.
Revised Protocol No.: 06
Date: 05-Dec-2019
105
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Participants MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:
•
Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information.
•
Any clinical AE, laboratory abnormality or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant.
•
Termination of the study by the BMS.
•
Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: under 
certain specific circumstances, and only in countries where local regulations permit, a 
participant who has been imprisoned may be permitted to continue as a participant. Strict 
conditions apply and BMS approval is required.)
•
Progression of Disease except as described in Section 7.4.8.
•
Pregnancy
In the case of pregnancy, the investigator must immediately notify within 24 hours of awareness 
of the pregnancy, the BMS Medical Monitor/designee of this event. In most cases, the study 
treatment will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for participant safety). Refer to Section 9.2.5, Pregnancy.
All participants who discontinue study treatment should comply with protocol specified follow-up 
procedures as outlined in Section 2. The only exception to this requirement is when a participant
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page.
8.1.1
Post Study Treatment Study Follow-up
In this study, safety is a key endpoint of the study. Post study follow-up is of critical importance 
and is essential to preserving participant safety and the integrity of the study. Participants who 
discontinue study treatment must continue to be followed for collection of outcome and/or survival 
follow-up data as required and in line with Section 5 and Table 2-7 until death, 30 days (Arm A, 
Revised Protocol No.: 06
Date: 05-Dec-2019
106
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Cohorts 3a and 3c [Arm B; Part 2], and Arm D) and 100 days (Arm C and Cohort 3b [Arm B, Part 
2]) post EOT, or the conclusion of the study.
8.2
Discontinuation from the Study
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 
•
Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.
•
The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page.
•
In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.
•
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-Up
•
All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.
•
Lost to follow-up is defined by the inability to reach the participant after a minimum of three
documented phone calls, faxes, or emails as well as lack of response by participant to 1
registered mail letter. All attempts should be documented in the participant’s medical records.
•
If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.
•
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the participant’s informed consent, then the investigator may use a 
Sponsor retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 
•
The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.
•
If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the participant’s medical 
records.
Revised Protocol No.: 06
Date: 05-Dec-2019
107
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
8.4
Study Termination
The use of a 2-stage design allows for possible early termination of enrollment into an expansion 
cohort based on anti-tumor activity evaluation of Stage I patients. While there is no formal stopping 
rule based on efficacy, a futility signal based on Sponsor’s assessment may also lead to cohort 
termination.
BMS continuously evaluates the benefit/risk of the program and may choose to hold further 
recruitment in a particular cohort or at a particular site, or terminate the development of 
BMS-813160 for reasons including, but not limited to, safety and efficacy.
Revised Protocol No.: 06
Date: 05-Dec-2019
108
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
9
STUDY ASSESSMENTS AND PROCEDURES
•
Study procedures and timing are summarized in the Schedule of Activities. 
•
Protocol waivers or exemptions are not allowed.
•
All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment.
•
Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct.
•
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before treatment. The investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.
•
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the Schedule of Activities.
9.1
Efficacy Assessments
Tumor assessments at other time points may be performed if clinically indicated, and should be 
submitted to the central imaging vendor as soon as possible. Unscheduled CT/MRI should be 
submitted to central imaging vendor. X-rays and bone scans that clearly demonstrate interval
progression of disease, for example most commonly as unequivocal lesions that are unmistakably 
new since the prior CT/MRI, should be submitted to central imaging vendor. Otherwise, X-rays 
and bone scans do not need to be submitted centrally.
Disease assessment with computed tomography (CT) and/or MRI, as appropriate, will be 
performed at baseline and approximately every 8 weeks (± 1 week from Cycle 1 Day 1) until 
disease progression, treatment discontinuation, withdrawal from study, or start of subsequent 
treatment, whichever is earlier.
A best overall response of SD requires a minimum of 49 days on study from date of first dose to 
the date of the first imaging assessment.
9.1.1
Imaging Assessment for the Study
All radiologic images will be submitted to a centralized imaging core lab for storage and potential 
future blinded independent central review (BICR) per Sponsor request. Sites should be trained 
prior to scanning the first study participant. Image acquisition guidelines and submission process 
will be outlined in the CV202103 Imaging Manual to be provided by the core lab.
Tumor assessment with contrast-enhanced CT scans acquired on dedicated CT equipment is 
preferred for this study. Contrast-enhanced CT of the chest, abdomen, pelvis, and other 
known/suspected sites of disease should be performed for tumor assessments. Should a participant 
have contraindication for CT intravenous contrast, a non-contrast CT of the chest and a 
Revised Protocol No.: 06
Date: 05-Dec-2019
109
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
contrast-enhanced MRI of the abdomen, pelvis, and other known/suspected sites of disease should 
be obtained.
Should a participant have contraindication for both MRI and CT intravenous contrasts, a 
non-contrast CT of the chest and a non-contrast MRI of the abdomen, pelvis, and other 
known/suspected sites of disease should be obtained.
Should a participant have contraindication for MRI (eg, incompatible pacemaker) in addition to 
contraindication to CT intravenous contrast, a non-contrast CT of the chest, abdomen, pelvis, and 
other known/suspected sites of disease is acceptable.
CT and MRI scans should be acquired with slice thickness of 5 mm or less with no intervening 
gap (contiguous). Every attempt should be made to image each participant using an identical 
acquisition protocol for all imaging time points. 
Use of CT component of a positron emission tomography (PET)-CT scanner: Combined modality 
scanning such as with fluorodeoxyglucose (FDG) PET-CT is increasingly used in clinical care, 
and is a modality/technology that is in rapid evolution; therefore, the recommendations outlined 
here may change rather quickly with time. At present, low dose or attenuation correction CT 
portions of a combined FDG PET-CT are of limited use in anatomically-based efficacy 
assessments and it is therefore suggested that they should not be substituted for dedicated 
diagnostic contrast enhanced CT scans for anatomically-based RECIST v1.1 measurements. 
However, if a site can document that the CT performed as part of a FDG PET-CT is of identical 
diagnostic quality to a diagnostic CT (with IV and oral contrast) then the CT portion of the FDG 
PET-CT can be used for RECIST v1.1 measurements. Note, however, that the FDG PET portion 
of the CT introduces additional data which may bias an investigator if it is not routinely or serially 
performed.
Participants with symptoms or history of brain metastasis should have a MRI of the brain without 
and with contrast. CT of the brain without and with contrast can be performed if MRI is 
contraindicated (see Table 2-1).
Bone scans should be performed if clinically indicated. 
Assessments will be performed at baseline and at the time points described per RECIST v1.1 
criteria (see Appendix 5), until disease progression per RECIST v1.1 criteria, or withdrawal from 
the study.
9.2
Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. 
Revised Protocol No.: 06
Date: 05-Dec-2019
110
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Contacts for SAE reporting are specified in Appendix 3.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
Sections 5.6.1 and 5.6.2 in the BMS-813160 IB27 represent the Reference Safety Information to 
determine expectedness of SAEs for expedited reporting. 
All SAEs must be collected from the time of signing the consent, including those thought to be 
associated with protocol-specified procedures and within 30 days (Arms A, B [Cohorts 3a and 3c], 
and D) and 100 days (Arm C and Cohort 3b [Arm B, Part 2]) of discontinuation of dosing.
All nonserious AEs must be collected at the start of study treatment until the time points specified 
in the Schedule of Activities (Section 2).
•
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the CRF module.
•
All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 
•
The investigator will submit any updated SAE data to the Sponsor within 24 hours of updated 
information being available.
The method of evaluating, and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
9.2.2
Method of Detecting AEs and SAEs
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a participant. Care should be taken not to introduce bias when 
collecting AE and/or SAEs. Inquiry about specific AEs should be guided by clinical judgment in 
the context of known AEs, when appropriate for the program or protocol.
9.2.3
Follow-up of AEs and SAEs
•
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).
•
Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment as appropriate.
•
 All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in 
Section 9.2 will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in Appendix 3.
Revised Protocol No.: 06
Date: 05-Dec-2019
111
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
9.2.4
Regulatory Reporting Requirements for SAEs
•
Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met.
•
An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the institutional review board (IRB)/ independent 
ethics committee (IEC), if appropriate according to local requirements.
Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC and FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320. A SUSAR (suspected, unexpected serious adverse 
reaction) is a subset of SAEs and will be reported to the appropriate regulatory authorities and 
investigators following local and global guidelines and requirements.
9.2.5
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
10 months after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to BMS Designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in Appendix 3
If the investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, or reinitiation of study treatment, a discussion between the investigator and the 
BMS Medical Monitor/designee must occur. 
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designee. In order for Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.
•
Any laboratory test result that is clinically significant or meets the definition of an SAE 
Revised Protocol No.: 06
Date: 05-Dec-2019
112
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Any laboratory test result abnormality that required the participant to have study treatment
discontinued or interrupted
•
Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia vs low hemoglobin value).
9.2.7
Potential Drug Induced Liver Injury (DILI)
Specific criteria for identifying potential DILI have not been identified for this protocol. Standard 
medical practice in identifying and monitoring hepatic issues should be followed.
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and Appendix 3 for reporting 
details).
Potential drug induced liver injury is defined as: 
•
Amino transferase (ALT or AST) elevation > 3 times ULN
•
AND
•
Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
•
AND
•
No other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic.
9.2.8
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, electrocardiogram, 
x-ray filming, any other potential safety assessment required or not required by protocol should 
also be recorded as a nonserious or serious AE, as appropriate, and reported accordingly.
9.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. Overdoses that meet the regulatory 
definition of SAE will be reported as an SAE (see Appendix 3).
For this study, any dose of 10% greater than the daily dose within a 24-hour time period (± 8 hours) 
will be considered an overdose. In the event of an overdose the investigator/treating physician
should:
•
Contact the Medical Monitor immediately
Revised Protocol No.: 06
Date: 05-Dec-2019
113
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Closely monitor the participant for AEs/SAEs and laboratory abnormalities until effects can 
no longer be detected systemically 
•
Obtain a plasma sample for PK analysis if requested by the Medical Monitor (determined on a 
case-by-case basis)
•
Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
9.4
Safety
Planned time points for all safety assessments are listed in the Schedule of Activities.
9.4.1
Physical Examinations
Refer to Schedule of Activities.
9.4.2
Vital Signs
Refer to Schedule of Activities.
9.4.3
Electrocardiograms
Refer to Schedule of Activities. ECGs will be evaluated by the investigator for any clinically 
significant changes or for changes meeting dose modifying criteria. In addition ECGs will be sent 
to the Sponsor for central read.
9.4.4
Clinical Safety Laboratory Assessments
•
Investigators must document their review of each laboratory safety report.
•
Results of clinical laboratory tests performed during the screening period must be available 
prior to dosing. All laboratory tests (except for pregnancy testing) may be performed up to 
3 days prior to dosing, and the results MUST be reviewed prior to dosing. Pregnancy testing 
must be done within 24 hours prior to dosing
.
Revised Protocol No.: 06
Date: 05-Dec-2019
114
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Blood Urea Nitrogen (BUN)
Uric acid
Lipase
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Amylase
Thyroid Panel (Includes TSH, Free T3 and Free T4)
Urinalysis (screening and cross-over baseline only)
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive 
on the dipstick
Serology (screening and cross-over baseline only)
Serum for hepatitis C antibody, hepatitis B surface antigen, HIV-1 and -2 antibody (as 
mandated by local requirement)
Pregnancy test (WOCBP only) [Serum or urine pregnancy test must be performed within 
24 hours prior to administration of study treatment and on Day 1 of each cycle regardless of 
dosing schedule.]
Follicle stimulating hormone (FSH) [Screening only; only women not considered WOCBP. 
Refer to Appendix 4 for definitions and guidelines.]
9.4.5
Imaging Safety Assessment
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment. 
Revised Protocol No.: 06
Date: 05-Dec-2019
115
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
9.5
Pharmacokinetics
9.5.1
Pharmacokinetic Assessment of BMS-813160 following BMS-813160 
Monotherapy
Pharmacokinetics of BMS-813160 and its metabolite (BMS-939429) will be derived from plasma 
concentration vs time and urinary excretion data. Individual participant PK parameter values will 
be derived by noncompartmental methods by a validated PK analysis program. Actual times will 
be used for the analyses.
The PK parameters to be assessed for BMS-813160 following multiple dose administration in 
monotherapy phase include but not limited to the following:
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-24)
Area under the concentration-time curve from time 0 to 24 hours post 
dose
AUC(0-8)
Area under the concentration-time curve from time 0 to 8 hours post 
dose
C24
Observed plasma concentration at 24 hours post dose (QD dosing only)
Ctrough
Trough observed plasma concentration
CLT/F
Apparent total body clearance
AI
Accumulation index, calculated based on ratio of AUC(0-24) and Cmax 
at steady state to after the first dose
%UR
Percent urinary recovery over dosing interval
CLR
Renal clearance
In addition, the following PK parameters for BMS-813160 metabolite (BMS-939429) may also be 
assessed after multiple dose administrations, if data permit:
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-24)
Area under the plasma concentration-time curve from time zero to 
24 hours post dose
AUC(0-8)
Area under the concentration-time curve from time 0 to 8 hours post dose
C24
Observed plasma concentration at 24 hours post dose
Ctrough
Trough observed plasma concentration
Revised Protocol No.: 06
Date: 05-Dec-2019
116
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
AI
Accumulation index, calculated based on ratio of AUC(0-24) and Cmax 
at steady state to after the first dose
%UR
Percent urinary recovery over 24 hours corrected for molecular weight
CLR
Renal clearance
MR_Cmax
Ratio of metabolite Cmax to parent Cmax, corrected for molecular 
weight
MR_AUC(0-24)
Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for 
molecular weight
Individual participant PK parameter values will be derived by non-compartmental methods by a 
validated PK analysis program. Actual times will be used for the analyses.
Table 9.5.1-1 lists the blood and urine sampling schedule to be followed for the assessment of PK
of BMS-813160, the BMS-813160 metabolite (BMS-939429), and MATE-renal transporter 
biomarkers. Further details of blood and urine collection and processing will be provided to the 
site in the laboratory procedure manual.
Revised Protocol No.: 06
Date: 05-Dec-2019
117
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.5.1-1:
Pharmacokinetic Sampling Schedule for BMS-813160 in 2-week 
Monotherapy in Part 1 (Arms A, B, and C)
Sample Collection Time
Study
Cyclea / Day
Time (Event)
Time
(Relative to Dosing)
Hour: Minb
PK
Plasma Samplec
MATE-renal
Transporter
Plasma Sampled
PK/MATE-renal
Transporter
Urine Samplec,d
Cycle 0
Day -1
0 h
-24:00
X
X
(0 h - 8 h cumulative)
8 h
-16:00
X
-16:00 to 00:00
Xe
(8 h - 24 h
cumulative for 
MATE)
X
(pre-dose urine 
sample for PK)
Cycle 0
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
X
00:30
X
X
(0 h - 8 h cumulative)
1:00
X
2:00
X
X
3:00
X
4:00
X
X
6:00
X
X
8:00
X
X
8:00 to 24:00
X
(8 h - 24 h 
cumulative)
Cycle 0
Day 2
0 h (pre-dose)
00:00f
X
X
Cycle 0
Day 3
0 h (pre-dose)
00:00f
X
Cycle 0
Day 7
0 h (pre-dose)
00:00f
X
Cycle 0
Day 14
0 h (pre-dose)
00:00f
X
X
X
(0 h - 8 h cumulative)
00:30
X
1:00
X
2:00
X
X
3:00
X
4:00
X
X
6:00
X
X
8:00
X
X
8:00 to 24:00
X
(8 h - 24 h 
cumulative)
Cycle 1
Day 1
0 h
00:00f
X
a 1 cycle = 4 weeks, except for Cycle 0 (2 weeks).
b The following windows serve as a guideline for PK sample collections and will be considered within window:
   •  ± 2 minutes for samples within the first 4 hours after dose.
   •  ± 15 minutes for samples after the first 4 hours through 24 hours after dose.
   •  ± 1 h for the remaining time points following 24 hours after dose.
c For the measurement of BMS-813160 and the metabolite BMS-939429 (M1). Apply to both BID and QD regimens 
in all combination arms.
Revised Protocol No.: 06
Date: 05-Dec-2019
118
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
d For the measurement of NMN and creatinine (MATE1/renal transporter biomarkers).
e Pre-dose urine concentration will be measured from 8 - 24 h pre-dose urine sample collected on Day -1. Total urine 
volume will be documented for 0 - 8 h and 8 - 24 h.
f Sample collected 12 h (BID regimen) or 24 h (QD regimen) after the previous dose (trough sample) and prior to 
the dose on that day.
9.5.2
Pharmacokinetic Assessment of BMS-813160 during Chemotherapy
Combination Treatment in Part 1 (Arms A and B)
Plasma samples for BMS-813160 and metabolite BMS-939429 (M1) will be collected for all 
participants receiving the chemotherapy combination treatments (Arms A and B [Part 1]). In 
addition, following non-compartmental PK parameters will be reported, for BMS-813160 and 
BMS-939429 where data permit.
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-24)
Area under the concentration-time curve from 0 to 24 hours post dose
AUC(0-8)
Area under the concentration-time curve from time 0 to 8 hours post dose
C24
Observed plasma concentration 24 hours post dose (QD dosing only)
Ctrough
Trough observed plasma concentration
Table 9.5.2-1 lists the blood sampling schedule to be followed for the assessment of PK of 
BMS-813160 following the chemotherapy combination treatment (Arms A and B) in Part 1. 
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
Revised Protocol No.: 06
Date: 05-Dec-2019
119
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.5.2-1:
Pharmacokinetic Sampling Schedule for BMS-813160 during 
Chemotherapy Combination Treatment in Part 1 (Arms A and B)
Sample Collection Time
Time
Study
Cyclea / Day
Time (Event)
(Relative to BMS-813160 Dosing)
Hour: Minb
PK Plasma
Samplec
Cycle 1
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
00:30
X
2:00
X
Cycle 1 
Day 8
0 h (pre-dose)
00:00d
X
Cycle 1
Day 15e
OR
Cycle 2
Day 1f
0 h (pre-dose)
00:00d
X
00:30
X
1:00
X
2:00
X
3:00
X
4:00
X
6:00
X
8:00
X
Cycle 1
Day 16e
OR
Cycle 2
Day 2f
0 h (pre-dose)
00:00d
X
Cycle 3
Day 1
0 h (pre-dose)
00:00d
X
00:30
X
2:00
X
Cycle 5
Day 1
0 h (pre-dose)
00:00d
X
a 1 cycle = 4 weeks.
b The following windows serve as a guideline for PK sample collections and will be considered within window:
   •  ± 2 minutes for samples within the first 4 hours after dose.
   •  ± 15 minutes for samples after the first 4 hours through 24 hours after dose.
   •  ± 1 h for the remaining time points following 24 hours after dose.
c For the measurement of BMS-813160 and the metabolite BMS-939429 (M1). Apply to both BID and QD regimens 
in all combination arms. BMS-813160 should be administered at (1 hour window) the start of chemotherapy.
d Sample collected 12 h (BID regimen) or 24 h (QD regimen) after the previous dose (trough sample) and prior to 
the dose on that day.
e For Gem/nab-paclitaxel combination therapy, BMS-813160 PK samples will be collected on Cycle 1 Day 15 and 
Cycle 1 Day 16.
f For FOLFIRI combination therapy, BMS-813160 PK samples will be collected on Cycle 2 Day 1 and Cycle 2 
Day 2.
Revised Protocol No.: 06
Date: 05-Dec-2019
120
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
9.5.3
Pharmacokinetic Assessment of BMS-813160, and Pharmacokinetic 
and Immunogenicity Assessment of Nivolumab in Part 1 (Arm C), and 
Part 2 (Arm C and Arm D)
Blood samples for BMS-813160 and metabolite BMS-939429 (M1) PK will be collected for all 
participants receiving BMS-813160 alone (Arm D [Part 2]), or in combination with nivolumab 
(Arm C [Part 1 and Part 2]).
Blood samples for nivolumab PK and immunogenicity assessments will be collected for all 
participants receiving nivolumab (Arm C [Part 1 and Part 2]).
Table 9.5.3-1 lists the blood sampling schedule to be followed for the assessment of PK of 
BMS-813160 and PK and immunogenicity of nivolumab. Further details of blood collection and 
processing will be provided to the site in the procedure manual.
Table 9.5.3-1:
Pharmacokinetic and Immunogenicity Sampling Schedule for 
BMS813160 and Nivolumab in Part 1 (Arm C), and Part 2 
(Arm C [Including Cross Over] and Arm D)
Sample Collection Time
Nivolumab
Immunogenicity
Serum Sampled
Study
Cyclea / Day
Time (Event)
Hour
Time
(Relative To Dosing)
Hour: Minb
BMS-813160
Plasma
Samplec
Nivolumab
PK Serum
Sampled
Cycle 1
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
X
X
EOI
00:30
X
X
2:00
X
Cycle 1
Day 15
0 h (pre-dose)
00:00
X
X
Cycle 2
Day 1
0 h (pre-dose)
00:00
X
X
2:00
X
X
Cycle 3
Day 1
0 h (pre-dose)
00:00
X
X
X
2:00
X
Cycle 5
Day 1
0 h (pre-dose)
00:00
X
X
X
Cycle 9
Day 1
0 h (pre-dose)
00:00
X
X
a 1 cycle = 4 weeks.
b The following windows serve as a guideline for PK sample collections and will be considered within window:
   •  ± 2 minutes for samples within the first 4 hours after dose.
   •  ± 15 minutes for samples after the first 4 hours through 24 hours after dose.
   •  ± 1 h for the remaining time points following 24 hours after dose.
c For the measurement of BMS-813160 and the metabolite BMS-939429 (M1). Apply to both BID and QD regimens 
in all combination arms. BMS-813160 should be administered at the start of nivolumab infusion to minimize blood 
draws.
d Nivolumab PK and immunogenicity samples should only be drawn from participants receiving nivolumab in Arm C 
(Part 1 and Part 2). Pre-dose samples should be taken just prior to the start of infusion (preferably within 
Revised Protocol No.: 06
Date: 05-Dec-2019
121
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
30 minutes). If the infusion is delayed and a pre-dose sample is already collected, there is no need to collect an 
additional pre-dose sample. End-of-infusion (EOI) samples should be taken as close to EOI as possible (preferably 
2 minutes prior to EOI) on the contralateral arm (ie, the arm not used for the infusion).
9.5.4
Pharmacokinetic Assessment of Irinotecan, Nab-Paclitaxel, and BMS-
813160, and Pharmacokinetic and Immunogenicity Assessment of 
Nivolumab in Part 2 (Arm A and Arm B)
The intensive PK sampling strategy in Table 9.5.4-1 will be followed in a subset of participants 
(approximately 12 per cohort) for Arm A (all cohorts) and Arm B (Cohorts 3a and 3c) in Part 2. 
Once the number of participants needed is reached, the Sponsor will notify the sites that sparse PK 
samples will be collected for the remaining participants in these cohorts as described in Table 
9.5.4-2. 
Plasma samples for irinotecan and its metabolite SN-38 will be collected for a subset of 
participants (approximately 12 per cohort) for Arm A in Part 2 who receive the FOLFIRI 
combination treatment as described in Table 9.5.4-1. Plasma samples for nab-paclitaxel will be 
collected for a subset of participants (approximately 12 per cohort) for Arm B (Cohorts 3a and 3c) 
in Part 2 who receive the Gem/nab-paclitaxel combination treatment as described in Table 9.5.4-
1. Blood samples for BMS-813160 and metabolite BMS-939429 (M1) PK, and blood samples for 
nivolumab PK and immunogenicity assessments will also be collected as described in Table 9.5.4-
1.
Individual PK parameters will be derived by non-compartmental methods by a validated PK 
analysis program.
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-24)
Area under the concentration-time curve from time 0 to 24 hours post 
dose
Ctrough
Trough observed plasma concentration
Sparse blood samples will be collected for BMS-813160 PK, nivolumab PK and immunogenicity 
assessments for the remaining participants in Arms A (all cohorts) and B (Cohorts 3a and 3c), and 
all participants in Cohort 3b of Arm B as described in Table 9.5.4-2.
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
Revised Protocol No.: 06
Date: 05-Dec-2019
122
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.5.4-1:
Intensive Pharmacokinetic Sampling Schedule for FOLFIRI 
(Irinotecan), Abraxane (Nab-Paclitaxel), and BMS813160 for Arms 
A (all Cohorts) and B (Cohorts 3a and 3c) in Part 2 - Approximately 
12 Participants in each Cohort
Sample Collection Timea
Study
Cycleb/Day
Time (Event)
Time
(Relative to 
Dosing)c,d
Hour: Min
Irinotecan
PK Plasma
Samplee
(Arm A)
Nab-Paclitaxel
PK Plasma
Sample
(Cohorts 3a & 3c
of Arm B)
BMS-813160 PK
Plasma Samplef
(Cohorts 1a & 1b
of Arm A; Cohort 3a 
of Arm B)
Cycle 1
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
X
X
2:00
X
X
X
Cycle 1
Day 15
0 h (pre-dose)
00:00 (pre-dose)
X
X
X
2:00
X
X
X
Cycle 2
Day 1
0 h (pre-dose)g
00:00
X
X
X
0.5 h (EOI)h
0:30
X
X
1 h 30 min (EOI)h
1:30
X
X
2:00
X
X
4:00
X
X
X
8:00
X
X
X
Cycle 2
Day 2
24 h
24:00
X
X
X
Cycle 3
Day 1
0 h (pre-dose)
00:00
X
2:00
X
Cycle 5
Day 1
0 h (pre-dose)
00:00
X
Cycle 9
Day 1
0 h (pre-dose)
00:00
a The intensive PK sampling strategy in Table 9.5.4-1 will be followed in a subset of participants (approximately 12 
per cohort) for Arm A (all cohorts) and Arm B (Cohorts 3a and 3c) in Part 2. Once the number of participants 
needed is reached, the Sponsor will notify the sites that sparse PK samples will be collected for the remaining 
participants in these cohorts as described in Table 9.5.4-2.
b 1 cycle = 4 weeks.
c Pre-dose samples should be taken just prior to the administration of the first drug (preferably within 30 minutes) 
during that day. If BMS-813160 dose or the infusion is delayed and a pre-dose sample is already collected, there is 
no need to collect an additional pre-dose sample. Sampling time other than pre-dose sample is relative to the dosing 
for the PK sample being collected (ie, sample for chemotherapy or BMS-813160). BMS-813160 should be 
administered at the start of irinotecan and nab-paclitaxel infusions to minimize blood draws.
d The following windows serve as a guideline for PK sample collections and will be considered within window:
   •  ± 2 minutes for samples within the first 4 hours after dose.
   •  ± 15 minutes for samples after the first 4 hours through 24 hours after dose.
   •  ± 1 h for the remaining time points following 24 hours after dose.
e For the measurement of irinotecan and its metabolite SN-38.
f For the measurement of BMS-813160 and the metabolite BMS-939429 (M1). Samples should only be drawn from 
participants receiving BMS-813160 in Cohorts 1a and 1b of Arm A, and Cohort 3a of Arm B.
Revised Protocol No.: 06
Date: 05-Dec-2019
123
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
g Participants are required to fast for at least 8 hours prior to the C2D1, 0 hour (pre-dose) PK sample collections.
h End of infusion (EOI) samples should be taken as close to end of the infusion of irinotecan or nab-paclitaxel as 
possible (preferably within 2 minutes before the end of the infusion) on the contralateral arm (ie, the arm not used 
for the infusion).
Revised Protocol No.: 06
Date: 05-Dec-2019
124
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.5.4-2:
Sparse Pharmacokinetic Sampling Schedule for BMS 813160 and 
Nivolumab for Arms A and B (Part 2) - Remaining Participants and 
All Participants in Cohort 3b (Arm B)
Sample Collection Time
BMS-813160 PK
Nivolumab
Study
Cyclea/Day
Time (Event)
Time
(Relative to Dosing)
Hour: Minb,c
Plasma Sampled
(Cohorts 1a & 1b of 
Arm A; Cohorts 3a 
& 3b of Arm B)
Nivolumab PK
Serum Samplee
(Cohort 3b of
Arm B only)
Immunogenicity
Serum Samplee
(Cohort 3b of
Arm B only)
Cycle 1
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
X
X
2:00
X
X
Cycle 1
Day 15
0 h (pre-dose)
00:00
X
X
Cycle 2
Day 1
0 h (pre-dose)
00:00 (pre-dose)
X
X
2:00
X
X
Cycle 3
Day 1
0 h (pre-dose)
00:00
X
X
X
2:00
X
Cycle 5
Day 1
0 h (pre-dose)
00:00
X
X
X
Cycle 9
Day 1
0 h (pre-dose)
00:00
X
X
a 1 cycle = 4 weeks.
b Pre-dose samples should be taken just prior to the administration of the first drug (preferably within 30 minutes) 
during that day. If BMS-813160 dose or the infusion is delayed and a pre-dose sample is already collected, there is 
no need to collect an additional pre-dose sample. Sampling time other than pre-dose sample is relative to the dosing 
for the PK sample being collected (ie, sample for BMS-813160 or nivolumab). BMS-813160 should be 
administered at the start of irinotecan, nab-paclitaxel, or nivolumab infusion.
c ± 2 days for sparse sampling or as noted in the protocol.
d For the measurement of BMS-813160 and the metabolite BMS-939429 (M1). BMS-813160 PK samples should 
only be drawn from participants receiving BMS-813160 in Cohorts 1a and 1b of Arm A, and in Cohorts 3a and 3b 
of Arm B.
e Nivolumab PK and immunogenicity samples should only be drawn from participants receiving nivolumab in 
Cohort 3b of Arm B.
9.5.5
Pharmacokinetic Sample Analyses
The plasma and urine samples will be analyzed for BMS-813160 and BMS-939429 by a validated 
LC-MS/MS assay and for NMN and creatinine (MATE-renal transporter biomarkers) with a 
qualified LC-MS/MS method. Serum samples will be analyzed for nivolumab by a validated assay. 
Plasma samples will be analyzed for irinotecan, SN-38, and nab-paclitaxel by a validated 
LC-MS/MS assay.
In addition, after the scheduled analyses are complete, plasma and urine samples will be archived 
for potential analysis of BMS-813160 metabolites, analysis of co-administered drugs and their 
metabolites, and/or biomarker analyses related to MATE function, if the need arises and to the 
extent possible.
Revised Protocol No.: 06
Date: 05-Dec-2019
125
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual.
9.6
Pharmacodynamics
The effect of dosing regimen on pharmacodynamics of BMS-813160 will be assessed via 
comparison of the modulation of CCR2 and CCR5 activity, including changes of intra-tumor 
markers (eg, Treg, TAM or MDSC), and/or changes of peripheral markers (eg, MCP-1, monocyte 
count, and CCR5 phosphorylation) in the different doses of BMS-813160 being investigated in 
this study. Data from this study may be pooled with that from other studies to perform 
PK/pharmacodynamic analyses. Results of PK/ pharmacodynamic analyses will be reported 
separately if performed.
Pharmacodynamic measures (in the form of biomarker assessments) may be assessed for 
associations with clinical outcomes. There will be various types of specimens obtained for 
biomarker testing: whole blood, plasma, serum, peripheral blood monocytes, tumor tissue, and 
stool sample. The sample subtypes and testing plans associated with each are described in Section 
9.8. Complete instructions on the collection, processing, handling, and shipment of all samples 
described herein will be provided in a separate Laboratory Procedures Manual.
9.7
Pharmacogenomics
The final disposition of samples will be conducted per local regulations.
9.7.1
Whole Blood DNA Sampling
A 6-mL whole blood sample will be drawn at screening (refer to Whole Blood DNA collection in 
Table 9.8-1 and Table 9.8-2) for potential analysis of DNA variants in ADME-related genes (see 
Appendix 12 which contains the lists of ADME-related genes from http://pharmaadme.org) and 
genes related to MATE1 and MATE2-K transporters (SLC47A1 and SLC47A2, respectively). 
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
9.8
Biomarkers
Tumor, blood, and stool samples will be drawn at the times indicated in Table 9.8-1 (Part 1) and 
Table 9.8-2 (Part 2) for biomarker analyses. Blood and urine samples will be drawn during the 
BMS-813160 monotherapy period in conjunction with the sampling for PK assessments (See 
Section 9.5.1, Table 9.5.1-1) for NMN and creatinine (MATE-renal transporter biomarkers). 
Further details of sample collection and processing for these biomarkers will be provided to the 
site in the procedure manual.
Revised Protocol No.: 06
Date: 05-Dec-2019
126
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.8-1:
Biomarker Sampling Schedule - Part 1
Sample Collection Timea
Tumor
Whole Blood Sample
Serum
Cytokine
Analysis
Stool
Study
Cycleb / Day
Time
(Event)
Hour
SNPc
Immuno-
Phenotyping
Phospho-
CCR5
Plasma
Sample 
for
ctDNA
Screening
Xd
X
X
X
Cycle 0
Day 1
0 h
(pre-dose)
X
X
X
X
2 h
X
X
X
4 h
X
X
X
8 h
X
X
X
Cycle 0
Day 2
0 h
X
X
X
Cycle 0
Day 7
0 h
(pre-dose)
X
X
X
Cycle 0
Day 14
0 h
(pre-dose)
Xe
(Arms A, B, and C)
X
X
X
2 h
X
X
4 h
X
X
8 h
X
X
X
Cycle 1
Day 1
0 h
(pre-dose)
X
X
X
Cycle 1
Day 15
0 h
(pre-dose)
X
(Arm C only)
X
X
X
Cycle 2
Day 1
0 h
(pre-dose)
X
X
X
Cycle 3
Day 1
0 h
(pre-dose)
X
X
X
Cycle 5
Day 1
0 h
(pre-dose)
X
X
X
Q8W 
following 
C5D1f
X
X
X
EOT/Disease
progressiong
Xg
X
X
X
Abbreviations: C5D1 = Cycle 5, Day 1; CCR5 = cysteine-cysteine chemokine receptor 5; ctDNA = circulating tumor 
deoxyribonucleic acid; EOT = end of treatment; MDSC = myeloid-derived suppressor cells; Q8W = every 8 weeks; 
SNP = single nucleotide polymorphism; Treg = regulatory T cells 
a All biomarker samples should be obtained at treatment visits corresponding to the indicated time points.
b 1 cycle = 4 weeks, except for Cycle 0 (2 weeks).
c Whole Blood DNA collection. Genotyping sample will be collected.
d Pre-treatment biopsy can be collected during screening or in the preceding 90 days (refer to Section 6.1 for inclusion 
criteria).
e Tumor biopsy (fresh) is mandatory (−3 day window).
f This would align with the response assessment Q8W beginning on C5D1.
g Biopsies upon disease progression are optional but encouraged.
Revised Protocol No.: 06
Date: 05-Dec-2019
127
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 9.8-2:
Biomarker Sampling Schedule - Part 2 (Including Cross Over)
Sample Collection Timea
Tumor
IHC
WES/GEP
Whole Blood Sample
Serum
Cytokine
Analysis
Plasma
Sample
for
ctDNA
Stool
Study
Cycleb / Day
Time
(Event)
Hour
SNPc
Immuno-
Phenotyping
GEP,
TCR
Screening
Xd
X
X
X
Cross-over
Baseline
Xe
X
X
Cycle 1
Day 1
0 h
(pre-dose)
X
X
X
X
4 h
X
X
6 h
X
X
Cycle 1
Day 15
0 h
(pre-dose)
X
X
Cycle 1
Day 28f
0 h
(pre-dose)
Xg
X
X
X
X
4-6 h
X
X
Cycle 3
Day 1
0 h
(pre-dose)
X
X
X
X
Cycle 5
Day 1
0 h
(pre-dose)
X
X
X
X
Q8W
following
C5D1h
0 h
(pre-dose)
X
X
X
X
Pre-Cross Over/
EOT/Disease
progressioni
X
X
X
X
EOT/Disease
progressionj
Xk
X
X
X
X
Abbreviations: C5D1 = Cycle 5, Day 1; CCR5 = cysteine-cysteine chemokine receptor 5; ctDNA = circulating tumor 
deoxyribonucleic acid; EOT = end of treatment; GEP = gene expression profile; IHC = immunohistochemistry; 
Q8W = every 8 weeks; SNP = single nucleotide polymorphism; TCR = T-cell repertoire (T-cell receptor clonality); 
WES = whole-exome sequencing
a All biomarker samples should be obtained at treatment visits corresponding to the indicated time points.
b 1 cycle = 4 weeks
c Whole Blood DNA collection. Genotyping sample will be collected.
d Pre-treatment biopsy can be collected during screening or in the preceding 90 days (refer to Section 6.1 for inclusion 
criteria).
e Participants in cross-over cohort will be required to undergo a pre-treatment biopsy.
f Whole blood, serum, and plasma samples can be collected on C2D1 instead of C1D28. Pre-dose and 4-6 hour post 
dose samples will be collected with respect to irinotecan in Cohort 1c and nab-paclitaxel in Cohort 3c. In all other 
cohorts, samples are collected prior to and 4-6 hour post BMS-813160 administration.
g Tumor biopsy is mandatory (−3 day window). 
h This will align with the response assessment Q8W beginning on C5D1.
i
Cohort 1c cross-over participants only.
j
All participants including cross-over participants at the time of subsequent progression. 
Revised Protocol No.: 06
Date: 05-Dec-2019
128
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
k Biopsies upon disease progression are optional, but encouraged for all combination therapy arms.
For PD-L1 and biomarker research testing, tumor tissue (FFPE archival or recent acquisition) must 
be obtained during the screening period. If PD-L1 results are available, assay conditions and results 
will be collected. (Note: Fine needle aspiration and bone metastases samples are not acceptable 
for submission.) 
Detailed immune and tumor phenotyping will be pursued to build clinical data to support the 
clinical findings. The biomarker analyses will include but are not limited to the following: 
1) Systemic immune monitoring on circulating immune cells (eg, MDSC) and secreted cytokines 
(in particular, CCL2 and CCL5), chemokines, and other related soluble factors.
2) Examination of tumor-associated immune cells and microenvironment, through proteomics, 
histopathology (eg, CCR2, CCR5, MDSC, TAM, Treg, and CTL), next generation sequencing 
(NGS) and expression (mRNA) profiling.
3) Genomic analyses (DNA and/or RNA) on tumor, whole blood/PBMC, and cell-free DNA, for 
assessing tumor mutation burden, T-cell repertoire (TCR), dominant tumor clone(s), and 
gene-expression analyses.
4) Stool samples for microbiota analysis.
5) Plasma circulating tumor DNA (ctDNA) analysis.
Next generation DNA sequencing (testing may include but is not limited to whole exome and/or 
whole genome) may be performed on DNA isolated from peripheral genomic analysis of tumor 
samples at the time of enrollment and during the study, and association with ctDNA tested via 
established methods in plasma samples collected during treatment, may be tested for identification 
of tumor mutations. Blood samples will be drawn at the time points indicated in Table 9.8-1 and 
Table 9.8-2. RNA sequencing or other methods for gene expression profiling will also be utilized 
in blood and tumor samples.
The presence of cell-free DNA in circulating blood is a well-documented phenomenon.38
Fragments of DNA are shed into the blood stream from dividing cells during cell proliferation or 
cell death. In subjects with cancer, a fraction of this circulating DNA is derived from tumor and is 
termed ctDNA.39 Albeit small, fragments of DNA averaging between 800 to 200 base pairs and 
covering specific genomic regions can be amplified with PCR. Moreover, several studies have 
detected mutations in ctDNA that exactly correspond to mutations from the parent tumor.40,41
9.8.1
Additional Research Collection
This protocol will include residual sample storage for additional research (AR).
For All US sites:
Additional research is required for all study participants, except where prohibited by IRB/ethics 
committees, or academic/institutional requirements. Where 1 or more of these exceptions occurs, 
Revised Protocol No.: 06
Date: 05-Dec-2019
129
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
participation in the additional research should be encouraged but will not be a condition of overall 
study participation.
•
If the IRB/ethics committees and site agree to the mandatory additional research retention and 
/or collection, then the study participant must agree to the mandatory additional research as a 
requirement for inclusion in the study.
•
If optional participation is permitted and approved, then the study participants may opt out of 
the additional research retention and /or collection.
For non-US Sites
Additional research is optional for all study participants, except where retention and/or collection 
is prohibited by local laws or regulations, ethics committees, or institutional requirements. 
This collection for additional research is intended to expand the translational research and 
development (R&D) capability at BMS, and will support as yet undefined research aims that will 
advance our understanding of disease and options for treatment. It may also be used to support 
health authority requests for analysis, and advancement of pharmacodiagnostic development to 
better target drugs to the right patients. This may also include genetic/genomic exploration aimed 
at exploring disease pathways, progression, and response to treatment etc. 
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or Designee) to 
ensure the research supports appropriate and well-defined scientific research activities.
Residual tumor tissue and blood samples from biomarker collection and PK collections (see 
Table 9.8.1-1) will also be retained for additional research purposes.
Table 9.8.1-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time Point
Tumor biopsy and blood collection
Screening, on-treatment, and at disease progression
(if available)
Residual serum and plasma 
All biomarker collections and all PK collection
Note: If a biopsy has been performed and tissue is available, participants are requested to submit fresh tumor tissue at 
disease progression for biomarker research. Tissue submission is optional and biopsy is not required by protocol.
Samples kept for future research will be stored at the BMS Biorepository in 
 USA or 
an independent, BMS approved storage vendor.
•
The manager of these samples will ensure they are properly used throughout their usable life 
and will destroy the samples at the end of the scheduled storage period, no longer than fifteen 
(15) years after the end of the study or the maximum allowed by applicable law.
Revised Protocol No.: 06
Date: 05-Dec-2019
130
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
•
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Additional research samples will be retained for 15 years or the maximum allowed by applicable 
law. No additional sampling is required for residual collections. 
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
9.8.2
Immunogenicity Assessments
Blood samples for nivolumab immunogenicity analysis will be collected from Arm B (Cohort 3b, 
Part 2) and Arm C (Part 1 and Part 2) participants at time points specified in Table 9.5.3-1, Table 
9.5.4-1, and Table 9.5.4-2. Serum will be analyzed by validated immunogenicity assays. All on-
treatment immunogenicity sampling time points are intended to align with days on which study 
treatment is administered, if dosing occurs on a different day, the sampling should be adjusted 
accordingly. Selected serum samples may be analyzed by an exploratory method that measures 
anti-drug antibodies for technology exploration purposes; exploratory results will not be reported. 
In addition, serum samples designated for PK or biomarker assessments may also be used for 
immunogenicity analysis if required (eg, insufficient volume for complete immunogenicity 
assessment or to follow up on suspected immunogenicity-related AEs).
9.9
Health Economics OR Medical Resource Utilization and Health 
Economics
Not applicable.
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination 
This study will start with three treatment arms: BMS-813160 in combination with either FOLFIRI 
(Arm A), Gem + nab-paclitaxel (Arm B), or nivolumab (Arm C) in participants with advanced 
CRC or pancreatic cancer. Each arm consists of a Phase 1b treatment (Part 1) and a Phase 2 
efficacy expansion for combination treatments (Part 2). 
In Part 1 of treatment Arms A, B and C, approximately 6-9 evaluable participants per dose level 
per arm will be treated. This sample size provides each dose arm with about 80% probability to 
detect any AE with event rate of 24%. Approximately 6 additional participants may be added to 
each dose in each treatment arm or lower doses of BMS-813160 (150 mg QD and 300 mg QD).
In Part 2, the efficacy expansion phase of Arm A includes three cohorts (Cohorts 1a, 1b, and 1c) 
consisting of 2L CRC, the expansion phase of Arm B continues to focus on 1L pancreatic cancer 
(Cohorts 3a, 3b, and 3c), and the expansion of Arm C includes 2 cohorts (Cohorts 4 [closed per 
Revised Protocol 06] and 5): 2L pancreatic cancer and 2/3L CRC (MSS), respectively. 
Revised Protocol No.: 06
Date: 05-Dec-2019
131
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Approximately 35 evaluable participants per cohort will be treated in Arms A and B, and 
approximately 31 evaluable participants per cohort will be treated in Arm C. Arm D (BMS-813160 
monotherapy, opens only if an ORR of approximately 15% or durable responses are observed in 
Arm C) will include approximately 18 evaluable 2L pancreatic (Cohort 7) or 2/3L CRC MSS
(Cohort 8) participants. Each disease cohort expansion will be handled independently and there 
will be no multiplicity adjustment. The number of participants will be continuously monitored 
such that the number of evaluable participants in Part 2 will not exceed 40 evaluable participants 
in any cohort. With regard to sample size, participants who are reassigned to a different study 
treatment following treatment in another cohort will be counted once for each assignment.
Design operating characteristics for each of the Cohorts 4 (closed per Revised Protocol 06), 5, 7, 
and 8 are given in Table 10.1-1, which includes the sample size, the assumptions of historic ORR 
and true (target) ORR, the associated Type I error, power, and other applicable operating 
characteristics, although this is not used for statistical hypothesis testing. 
With a one-sided exact test at significance level 0.1, data from approximately 18 participants for 
Cohort 7 and Cohort 8 will provide 72% power to detect a target ORR of 20% against a reference 
ORR of 5% for Cohort 5 of Arm D. In addition, if 3 responses are observed in either cohort, (eg, 
17% observed response rate), the lower limit of the 90% one-sided CI using Clopper-Pearson 
method for the ORR is 6% (higher than historical ORR of 5%) and the distance to the point 
estimate is approximately 11%. If the assumed true response rate is 20%, there is a 73% probability 
of observing at least 3 responses; and the probability is only 6% if the true response rate is only 
5% rather than 20%.
The Fleming 2-stage design framework will be used as a guide for Cohorts 4 (closed per Revised 
Protocol 06) and 5 of Arm C.42,43 The assumed historic and target response rates may change over 
time and may need to be adjusted by the time of response data from this study are available. Using 
a 2-stage design provides an option for futility as well as preliminary antitumor activity for 
strong-go early on. Enrollment may continue into stage 2 while the planned number of participants 
for Stage 1 are reached for efficacy evaluable tumor assessments. There will be no stopping of a 
disease cohort for efficacy, although early plan for the next stage of clinical development may be 
initiated. 
As an example, guided by Table 10.1-1, approximately 18 3L CRC participants in Cohort 5, for 
example, will be treated in Arm C (BMS-813160 + nivolumab) in Stage 1. Assuming the true 
response rate is 20% in this population when treated with BMS-813160 + nivolumab if there are 
3 or more responses in 18 participants, it may trigger to plan early further clinical development 
after careful evaluation of all available data including duration of response and safety profile. The 
probability to observe such favorable response is approximately 73% if in fact the treatment is 
efficacious. If there are no responses in 18 treated participants, the cohort may be stopped for 
futility. The probability of early stopping for futility is approximately 40% if in fact the treatment 
is inefficacious, eg, 5%. If the number of responses are at least 1, an additional 13 participants may 
be treated to collect more data. At the end of Stage 2, if there are 3 or fewer responses, it may not 
warrant further clinical development. If there are 4 or more responses it may show evidence of 
treatment efficacy.
Revised Protocol No.: 06
Date: 05-Dec-2019
132
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Sample sizes for cohorts in Arms A and B are determined based on 1:1:1 randomization. Historical 
rates for the 2L colorectal and 1L pancreatic cohorts are approximately 15% and 25%, 
respectively.11,44,45,46,47,48 To facilitate clinical evaluation of data, point estimate and 80% 1-sided 
CI (or 60% 2-sided) for the difference between treatments will be assessed, and totality of the data 
will be used for decision-making. With 35 participants randomized to each of the treatments, the 
expected half-width of an 80% confidence interval for the difference in response rates between 
experimental and control is expected to be approximately 10% (eg, if the observed difference in 
rates [experimental - control] is 10%, then a difference less than 0% could be ruled out with 80% 
confidence). No adjustment has been made to reflect multiple comparisons. If results are 
sufficiently promising, then the protocol may be amended to expand the cohort to allow 
comparison between treatments with higher confidence.
Revised Protocol No.: 06
Date: 05-Dec-2019
133
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 10.1-1:
Example of Design Characteristics
Treatment Cohort (Indication)
Historic/
Target Rate
(%)
Stage
Cumulative
Sample
Size
Conclude
Inefficacy
if Ra
Conclude
Efficacy
if Ra
PETb for
Futility
(%)
PEEc for
Efficacy
(%)
Type I
Error
Power
One-Sample Fixed Design
Arm D: Cohort 7 (2L pancreatic)
Arm D: Cohort 8 (2/3L CRC [MSS])
5/20
18
 
 
0.1
0.72
Fleming’s Two-Stage Design
Arm C: Cohort 4 (2L pancreatic)
(Closed per Revised Protocol 06)
5/20
1
18
≤0
≥3
40
73
0.09
0.9
2
31
≤3 
≥4 
Arm C: Cohort 5 (2/3L CRC [MSS])
5/20
1
18
≤0 
≥3 
40
73
0.09
0.9
2
31
≤3 
≥4 
a R is the cumulative number of responses at the end of stage
b Probability of early termination (PET) if the historic rate is true
c Probability of early efficacy (PEE) signal if the target rate is true
Revised Protocol No.: 06
Date: 05-Dec-2019
134
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
10.2
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign informed consent and were registered into the IRT
Treated 
All participants who take at least 1 dose of study treatment
Response-evaluable
All treated participants with measurable disease at baseline and one of the following:
1) at least one post-baseline tumor assessment, 2) clinical progression, or 3) death
Pharmacokinetic
All treated participants who have evaluable concentration-time data
Immunogenicity
All nivolumab treated participants who have baseline and at least one post baseline 
immunogenicity assessment
Biomarker
All treated participants with available biomarker data
10.3
Statistical Analyses
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the selection of participants to be included in the analyses, and procedures for accounting 
for missing, unused, and spurious data. Below is a summary of planned statistical analyses of the 
primary and secondary endpoints.
A description of the participant population will be included in the statistical output reported, 
including subgroup of age, gender, and race.
10.3.1
Efficacy Analyses
The primary efficacy analyses will be performed on treated population for the final analysis. 
Efficacy analyses based on the response-evaluable population may be performed for interim 
analyses when the minimum follow-up period is less than sufficient to warrant adequate 
interpretation of the result. Details on censoring scheme on time-to-event endpoints such as 
duration of response (DOR) and PFS will be described in the SAP. Participants reassigned into 
Arm C cohorts following treatment in another cohort, will be combined with participants originally 
assigned in these cohorts for efficacy analysis. A sensitivity analysis excluding these participants 
may be performed, and details will be included in statistical analysis plan if applicable.
Revised Protocol No.: 06
Date: 05-Dec-2019
135
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Endpoint
Statistical Analysis Methods
ORR is defined as the proportion of all treated participants whose 
best overall response (BOR) is either CR or PR.
BOR for a participant will be assessed per RECIST v1.1 by 
investigator.
Estimate of ORR and corresponding two-sided 
exact 95% CI using the Clopper-Pearson 
method (stratified by tumor sidedness in Arm 
A and by prior neoadjuvant or adjuvant therapy 
in Arm B in Part 2; stratification was removed 
per Revised Protocol 06) by treatment for each 
tumor type
Estimate of difference in ORR between each 
treatment cohort and the control cohort of 
Arm A and Arm B and corresponding 
two-sided exact 95% CI (stratified by tumor 
sidedness in Arm A and by prior neoadjuvant 
or adjuvant therapy in Arm B in Part 2; 
stratification was removed per Revised 
Protocol 06) by treatment for each tumor type
Median DOR
DOR for a participant with a BOR of CR or PR, is defined as the 
time between the date of first response and the date of the first 
objectively documented tumor progression per RECIST v1.1 or 
death, whichever occurs first.
Median duration of response using the Kaplan-
Meier method and corresponding two-sided 
95% CI using Brookmeyer and Crowley 
methodology (using log-log transformation) 
[stratified by tumor sidedness in Arm A and by 
prior neoadjuvant or adjuvant therapy in Arm 
B in Part 2; stratification was removed per 
Revised Protocol 06] by treatment for each 
tumor type
PFSR at 24 weeks
PFS for a participant is defined as the time from the first dosing 
date to the date of first objectively documented disease 
progression or death due to any cause, whichever occurs first.
Estimate by the Kaplan-Meier method and 
corresponding 95% CI will be derived based on 
Greenwood formula (stratified by tumor 
sidedness in Arm A and by prior neoadjuvant 
or adjuvant therapy in Arm B in Part 2; 
stratification was removed per Revised 
Protocol 06) by treatment for each tumor type.
10.3.2
Safety Analyses
All safety analyses will be performed on the treated population.
Endpoint
Statistical Analysis Methods
Incidence of DLTs (Part 1 and Cohort 3b of Part 2 only), AEs, 
SAEs, AEs leading to discontinuation, deaths
AEs will be graded according to CTCAE v4.03.
DLT rate by dose level/arm (Part 1 and 
Cohort 3b in Part 2). Frequency distribution of 
treated participants with AE using the worst 
CTC grade. Participants will only be counted 
(1) once at the preferred term (PT) level, (2) 
once at the system organ class (SOC) level, and 
(3) once in the ‘Total subject’ row at their worst 
CTC grade, regardless of SOC or PT.
Summary measures of vital signs and lab clinical test results
Lab abnormalities
Laboratory values will be graded according to CTCAE v4.03.
Vital signs and clinical laboratory test results 
will be listed and summarized
Lab shift table using the worst CTC grade on 
treatment per participant
Revised Protocol No.: 06
Date: 05-Dec-2019
136
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
10.3.3
Pharmacokinetic Analyses
Endpoint
Statistical Analysis Methods
Cmax, Tmax, AUC(0-8), AUC(0-24), C24, CLT/F, AI_AUC, 
AI_Cmax, MR_Cmax, MR_AUC(0-24), %UR, CLR
Summary statistics: geometric means and 
coefficients of variation
Tmax
Summary statistics: medians and ranges
Ctrough
Summary statistics to assess attainment of 
steady state: geometric means and coefficients 
of variation; plots vs time by dose
Pharmacokinetic time-concentration data may be pooled with data from other studies for 
population PK analysis, which will be presented in a separate report.
10.3.3.1
BMS-813160 in Monotherapy Phase
Summary statistics will be tabulated for the PK parameters by dose and study day, for each analyte. 
Geometric means and coefficients of variation will be presented for Cmax, AUC(0-8), AUC(0-24), 
C24, CLT/F, CLR, and AI for BMS-813160. In addition, geometric means and coefficients of 
variation of MR_Cmax and MR_AUC(0-24) will be presented for metabolite, if data permit. 
Geometric means and coefficients of variation of %UR and CLR will be presented for 
BMS-813160. Medians and ranges will be presented for Tmax. Means and standard deviations 
will be presented for other PK parameters. 
Summary statistics will also be tabulated for trough plasma concentrations by study day, for each 
analyte. Geometric mean trough plasma concentrations will be plotted by study day for each 
analyte.
10.3.3.2
BMS-813160 in Combination Phase
To assess the effect of Gem/nab-paclitaxel or FOLFIRI on the PK of BMS-813160, point estimates 
and 90% confidence intervals will be calculated for the geometric mean ratios of Cmax, and 
AUC(0-24)/AUC(0-8) with chemotherapy treatment (combination phase) and
without 
chemotherapy (monotherapy phase) in each arm. These estimates will be based on the results of a 
linear mixed model analysis for each arm on log(Cmax), and log(AUC(0-24))/ log(AUC(0-8)) 
with treatment (with/without chemotherapy) as a fixed effect and subject as repeated measurement.
Plasma concentration data will be tabulated using summary statistics. These data, together with 
data from the monotherapy, may also be pooled with other datasets for PPK analysis, which will 
be presented in a separate report.
10.3.3.3
Nivolumab in Combination Phase
End-of-infusion and trough (Ctrough) concentrations for nivolumab will be tabulated using 
summary statistics. These data may also be pooled with other datasets from nivolumab studies for 
PPK analysis, which will be presented in a separate report.
Revised Protocol No.: 06
Date: 05-Dec-2019
137
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
10.3.4
Irinotecan and Nab-Paclitaxel in Combination Phase (Part 2)
Summary statistics will be provided for the PK parameters of nab-paclitaxel, irinotecan and SN-
38, by chemotherapy treatment group. Geometric means and coefficients of variation will be 
presented for Cmax, AUC(0-24), and Ctrough for nab-paclitaxel, irinotecan, and SN-38. Medians 
and ranges will be presented for Tmax. These PK parameters will be compared with the historical 
data to assess if BMS-813160 has any effect on the PK of nab-paclitaxel and irinotecan.
10.3.5
Immunogenicity Analyses
Endpoint
Statistical Analysis Methods
Incidence of ADA to nivolumab
Baseline ADA-positive participant is defined as a participant who 
has an ADA detected sample at baseline.a ADA-positive 
participant is a participant with at least 1 ADA-positive sample 
relative to baseline after initiation of the treatment
Frequency 
distribution 
of 
baseline 
ADA-positive participants and ADA-positive 
participants after initiation of the treatment
a Baseline sample is the last sample before initiation of the treatment
A listing of all available immunogenicity data will be provided by dose, and immunogenicity 
status. The frequency of participants with a baseline and/or at least 1 positive ADA assessment of 
nivolumab will be summarized.
10.3.6
Biomarker Analyses
Endpoint
Statistical Analysis Methods
Summary measures of change (or % change) from baseline in 
various biomarkers in the tumor (such as Treg & TAM) and 
peripheral blood
Summary statistics by planned study day and 
dose in each arm; Plots of the time course of 
biomarkers
Summary measures of RO level
Summary statistics/plots by planned study day 
and dose in each arm
10.3.7
ECG Analyses
All ECG data analyses including summaries of each ECG parameter, frequency distribution of 
participants’ maximum values/changes, and scatter plots will be performed following the current 
practice of ECG data analysis. Concentration-response analysis may be performed using a mixed 
effect model, if appropriate and applicable. The details of ECG data analysis will be provided in 
the SAP.
10.3.8
Other Analyses
The exploratory objective related to OS will be assessed by OS rate at certain time points (eg, 1 
year and 2 years) by the Kaplan-Meier method and corresponding 95% CI will be derived based 
on Greenwood formula by study treatment for each tumor type. OS rate is defined as the proportion 
of participants who are alive at the time point. OS for a participant is defined as the time from the 
first dosing date to the date of death due to any cause. 
Revised Protocol No.: 06
Date: 05-Dec-2019
138
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
PD biomarker exploratory analyses will be described in detail in the SAP finalized before database 
lock. The PPK analysis and PD analysis may be presented separately from the main clinical study 
report.
DNA variants in ADME-related genes from the Core and Extended ADME gene lists (see 
Appendix 12 which contains ADME gene lists from http://pharmaadme.org) as well as genes 
related to MATE1 and MATE2-K transporters (SLC47A1 and SLC47A2, respectively), will be 
determined, if deemed necessary.
10.3.9
Interim Analyses
Expansion phase of Arm C employs a 2-stage design framework and, therefore, there will be 
interim analysis as planned when adequate number of participants have response-evaluable data. 
Additional interim analyses may also be performed for administrative purposes or publications. 
No formal inferences requiring any adjustment to statistical significance level will be performed.
Revised Protocol No.: 06
Date: 05-Dec-2019
139
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
11
REFERENCES
1
Sanford DE, Belt BA, Panni RZ, et al. Inflammatory monocyte mobilization decreases patient 
survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res 
2013;19:3404-15.
2
Mitchem JB, Brennan DJ, Knolhoff BL, et al. Targeting tumor-infiltrating macrophages 
decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic 
responses. Cancer Res 2013;73:1128-41.
3
Halama N, Michel S, Kloor M, et al. Localization and density of immune cells in the invasive 
margin of human colorectal cancer liver metastases are prognostic for response to 
chemotherapy. Cancer Res 2011;71:5670-7.
4
Halama N, Zoernig I, Berthel A, et al. Tumoral Immune Cell Exploitation in Colorectal Cancer 
Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients. Cancer 
Cell 2016;29:587-601.
5
Afik R, Zigmond E, Vugman M, et al. Tumor macrophages are pivotal constructors of tumor 
collagenous matrix. J Exp Med. 2016;213:2315-31.
6
Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages 
with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline 
resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, 
non-randomised, phase 1b trial. Lancet Oncol 2016;17:651-62.
7
Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse 
sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 
2004;22:229-37.
8
Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of First-Line Chemotherapy Combined 
With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type
Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA 
2017;317:2392-2401.
9
Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in 
metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013 
Jan;14:29-37.
10 Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, 
fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: 
results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 
2007;25:1539-44.
11 Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with 
nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703.
12 Mahipal A, Grothey A. Role of Biologics in First-Line Treatment of Colorectal Cancer. J 
Oncol Pract. 2016;12:1219-1228.
Revised Protocol No.: 06
Date: 05-Dec-2019
140
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
13 Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and 
folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy
(NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 2016;387:545-57.
14 Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory 
metastatic colorectal cancer. N Engl J Med 2015;372:1909-19.
15 Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated 
metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-
controlled, phase 3 trial. Lancet 2013;381:303-12.
16 Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. 
N Engl J Med 2015;372:2509-20.
17 Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients 
with advanced cancer. N Engl J Med 2012;366:2455-65.
18 Bimbaum DJ, Finetti P, Lopresti A, et al. Prognostic value of PDL1 expression in pancreatic 
cancer. Oncotarget 2016;7:71198-71210.
19 Zhu Y, Knolhoff BL, Meyer MA, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating 
macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer 
models. Cancer Res 2014;74:5057-69.
20 Bendell JC, Kim TW, Goh BC, et al. Clinical activity and safety of cobimetinib (cobi) and 
atezolizumab in colorectal cancer (CRC). J Clin Oncol 2016;34(Suppl):Abstract 3502.
21 Nowak AK, Robinson BW, Lake RA. Synergy between chemotherapy and immunotherapy in 
the treatment of established murine solid tumors. Cancer Res 2003;63:4490-6.
22 Zheng H, Zeltsman M, Zauderer MG, et al. Chemotherapy-induced immunomodulation in non-
small-cell lung cancer: a rationale for combination chemoimmunotherapy. Immunotherapy 
2017;9:913-927.
23 Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in 
Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2018. doi:10.1056/NEJMoa1801005. 
[Epub ahead of print]
24 Reck M, Socinski MA, Cappuzzo F, et al. Primary PFS and safety analyses of a randomized 
phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 
1L non-squamous metastatic nsclc (IMPOWER150). Annals of Oncology 2017;28(Suppl 
11):mdx760.002 (https://doi.org/10.1093/annonc/mdx760.002).
25 Wainberg ZA, Hochster HS, Kim EJ, et al. Phase I study of nivolumab (Nivo) + nab-paclitaxel 
(nab-P) + gemcitabine (Gem) in advanced pancreatic cancer (APC). J Clin Oncol 2019 
37(Suppl):Abstract 298.
26 Wainberg ZA, Hochster HS, George B, et al. Phase I study of nivolumab (nivo) + nab-
paclitaxel (nab-P) ± gemcitabine (Gem) in solid tumors: Interim results from the pancreatic 
cancer (PC) cohorts. J Clin Oncol 2017;35(Suppl):Abstract 412.
Revised Protocol No.: 06
Date: 05-Dec-2019
141
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
27 CCR2/5 Dual Antagonist (BMS-813160) Investigator Brochure. Bristol-Myers Squibb 
Research and Development. Document Control No. 930039621.
28 Tanabe Y, Sasaki S, Mukaida N, et al. Blockade of the chemokine receptor, CCR5, reduces 
the growth of orthotopically injected colon cancer cells via limiting cancer-associated 
fibroblast accumulation. Oncotarget 2016;7:48335-48345.
29 BMS-813160: Placebo-controlled ascending single-dose study to evaluate the safety, 
pharmacokinetics and pharmacodynamics of BMS-813160 in healthy subjects (Study 
CV202001). Bristol Myers-Squibb Company; 2011. Document Control No. 930054784.
30 BMS-813160: Placebo-controlled, ascending multiple-dose study to evaluate the safety, 
pharmacokinetics and pharmacodynamics of BMS-813160 in healthy subjects (Study 
CV202002). Bristol Myers-Squibb Company; 2012. Document Control No. 930059372.
31 BMS-813160: A study to assess the bioavailability of BMS-813160 in a capsule formulation 
relative to BMS-813160 in solution and the effect of a high fat meal on the bioavailability of 
BMS-813160 in the capsule formulation in healthy subjects (Study CV202005). Bristol-Myers 
Squibb Company; 2012. Document Control No. 930058601.
32 Nivolumab (Opdivo) US Prescribing Information. Bristol-Myers Squibb Company; Revised 
May 2016.
33 Nivolumab (BMS-936558, MDX1106, ONO-4538) Investigator Brochure. Bristol-Myers 
Squibb Research and Development; 2018. Document Control No. 930038243.
34 BMS-813160: A double-blind, placebo-controlled, randomized, two-stage, parallel-group 
adaptive design Phase 2a study to evaluate the effects of BMS-813160 in subjects with type 2 
diabetes mellitus and diabetic kidney disease (DKD) who have residual macroalbuminuria 
despite treatment with an inhibitor of the renin-angiotensin system (Study CV202010). Bristol-
Myers Squibb Company; 2015. Document Control No. 930095738.
35 CAMPTOSAR® US Package Insert. Pfizer Inc; 2014.
36 ABRAXANE® US Package Insert. Celgene Corporation; 2015.
37 Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity 
in solid tumors: immune related response criteria. Clin Cancer Res. 2009;15:7412-20.
38 Thierry AR, El Messaoudi S, Gahan PB, et al. Origins, structures, and functions of circulating 
DNA in oncology. Cancer Metastasis Rev 2016;35:347-76.
39 Stroun M, Anker P, Maurice P, et al. Neoplastic characteristics of the DNA found in the plasma 
of cancer patients. Oncology 1989;46:318-22.
40 Kidess D, Heirich K, Wiggin M, et al. Mutation profiling of tumor DNA from plasma and 
tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation 
detection platform.Oncotarget 2015;6:2549–2561.
41 Ma M, Zhu H, Zhang C, et al. "Liquid biopsy" ctDNA detection with great potential and 
challenges. Ann Transl Med 2015;3:235.
Revised Protocol No.: 06
Date: 05-Dec-2019
142
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
42 Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 
1982;38:143-51.
43 Kramar A, Potvin D, Hill C. Multistage designs for phase II clinical trials: statistical issues in 
cancer research. Br J Cancer 1996;74:1317-20.
44 Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine Plus nab-Paclitaxel Is an Active 
Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. J Clin Oncol 
2011;29:4548-4554.
45 Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with 
secondline FOLFIRI in patients with metastatic colorectal carcinoma that progressed during 
or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a 
randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 2015;16:499–508.
46 Beretta GD, Fausto Petrelli F, Stinco S, et al. FOLFIRI + bevacizumab as second-line therapy 
for metastatic colorectal cancer pretreated with oxaliplatin: a pooled analysis of published 
trials. Med Oncol 2013;30:486-493.
47 Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: Randomized Phase II Study of 
PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients 
With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. J Clin Oncol 2017;36:359-
366.
48 Iwamoto S, Takahashi T, Tamagawa H, et al. FOLFIRI plus bevacizumab as second-line 
therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus 
oxaliplatin-based therapy: the randomized phase III EAGLE study. Annals of Oncology 
2015;26:1427–1433.
Revised Protocol No.: 06
Date: 05-Dec-2019
143
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
12
APPENDICES
Revised Protocol No.: 06
Date: 05-Dec-2019
144
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
%UR
percent urinary recovery over dosing interval; percent urinary recovery 
over 24 hours corrected for molecular weight
1L
first line
2L
second line
3L
third line
5-FU
5-fluorouracil 
ADA
anti-drug antibody
AE
adverse event
AI
accumulation index, calculated based on ratio of AUC(TAU) and Cmax 
at steady state to after the first dose
ALT
alanine aminotransferase 
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the curve
AUC(0-8)
area under the concentration-time curve from time 0 to 8 hours post dose
AUC(0-24)
area under the plasma concentration-time curve from time zero to 
24 hours post dose
AUC(0-T) 
area under the plasma concentration-time curve from time zero to the 
time of last quantifiable plasma concentration
AUC(INF)
area under the plasma concentration-time curve from time zero 
extrapolated to infinite time
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
BICR
blinded independent central review
BID
twice per day
BMI
body mass index
BMS
Bristol-Myers Squibb Company
BP
blood pressure
BOR
best overall response
BUN
blood urea nitrogen 
C24
observed plasma concentration at 24 hours post dose
Cavgss
average steady-state concentrations
Revised Protocol No.: 06
Date: 05-Dec-2019
145
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
C-C
cysteine-cysteine
CCL2
chemokine (C-C motif) ligand 2
CCL5
chemokine (C-C motif) ligand 5
CCR1
cysteine-cysteine (C-C) chemokine receptor 1
CCR2
cysteine-cysteine (C-C) chemokine receptor 2 
CCR4
cysteine-cysteine (C-C) chemokine receptor 4
CCR5
cysteine-cysteine (C-C) chemokine receptor 5 
cHL
classical Hodgkin lymphoma
CI
confidence interval
CL
clearance
CLR
renal clearance 
CLT/F
apparent total body clearance
Cmax
maximum observed plasma concentration
Cmaxss
maximum observed plasma concentration at steady state
Cminss
trough concentration at steady state
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
CR
complete response 
CRC
colorectal cancer
CRF
case report form
CrCL
creatinine clearance
CT
computed tomography 
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
circulating tumor DNA
CTLA-4
cytotoxic T-lymphocyte antigen-4
Ctrough
trough observed plasma concentration
CXCR2
C-X-C chemokine receptor 2
CXCR3
C-X-C chemokine receptor 3
CXCR5
C-X-C chemokine receptor 5
CYP
cytochrome P450
Revised Protocol No.: 06
Date: 05-Dec-2019
146
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
DDI
drug-drug interaction 
DILI
drug induced liver injury
DKD
diabetic kidney disease 
DLT
dose limiting toxicity
DNA
deoxyribonucleic acid
DOR
duration of response
EC50
50% of the maximal response
ECG 
electrocardiogram
ECOG
Eastern Cooperative Oncology Group 
eGFR
estimated glomerular filtration rate 
EGFR
epidermal growth factor receptor 
EOI
end of infusion
EOT
end of treatment
EU
European Union
F
oral bioavailability 
FDA
Food and Drug Administration
FDG
fluorodeoxyglucose
FFPE
formalin-fixed paraffin-embedded 
FOLFIRI
FOL (folinic acid [leucovorin]) F (fluorouracil [5-fluorouracil])
IRI (irinotecan [CAMPTOSAR])
FOLFOX
FOL (folinic acid [leucovorin]) F (fluorouracil [5-fluorouracil])
OX (oxaliplatin [ELOXATIN])
FSH
follicle stimulating hormone 
FU
follow up
Gem
gemcitabine
GEP
gene expression profiling
GFR
glomerular filtration rate 
GI
gastrointestinal
GPCR
G protein-coupled receptor
GPVE
Global Pharmacovigilance and Epidemiology
Revised Protocol No.: 06
Date: 05-Dec-2019
147
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
GTP-JS
guanosine 5’-3-O-[thio]triphosphate
HCG
human chorionic gonadotropin 
HIV
human immunodeficiency virus
HLM
human liver microsomes 
hPBMC
human peripheral blood mononuclear cell
IB
Investigator’s Brochure 
IC50
50% inhibition concentration
IC90
90% inhibition concentration
ICF
informed consent form
IFNJ
interferon gamma
IgG4
immunoglobulin G4
IHC
immunohistochemistry
INFJ
interferon gamma 
IP/IMP
Investigational [Medicinal] Product 
IRB/IEC
institutional review board / independent ethics committee
IRT
Interactive Response Technologies 
IV
intravenous
Kd
dissociation constant 
KI
knock in
LCMS/MS 
liquid chromatography-tandem mass spectrometry 
LDH
lactate dehydrogenase 
M1
metabolite number 1
MATE
multidrug and toxin extrusion protein
MCP-1
monocyte chemotactic protein-1
MDSC
myeloid-derived suppressor cells
MR_AUC(0-24)
ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for 
molecular weight
MR_Cmax
ratio of metabolite Cmax to parent Cmax, corrected for molecular weight
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
Revised Protocol No.: 06
Date: 05-Dec-2019
148
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
MRI
magnetic resonance imaging
MSI-H
microsatellite instability high 
MSS
microsatellite stable 
NCI
National Cancer Institute
NGS
next generation sequencing
NMN
N-methylnicotinamide 
Non-IP/Non-IMP
Non-investigational [Medicinal] Product
NSCLC
nonsmall cell lung cancer 
NTCP
sodium-taurocholate cotransporting polypeptide
OATP
organic anion transporting polypeptide
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
PD
progressive disease
PD-1
programmed death-1 (receptor)
PD-L1
programmed death-ligand 1
PE
physical exam
PEE
probability of early efficacy
PET
positron emission tomography
PET
probability of early termination
PFS
progression free survival
PFSR
progression free survival rate
P-gp
P glycoprotein 
PID
participant identification number
PK
pharmacokinetic(s)
PPK
population PK analysis
PO
by mouth; orally
PR
partial response 
PT
preferred term
Revised Protocol No.: 06
Date: 05-Dec-2019
149
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
Q2W
every 2 weeks
Q4W
every 4 weeks
Q8W
every 8 weeks
Q12W
every 12 weeks
QD
once per day
QTcF
QT corrected for heart rate using Fridericia's method
R&D
research and development
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors 
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SCCHN
squamous cell carcinoma of the head and neck
SD
stable disease
SMT
Safety Management Team
SNP
single nucleotide polymorphism
SOC
system organ class
SUSAR
suspected, unexpected serious adverse reaction
T3
triiodothyronine
T4
thyroxine
TAM
tumor-associated macrophage
TCR
T-cell repertoire / T-cell receptor clonality
TG
thioglycollate
T-HALF
apparent terminal phase half-life
Tmax
time of maximum observed plasma concentration
TME
tumor microenvironment 
Treg
regulatory T cells 
TSH
thyroid stimulating hormone
Revised Protocol No.: 06
Date: 05-Dec-2019
150
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Term
Definition
UGT
uridine 5'-diphospho-glucuronosyltransferase
UGT1A1
5'-diphospho-glucuronosyltransferase 
ULN
upper limit of normal
US
United States
USA
United States of America
VEGF
vascular endothelial growth factor
Vss
volume of distribution at steady state 
Vz
volume of distribution of terminal phase 
WBC
white blood cell
WES
whole-exome sequencing
WOCBP
women of childbearing potential
Revised Protocol No.: 06
Date: 05-Dec-2019
151
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the CRF is intended to refer to a person 
(Participant) who has consented to participate in the clinical research study.
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:
•
Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines Good Clinical Practice (GCP),
•
as defined by the International Council on Harmonisation (ICH)
•
in accordance with the ethical principles underlying European Union Directive 2001/20/EC
•
United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
•
applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc.) that is likely to 
affect, to a significant degree one or more of the following: (1) the physical, safety, or mental 
integrity of 1 or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated date). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant
recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects/participants. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure or 
product labeling information to be provided to subjects/participants and any updates.
Revised Protocol No.: 06
Date: 05-Dec-2019
152
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants.
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant  approval/favorable opinion(s) the deviation or change will be submitted, as 
soon as possible to:
•
IRB/IEC
•
Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and (3) 
the new form must be used to obtain consent from new subjects/participants prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
FINANCIAL DISCLOSURE
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate. 
In situations where consent cannot be given to subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant
volunteers to participate. 
Revised Protocol No.: 06
Date: 05-Dec-2019
153
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki.
Investigators must:
•
Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
•
Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study.
•
Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 
•
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects/participants, prior to the beginning of 
the study, and after any revisions are completed for new information.
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects'/participants’ signed ICF and, in the US, the subjects’/participants’ signed HIPAA 
Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society.
SOURCE DOCUMENTS
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
Revised Protocol No.: 06
Date: 05-Dec-2019
154
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:
•
amount received and placed in storage area
•
amount currently in storage area
•
label identification number or batch number
•
amount dispensed to and returned by each 
participant, including unique participant
identifiers
•
amount transferred to another area/site for 
dispensing or storage
•
nonstudy disposition (e.g., lost, wasted) 
•
amount destroyed at study site, if applicable
•
amount returned to BMS
•
retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 
•
dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form.
Sourced by site, and not supplied by 
BMS or its vendors (examples include IP 
sourced 
from 
the 
sites 
stock or 
The investigator or designee accepts responsibility 
for documenting traceability and study treatment
integrity in accordance with requirements applicable 
Revised Protocol No.: 06
Date: 05-Dec-2019
155
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
If
Then
commercial supply, or a specialty 
pharmacy)
under law and the SOPs/standards of the sourcing 
pharmacy.
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor or designee. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
BMS electronic data capture tool. The investigator must retain a copy of the CRFs including 
records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals
Revised Protocol No.: 06
Date: 05-Dec-2019
156
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
MONITORING
Sponsor or designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents.
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee.
RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee.
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site.
If..
Then
Study treatments supplied by BMS (including 
its vendors
Any unused study treatments supplied by BMS 
can only be destroyed after being inspected and 
reconciled by the responsible Study Monitor 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics).
Revised Protocol No.: 06
Date: 05-Dec-2019
157
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or 
commercial 
supply, 
or 
a 
specialty 
pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:
•
On-site disposal practices must not expose humans to risks from the drug.
•
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
•
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.
•
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.
•
Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
For this study, study treatments (those supplied by BMS or its vendors) such as full or partially 
used study treatment containers, vials, syringes cannot be destroyed on-site.
It is however, the investigator’s or designee’s responsibility to arrange for disposal of all empty 
study treatment containers, provided that procedures for proper disposal have been established 
according to applicable federal, state, local, and institutional guidelines and procedures, and 
provided that appropriate records of disposal are kept. The return of full or partially used study 
treatments supplied by BMS or its vendors will be arranged by the responsible Study Monitor.
Revised Protocol No.: 06
Date: 05-Dec-2019
158
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
CLINICAL STUDY REPORT
A Signatory Investigator must be selected to sign the clinical study report. 
For each CSR related to this protocol, the following criteria will be used to select the signatory 
Investigator:
•
Participant recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
•
Other criteria (as determined by the study team)
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal investigator, sub-investigator or any other member of the study staff without the prior 
written consent of the Sponsor.
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work.
Revised Protocol No.: 06
Date: 05-Dec-2019
159
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
Revised Protocol No.: 06
Date: 05-Dec-2019
160
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation participant administered study treatment 
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. This includes worsening of an 
abnormal baseline result. Note that abnormal lab tests or other safety assessments should 
only be reported as AEs if the final diagnosis is not available. Once the final diagnosis is 
known, the reported term should be updated to be the diagnosis.
•
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even though 
it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose, as a verbatim term (as reported by the 
investigator), should not be reported as an AE/SAE unless it is an intentional overdose taken 
with possible suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae and should specify "intentional overdose" as the verbatim term.
Events NOT Meeting the AE Definition
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
Revised Protocol No.: 06
Date: 05-Dec-2019
161
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SERIOUS ADVERSE EVENTS
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any 
dose:
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
•
a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)
•
elective surgery, planned prior to signing consent
•
admissions as per protocol for a planned medical/surgical procedure
•
routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy)
•
medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases
•
admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)
•
admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols)
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 
Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see section 9.2.5 for reporting pregnancies).
Revised Protocol No.: 06
Date: 05-Dec-2019
162
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Any component of a study endpoint that is considered related to study therapy should be reported 
as SAE (e.g., death is an endpoint, if death occurred due to anaphylaxis, anaphylaxis must be 
reported).
EVALUATING AES AND SAES
Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.
•
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated.
•
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she has
reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.
•
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. (Note: Follow-
up SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
Revised Protocol No.: 06
Date: 05-Dec-2019
163
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
REPORTING OF SAES TO SPONSOR OR DESIGNEE
•
SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event.
•
SAEs must be recorded on the SAE Report Form.
−
The required method for SAE data reporting is through the eCRF.
−
The paper SAE Report Form is only intended as a back-up option when the electronic 
data capture (EDC) system is unavailable /not functioning for transmission of the eCRF 
to BMS (or designee).
♦In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission.
♦When paper forms are used, the original paper forms are to remain on site.
•
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission.
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list
Revised Protocol No.: 06
Date: 05-Dec-2019
164
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP
•
Premenarchal
•
Premenopausal female with 1 of the following:
−
Documented hysterectomy
−
Documented bilateral salpingectomy
−
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
•
Postmenopausal female
−
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. 
•
1 week minimum for vaginal hormonal products (rings, creams, gels)
•
4 week minimum for transdermal products
•
8 week minimum for oral product
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal. 
End of Relevant Systemic Exposure
•
End of relevant systemic exposure is the time point where the IMP or any active major 
metabolites has decreased to a concentration that is no longer considered to be relevant for 
Revised Protocol No.: 06
Date: 05-Dec-2019
165
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
human teratogenicity or fetotoxicity. This should be evaluated in context of safety margins 
from the no-observed adverse effect level (NOAEL) or the time required for 5 half-lives of the 
IMP to pass.
METHODS OF CONTRACEPTION
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of <1% per year when used consistently and correctly.a
•
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b 
−
oral (birth control pills)
−
intravaginal (vaginal birth control suppositories, rings, creams, gels)
−
transdermal 
•
Combined (estrogen- and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy
•
Progestogen-only hormonal contraception associated with inhibition of ovulation (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b 
−
oral 
−
injectable 
•
Progesterone-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User Independent
•
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b
•
Intrauterine device (IUD)
•
Intrauterine hormone-releasing system (IUS) (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol)b,c
•
Bilateral tubal occlusion
•
Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Revised Protocol No.: 06
Date: 05-Dec-2019
166
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
A vasectomy is a highly effective contraception method provided that the participant is the 
sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.
•
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.
•
Continuous abstinence must begin at least 30 days prior to initiation of study therapy
•
It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
•
WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
•
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence 
•
Periodic abstinence (including but not limited to calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study drug, which may 
reduce the efficacy of the contraceptive method.  Hormonal contraception is permissible only 
when there is sufficient evidence that the IMP and other study medications will not alter 
hormonal exposures such that contraception would be ineffective or result in increased 
exposures that could be potentially hazardous.  In this case, alternative methods of 
contraception should be utilized. 
c Intrauterine hormone releasing systems are acceptable methods of contraception in the 
absence of definitive drug interaction studies when hormone exposures from intrauterine 
devices do not alter contraception effectiveness
Revised Protocol No.: 06
Date: 05-Dec-2019
167
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of >1% per year when used consistently and correctly.
•
Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously
•
Diaphragm with spermicide
•
Cervical cap with spermicide
•
Vaginal Sponge with spermicide
•
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited)
Unacceptable Methods of Contraception
•
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
•
Withdrawal (coitus interruptus).
•
Spermicide only
•
Lactation amenorrhea method (LAM)
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S) OF 
CHILD BEARING POTENTIAL.
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to the following during the treatment and until the end of relevant systemic exposure.
•
Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator.
•
Male participants are required to use a condom for study duration and until end of relevant 
systemic exposure defined as 7 months after the end of study treatment.
•
Female partners of males participating in the study to consider use of effective methods of 
contraception until the end of relevant systemic exposure, defined as 7 months after the end of 
treatment in the male participant.
•
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile vaginal intercourse or use a male condom during each episode of penile penetration 
during the treatment and until 7 months after the end of study treatment.
•
Refrain from donating sperm for the duration of the study treatment and until 7 months after 
the end of study treatment.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting
Revised Protocol No.: 06
Date: 05-Dec-2019
168
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 5
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS
1
EVALUATION OF LESIONS
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST 1.1) guideline with BMS modifications.1
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows:
1.1
Measurable
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of:
10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ൒2x slice thickness if 
greater than 5mm.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be t 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm).
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
t 15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis t 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
1.2
Non-Measurable
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10mm or pathological lymph nodes with t 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
Revised Protocol No.: 06
Date: 05-Dec-2019
169
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
1.3
Special considerations regarding lesion measurability
1.3.1
Bone lesions
•
Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
•
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.
•
Blastic bone lesions are non-measurable.
1.4
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded).
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of 
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’).
Revised Protocol No.: 06
Date: 05-Dec-2019
170
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
2.
RESPONSE CRITERIA
2.1
Evaluation of Target Lesions
•
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.
•
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters.
•
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression).
•
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
•
Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above.
2.1.1
Special Notes on the Assessment of Target Lesions
2.1.1.1
Lymph nodes
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions.
2.1.1.2
Target lesions that become ‘too small to measure’
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
Revised Protocol No.: 06
Date: 05-Dec-2019
171
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm.
2.1.1.3
Lesions that split or coalesce on treatment
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’.
2.2
Evaluation of Non-Target Lesions
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol.
•
Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10mm short axis). 
•
Non-CR/Non-PD: Persistence of one or more non-target lesion(s)
•
Progressive Disease (PD): Unequivocal progression of existing non-target lesions.
2.2.1
Special Notes on Assessment of Progression of Non-Target Disease
The concept of progression of non-target disease requires additional explanation as follows:
2.2.1.1
When the patient also has measurable disease
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare.
2.2.1.2
When the patient has only non-measurable disease
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
Revised Protocol No.: 06
Date: 05-Dec-2019
172
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore the increase must be substantial.
2.2.2
New Lesions
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of 
new radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought 
to represent something other than tumor (for example, some ‘new’ bone lesions may be simply 
healing or flare of pre-existing lesions). This is particularly important when the patient’s baseline 
lesions show partial or complete response. For example, necrosis of a liver lesion may be reported 
on a CT scan report as a ‘new’ cystic lesion, which it is not.
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD).
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm:
1. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
2. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
Revised Protocol No.: 06
Date: 05-Dec-2019
173
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD.
2.3
Response Assessment
2.3.1
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmation and censoring rules regarding subsequent therapy. The patient’s best overall response 
assignment will depend on the findings of both target and non-target disease and will also take into 
consideration the appearance of new lesions. Furthermore, depending on the nature of the study 
and the protocol requirements, it may also require confirmatory measurement.
2.3.2
Time Point Response
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 2.3.2-2 is to be used. 
Table 2.3.2-1:
Time Point Response: Patients With Target (± Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all 
evaluated
No
PR
SD
Non-PD or not all 
evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable
Table 2.3.2-2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Revised Protocol No.: 06
Date: 05-Dec-2019
174
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2.3.2-2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response, PD = progressive disease and NE = inevaluable
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
2.3.3
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
≥4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 2.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment or randomization date.
For example, if the first scheduled follow-up imaging visit is Week 6 (± 7 days) for a particular 
protocol, a Best Response of SD can only be made after the subject is on-study for a minimum of 
6 weeks (42 days) minus 7 days, for an absolute minimum time on-study of 35 days from the 
reference start date (reference date is considered Day 1 on study).  If the subject is not on-study 
for at least this amount of time, any tumor assessment indicating stable disease before this time 
period will have a Best Response of NE unless PD is identified.
Special note on response assessment: When nodal disease is included in the sum of target lesions 
and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a measurement reported 
on scans. This measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. As noted earlier, this 
means that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF).
Table 2.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
Revised Protocol No.: 06
Date: 05-Dec-2019
175
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
PR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE = inevaluable
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR.
2.3.4
Confirmation Scans
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation.
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease.
REFERENCES
1 Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors:
revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.
Revised Protocol No.: 06
Date: 05-Dec-2019
176
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 6
MANAGEMENT ALGORITHMS
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens.
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated.
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with low-
grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account when 
switching to the equivalent dose of oral corticosteroids.
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended.
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used.
Revised Protocol No.: 06
Date: 05-Dec-2019
177
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
178
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
179
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
180
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
181
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
182
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
183
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
184
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Revised Protocol No.: 06
Date: 05-Dec-2019
185
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 7
ECOG PERFORMANCE STATUS SCALE
STATUS
ECOG SCALE
Normal activity
0
Symptoms, but fully ambulatory
1
Symptomatic, but in bed < 50% of the day.
2
Needs to be in bed > 50% of the day, but not bedridden
3
Unable to get out of bed
4
Dead
5
Revised Protocol No.: 06
Date: 05-Dec-2019
186
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 8
CYP3A4 AND P-GP GUIDANCE
The lists below are not meant to be all inclusive. Please consult individual drug labels for further 
information. Additional information is also available at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling/ucm093664.htm
Table 1:
Classification of In Vivo Inhibitors of CYP Enzymes
CYP Enzymes
Strong Inhibitorsa
≥ 5-fold Increase in AUC
or > 80% Decrease in CL
Moderate Inhibitorsb
≥ 2 but < 5-fold Increase in 
AUC or 50-80% Decrease 
in CL
Weak Inhibitorsc
≥ 1.25 but < 2-fold 
Increase in AUC or
20-50% Decrease in CL
CYP3A
Boceprevir, clarithromycin, 
conivaptan, grapefruit 
juice,d indinavir, 
itraconazole, ketoconazole,
lopinavir/ritonavir,
mibefradil,e nefazodone, 
nelfinavir, posaconazole, 
ritonavir, saquinavir,
telaprevir, telithromycin,
voriconazole
Amprenavir, aprepitant,
atazanavir, ciprofloxacin,
darunavir/ritonavir, 
diltiazem, erythromycin, 
fluconazole, fosamprenavir, 
grapefruit juice,d imatinib, 
verapamil
Alprazolam, amiodarone, 
amlodipine, atorvastatin, 
bicalutamide, cilostazol, 
cimetidine, cyclosporine, 
fluoxetine, fluvoxamine, 
ginkgo,f goldenseal,f
isoniazid, nilotinib, oral 
contraceptives, ranitidine, 
ranolazine,
tipranavir/ritonavir, zileuton
Please note that this is not an exhaustive list.
a A strong inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a substrate for that CYP 
by equal or more than 5-fold.
b A moderate inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate 
for that CYP by less than 5-fold but equal to or more than 2-fold.
c A weak inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate for 
that CYP by less than 2-fold but equal to or more than 5-fold.
d The effect of grapefruit juice varies widely among brands and is concentration, dose, and preparation dependent. 
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used 
(eg, high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (eg, low 
dose, single strength).
e Withdrawn from the United States market because of safety reasons.
f Herbal product.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
Revised Protocol No.: 06
Date: 05-Dec-2019
187
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Table 2:
Classification of In Vivo Inducers of CYP Enzymes
CYP Enzymes
Strong Inducers
≥ 80% Decrease in AUC
Moderate Inducers
50-80% Decrease in AUC
Weak Inducers
20-50% Decrease in AUC
CYP3A
Avasimibe,a carbamazepine, 
phenytoin, rifampin, St. 
John’s wortb
Bosentan, efavirenz, 
etravirine, modafinil, 
nafcillin
Amprenavir, aprepitant, 
armodafinil, echinacea,c
pioglitazone, prednisone, 
rufinamide
Please note that this is not an exhaustive list.
a Not a marketed drug.
b The effect of St. John’s wort varies widely and is preparation dependent.
c Herbal product.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
Table 3:
Examples of clinical inhibitors for transporters
Transporter
Inhibitors
≥2 fold increase in digoxin AUC with co-administration 
P-gp
Amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, lopinavir 
and ritonavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, verapamil
Please note that this is not an exhaustive list.
Abbreviations: AUC = area under the concentration-time curve
Revised Protocol No.: 06
Date: 05-Dec-2019
188
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 9
MATE INHIBITORS GUIDANCE
The list below is not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Table 1:
Examples of clinical inhibitors for MATE
Transporter
Inhibitors
MATE
Cimetidine, famotidine, cetirizine, cephalexin, cephradine,imatinib, indinavir, 
ritonavir,ondansetron, pyrimethamine, mitoxantron, topotecan,zafirlukast, 
corticosterone, chlorpheniramine,dasatinib, 
erlotinib,nilotinib,disopyramide,procainamide,diphenylhydramine,desipramine,imipra
mine,diltiazem, quinidine, verapamil, metformin, pramipexol, talipexol, 
ranitidine,trimethoprim
Please note that this is not an exhaustive list.
Revised Protocol No.: 06
Date: 05-Dec-2019
189
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 10
UGT1A1 GUIDANCE
The list below is not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Table 1:
Examples of clinical inhibitors for UGT1A1
Transporter
Inhibitors
UGT1A1
atazanavir, gemfibrozil and indinavir, ketoconazole, diclofenac, probenecid, silibinin, 
tacrolimus
Please note that this is not an exhaustive list.
Revised Protocol No.: 06
Date: 05-Dec-2019
190
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 11
MATE SUBSTRATES GUIDANCE
The list below is not meant to be all inclusive. Please consult individual drug labels for further 
information. 
Table 1:
Examples of clinical substrates for MATE
Transporter
substrates
MATE
Metformin, cisplatin, oxaliplatin, ganciclovir, acyclovir, procainamide, captopril, 
quinine
Please note that this is not an exhaustive list.
Revised Protocol No.: 06
Date: 05-Dec-2019
191
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 12
CORE AND EXTENDED ADME GENE LIST
Core ADME Gene List:
Gene 
Symbol
Full Gene Name
Class
ABCB1
ATP-binding cassette, sub-family B (MDR/TAP), member 1
Transporter
ABCC2
ATP-binding cassette, sub-family C (CFTR/MRP), member 2
Transporter
ABCG2
ATP-binding cassette, sub-family G (WHITE), member 2
Transporter
CYP1A1
cytochrome P450, family 1, subfamily A, polypeptide 1
Phase I
CYP1A2
cytochrome P450, family 1, subfamily A, polypeptide 2
Phase I
CYP2A6
cytochrome P450, family 2, subfamily A, polypeptide 6
Phase I
CYP2B6
cytochrome P450, family 2, subfamily B, polypeptide 6
Phase I
CYP2C19
cytochrome P450, family 2, subfamily C, polypeptide 19
Phase I
CYP2C8
cytochrome P450, family 2, subfamily C, polypeptide 8
Phase I
CYP2C9
cytochrome P450, family 2, subfamily C, polypeptide 9
Phase I
CYP2D6
cytochrome P450, family 2, subfamily D, polypeptide 6
Phase I
CYP2E1
cytochrome P450, family 2, subfamily E, polypeptide 1
Phase I
CYP3A4
cytochrome P450, family 3, subfamily A, polypeptide 4
Phase I
CYP3A5
cytochrome P450, family 3, subfamily A, polypeptide 5
Phase I
DPYD
dihydropyrimidine dehydrogenase
Phase I
GSTM1
glutathione S-transferase M1
Phase II
GSTP1
glutathione S-transferase pi
Phase II
GSTT1
glutathione S-transferase theta 1
Phase II
NAT1
N-acetyltransferase 1 (arylamine N-acetyltransferase)
Phase II
NAT2
N-acetyltransferase 2 (arylamine N-acetyltransferase)
Phase II
SLC15A2
solute carrier family 15 (H+/peptide transporter), member 2
Transporter
SLC22A1
solute carrier family 22 (organic cation transporter), member 1
Transporter
SLC22A2
solute carrier family 22 (organic cation transporter), member 2
Transporter
SLC22A6
solute carrier family 22 (organic anion transporter), member 6
Transporter
SLCO1B1
solute carrier organic anion transporter family, member 1B1
Transporter
SLCO1B3
solute carrier organic anion transporter family, member 1B3
Transporter
SULT1A1
sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1
Phase II
TPMT
thiopurine S-methyltransferase,
Phase II
UGT1A1
UDP glucuronosyltransferase 1 family, polypeptide A1
Phase II
UGT2B15
UDP glucuronosyltransferase 2 family, polypeptide B15
Phase II
UGT2B17
UDP glucuronosyltransferase 2 family, polypeptide B17
Phase II
UGT2B7
UDP glucuronosyltransferase 2 family, polypeptide B7
Phase II
Revised Protocol No.: 06
Date: 05-Dec-2019
192
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Extended ADME Gene List:
Gene Symbol
Full Gene Name
Class
ABCB8
ATP-binding cassette, sub-family B (MDR/TAP), member 8
Transporter
ABCC12
ATP-binding cassette, sub-family C (CFTR/MRP), member 
12
Transporter
ABCC3
ATP-binding cassette, sub-family C (CFTR/MRP), member 
3
Transporter
ABCC4
ATP-binding cassette, sub-family C (CFTR/MRP), member 
4
Transporter
AHR
aryl hydrocarbon receptor
Modifier
ALDH4A1
aldehyde dehydrogenase 4 family, member A1
Phase I
ALDH5A1
aldehyde dehydrogenase 5 family, member A1
Phase I
ALDH6A1
aldehyde dehydrogenase 6 family, member A1
Phase I
CES1
carboxylesterase 1 (monocyte/macrophage serine 
esterase 1)
Phase I
CES2
carboxylesterase 2 (intestine, liver)
Phase I
CYP7A1
cytochrome P450, family 7, subfamily A, polypeptide 1
Phase I
EPHX1
epoxide hydrolase 1, microsomal (xenobiotic)
Phase I
FMO3
flavin containing monooxygenase 3
Phase I
GSTA1
glutathione S-transferase A1
Phase II
GSTA2
glutathione S-transferase A2
Phase II
GSTA3
glutathione S-transferase A3
Phase II
GSTA4
glutathione S-transferase A4
Phase II
GSTA5
glutathione S-transferase A5
Phase II
Revised Protocol No.: 06
Date: 05-Dec-2019
193
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
GSTM2
glutathione S-transferase M2 (muscle),glutathione S-
transferase M4
Phase II
GSTM3
glutathione S-transferase M3 (brain)
Phase II
GSTM4
glutathione S-transferase M4
Phase II
GSTO1
glutathione S-transferase omega 1,glutathione S-
transferase omega 2
Phase II
GSTO2
glutathione S-transferase omega 2
Phase II
GSTT2
glutathione S-transferase theta 2
Phase II
SLC10A1
solute carrier family 10 (sodium/bile acid cotransporter 
family), member 1
Transporter
SLC15A1
solute carrier family 15 (oligopeptide transporter), member 
1
Transporter
SLC22A11
solute carrier family 22 (organic anion/cation transporter), 
member 11
Transporter
SLC22A8
solute carrier family 22 (organic anion transporter), 
member 8
Transporter
SLC7A5
solute carrier family 7 (cationic amino acid transporter, y+ 
system), member 5
Transporter
SLCO1A2
solute carrier organic anion transporter family, member 
1A2
Transporter
SLCO2B1
solute carrier organic anion transporter family, member 
2B1
Transporter
SULT1A2
sulfotransferase family, cytosolic, 1A, phenol-preferring, 
member 2
Phase II
SULT1A3
sulfotransferase family, cytosolic, 1A, phenol-preferring, 
member 3
Phase II
SULT1B1
sulfotransferase family, cytosolic, 1B, member 1
Phase II
UGT1A3
UDP glucuronosyltransferase 1 family, polypeptide A3
Phase II
UGT1A6
UDP glucuronosyltransferase 1 family, polypeptide A6
Phase II
UGT1A7
UDP glucuronosyltransferase 1 family, polypeptide A7
Phase II
Revised Protocol No.: 06
Date: 05-Dec-2019
194
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
UGT1A8
UDP glucuronosyltransferase 1 family, polypeptide A8
Phase II
UGT1A9
UDP glucuronosyltransferase 1 family, polypeptide A9
Phase II
UGT2A1
UDP glucuronosyltransferase 2 family, polypeptide A1
Phase II
UGT2B11
UDP glucuronosyltransferase 2 family, polypeptide B11
Phase II
UGT2B28
UDP glucuronosyltransferase 2 family, polypeptide B28
Phase II
UGT2B4
UDP glucuronosyltransferase 2 family, polypeptide B4
Phase II
ABCA1
ATP-binding cassette, sub-family A (ABC1), member 1
Transporter
ABCA4
ATP-binding cassette, sub-family A (ABC1), member 4
Transporter
ABCB11
ATP-binding cassette, sub-family B (MDR/TAP), member 
11
Transporter
ABCB4
ATP-binding cassette, sub-family B (MDR/TAP), member 4
Transporter
ABCB5
ATP-binding cassette, sub-family B (MDR/TAP), member 5
Transporter
ABCB6
ATP-binding cassette, sub-family B (MDR/TAP), member 6
Transporter
ABCB7
ATP-binding cassette, sub-family B (MDR/TAP), member 7
Transporter
ABCC1
ATP-binding cassette, sub-family C (CFTR/MRP), member 
1
Transporter
ABCC10
ATP-binding cassette, sub-family C (CFTR/MRP), member 
10
Transporter
ABCC11
ATP-binding cassette, sub-family C (CFTR/MRP), member 
11
Transporter
ABCC5
ATP-binding cassette, sub-family C (CFTR/MRP), member 
5
Transporter
ABCC6
ATP-binding cassette, sub-family C (CFTR/MRP), member 
6
Transporter
ABCC8
ATP-binding cassette, sub-family C (CFTR/MRP), member 
8
Transporter
Revised Protocol No.: 06
Date: 05-Dec-2019
195
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
ABCC9
ATP-binding cassette, sub-family C (CFTR/MRP), member 
9
Transporter
ABCG1
ATP-binding cassette, sub-family G (WHITE), member 1
Transporter
ADH1A
alcohol dehydrogenase 1A (class I), alpha polypeptide
Phase I
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide
Phase I
ADH1C
alcohol dehydrogenase 1C (class I), gamma polypeptide
Phase I
ADH4
alcohol dehydrogenase 4 (class II), pi polypeptide
Phase I
ADH5
alcohol dehydrogenase 5 (class III), chi 
polypeptide,methionyl aminopeptidase 1
Phase I
ADH6
alcohol dehydrogenase 6 (class V)
Phase I
ADH7
alcohol dehydrogenase 7 (class IV), mu or sigma 
polypeptide
Phase I
ALDH1A1
aldehyde dehydrogenase 1 family, member A1
Phase I
ALDH1A2
aldehyde dehydrogenase 1 family, member A2
Phase I
ALDH1A3
aldehyde dehydrogenase 1 family, member A3
Phase I
ALDH1B1
aldehyde dehydrogenase 1 family, member B1
Phase I
ALDH2
aldehyde dehydrogenase 2 family (mitochondrial)
Phase I
ALDH3A1
aldehyde dehydrogenase 3 family, memberA1
Phase I
ALDH3A2
aldehyde dehydrogenase 3 family, member A2
Phase I
ALDH3B1
aldehyde dehydrogenase 3 family, member B1
Phase I
ALDH3B2
aldehyde dehydrogenase 3 family, member B2
Phase I
ALDH7A1
aldehyde dehydrogenase 7 family, member A1
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
196
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
ALDH8A1
aldehyde dehydrogenase 8 family, member A1
Phase I
ALDH9A1
aldehyde dehydrogenase 9 family, member A1
Phase I
AOX1
aldehyde oxidase 1
Phase I
ARNT
aryl hydrocarbon receptor nuclear translocator
Modifier
CBR1
carbonyl reductase 1
Phase I
CBR3
carbonyl reductase 3
Phase I
CDA
cytidine deaminase
Modifier
CYB5R3
cytochrome b5 reductase 3
Phase I
CYP11A1
cytochrome P450, family 11, subfamily A, polypeptide 1
Phase I
CYP11B1
cytochrome P450, family 11, subfamily B, polypeptide 1
Phase I
CYP11B2
cytochrome P450, family 11, subfamily B, polypeptide 2
Phase I
CYP17A1
cytochrome P450, family 17, subfamily A, polypeptide 1
Phase I
CYP1B1
cytochrome P450, family 1, subfamily B, polypeptide 1
Phase I
CYP20A1
cytochrome P450, family 20, subfamily A, polypeptide 1
Phase I
CYP20A1
cytochrome P450, family 20, subfamily A, polypeptide 1
Phase I
CYP21A2
cytochrome P450, family 21, subfamily A, polypeptide 2
Phase I
CYP24A1
cytochrome P450, family 24, subfamily A, polypeptide 1
Phase I
CYP26A1
cytochrome P450, family 26, subfamily A, polypeptide 1
Phase I
CYP27A1
cytochrome P450, family 27, subfamily A, polypeptide 1
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
197
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
CYP2A13
cytochrome P450, family 2, subfamily A, polypeptide 13
Phase I
CYP2A7
cytochrome P450, family 2, subfamily A, polypeptide 7
Phase I
CYP2C18
cytochrome P450, family 2, subfamily C, polypeptide 18
Phase I
CYP2F1
cytochrome P450, family 2, subfamily F, polypeptide 1
Phase I
CYP2J2
cytochrome P450, family 2, subfamily J, polypeptide 2
Phase I
CYP39A1
cytochrome P450, family 39, subfamily A, polypeptide 1
Phase I
CYP3A43
cytochrome P450, family 3, subfamily A, polypeptide 43
Phase I
CYP3A7
cytochrome P450, family 3, subfamily A, polypeptide 7
Phase I
CYP4B1
cytochrome P450, family 4, subfamily B, polypeptide 1
Phase I
CYP4F11
cytochrome P450, family 4, subfamily F, polypeptide 11
Phase I
CYP51A1
cytochrome P450, family 51, subfamily A, polypeptide 1
Phase I
EPHX2
epoxide hydrolase 2, cytoplasmic
Phase I
FMO1
flavin containing monooxygenase 1
Phase I
FMO2
flavin containing monooxygenase 2
Phase I
FMO4
flavin containing monooxygenase 4
Phase I
FMO5
flavin containing monooxygenase 5
Phase I
GPX2
glutathione peroxidase 2 (gastrointestinal)
Phase I
GPX3
glutathione peroxidase 3 (plasma)
Phase I
GPX7
glutathione peroxidase 7
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
198
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
GSR
glutathione reductase
Phase I
GSTK1
glutathione S-transferase kappa 1
Phase II
GSTM5
glutathione S-transferase M5
Phase II
GSTZ1
glutathione transferase zeta 1 (maleylacetoacetate 
isomerase)
Phase II
NNMT
nicotinamide N-methyltransferase
Phase II
NR1I2
nuclear receptor subfamily 1, group I, member 2
Modifier
NR1I3
nuclear receptor subfamily 1, group I, member 3
Modifier
PNMT
phenylethanolamine N-methyltransferase
Phase II
PON1
paraoxonase 1
Phase I
PON2
paraoxonase 2
Phase I
PON3
paraoxonase 3
Phase I
POR
P450 (cytochrome) oxidoreductase
Modifier
PPARD
peroxisome proliferative activated receptor, delta
Modifier
PPARG
peroxisome proliferative activated receptor, gamma
Modifier
RXRA
retinoid X receptor, alpha
Modifier
SLC10A2
solute carrier family 10 (sodium/bile acid cotransporter 
family), member 2
Transporter
SLC13A1
solute carrier family 13 (sodium/sulfate symporters), 
member 1
Transporter
SLC13A2
solute carrier family 13 (sodium-dependent dicarboxylate 
transporter), member 2
Transporter
SLC13A3
solute carrier family 13 (sodium-dependent dicarboxylate 
transporter), member 3
Transporter
Revised Protocol No.: 06
Date: 05-Dec-2019
199
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
SLC16A1
solute carrier family 16 (monocarboxylic acid Transporter), 
member 1
Transporter
SLC19A1
solute carrier family 19 (folate transporter), member 1
Transporter
SLC22A10
solute carrier family 22 (organic anion/cation transporter), 
member 10
Transporter
SLC22A12
solute carrier family 22 (organic anion/cation transporter), 
member 12
Transporter
SLC22A13
solute carrier family 22 (organic cation transporter), 
member 13
Transporter
SLC22A14
solute carrier family 22 (organic cation transporter), 
member 14
Transporter
SLC22A15
solute carrier family 22 (organic cation transporter), 
member 15
Transporter
SLC22A16
solute carrier family 22 (organic cation transporter), 
member 16
Transporter
SLC22A17
solute carrier family 22 (organic cation transporter), 
member 17
Transporter
SLC22A18
solute carrier family 22 (organic cation transporter), 
member 18
Transporter
SLC22A18AS
solute carrier family 22 (organic cation transporter), 
member 18 antisense
Transporter
SLC22A3
solute carrier family 22 (extraneuronal monoamine 
transporter), member 3
Transporter
SLC22A4
solute carrier family 22 (organic cation transporter), 
member 4
Transporter
SLC22A5
solute carrier family 22 (organic cation transporter), 
member 5
Transporter
SLC22A7
solute carrier family 22 (organic anion transporter), 
member 7
Transporter
SLC22A9
solute carrier family 22 (organic anion/cation transporter), 
member 9
Transporter
SLC27A1
solute carrier family 27 (fatty acid transporter), member 1
Transporter
SLC28A1
solute carrier family 28 (sodium-coupled nucleoside 
transporter), member 1
Transporter
SLC28A2
solute carrier family 28 (sodium-coupled nucleoside 
transporter), member 2
Transporter
Revised Protocol No.: 06
Date: 05-Dec-2019
200
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
SLC28A3
solute carrier family 28 (sodium-coupled nucleoside 
transporter), member 3
Transporter
SLC29A1
solute carrier family 29 (nucleoside Transporter), member 
1
Transporter
SLC29A2
solute carrier family 29 (nucleoside Transporter), member 
2
Transporter
SLC2A4
solute carrier family 2 (facilitated glucose transporter), 
member 4
Transporter
SLC2A5
solute carrier family 2 (facilitated glucose/fructose 
transporter), member 5
Transporter
SLC5A6
solute carrier family 5 (sodium-dependent vitamin 
transporter)
Transporter
SLC6A6
solute carrier family 6 (neurotransmitter transporter, 
taurine), member 6
Transporter
SLC7A8
solute carrier family 7 (cationic amino acid transporter, y+ 
system), member 8
Transporter
SLCO1C1
solute carrier organic anion transporter family, member 
1C1
Transporter
SLCO2A1
solute carrier organic anion transporter family, member 
2A1
Transporter
SLCO3A1
solute carrier organic anion transporter family, member 
3A1
Transporter
SLCO4A1
solute carrier organic anion transporter family, member 
4A1
Transporter
SLCO4C1
solute carrier organic anion transporter family, member 
4C1
Transporter
SLCO5A1
solute carrier organic anion transporter family, member 
5A1
Transporter
SLCO6A1
solute carrier organic anion transporter family, member 
6A1
Transporter
SULT1C1
sulfotransferase family, cytosolic, 1C, member 1
Phase II
SULT1C2
sulfotransferase family, cytosolic, 1C, member 2
Phase II
SULT1E1
sulfotransferase family 1E, estrogen-preferring, member 1
Phase II
SULT2A1
sulfotransferase family, cytosolic, 2A, DHEA preferring, 
member 1
Phase II
Revised Protocol No.: 06
Date: 05-Dec-2019
201
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
SULT2B1
sulfotransferase family, cytosolic, 2B, member 1
Phase II
TAP1
transporter 1, ATP-binding cassette, sub-family B 
(MDR/TAP)
Transporter
UGT1A10
UDP glucuronosyltransferase 1 family, polypeptide A10
Phase II
UGT1A4
UDP glucuronosyltransferase 1 family, polypeptide A4
Phase II
UGT1A5
UDP glucuronosyltransferase 1 family, polypeptide A5
Phase II
UGT2B10
UDP glucuronosyltransferase 2 family, polypeptide B10
Phase II
ABCC13
ATP-binding cassette, sub-family C (CFTR/MRP), member 
13
Transporter
ARSA
arylsulfatase A
Modifier
CAT
catalase
Modifier
CHST8
carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 
8
Phase II
CYP19A1
cytochrome P450, family 19, subfamily A, polypeptide 1
Phase I
CYP26C1
cytochrome P450, family 26, subfamily C, polypeptide 1
Phase I
CYP27B1
cytochrome P450, family 27, subfamily B, polypeptide 1
Phase I
CYP2R1
cytochrome P450, family 2, subfamily R, polypeptide 1
Phase I
CYP2S1
cytochrome P450, family 2, subfamily S, polypeptide 1
Phase I
CYP46A1
cytochrome P450, family 46, subfamily A, polypeptide 1
Phase I
CYP4A11
cytochrome P450, family 4, subfamily A, polypeptide 11
Phase I
CYP4F12
cytochrome P450, family 4, subfamily F, polypeptide 12
Phase I
CYP4F2
cytochrome P450, family 4, subfamily F, polypeptide 2
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
202
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
CYP4F3
cytochrome P450, family 4, subfamily F, polypeptide 3
Phase I
CYP4F8
cytochrome P450, family 4, subfamily F, polypeptide 8
Phase I
CYP4Z1
cytochrome P450, family 4, subfamily Z, polypeptide 1
Phase I
CYP7B1
cytochrome P450, family 7, subfamily B, polypeptide 1
Phase I
CYP8B1
cytochrome P450, family 8, subfamily B, polypeptide 1
Phase I
DHRS13
dehydrogenase/reductase (SDR family) member 13
Phase I
DHRS2
dehydrogenase/reductase (SDR family) member 2
Phase I
GPX1
glutathione peroxidase 1
Phase I
GPX4
glutathione peroxidase 4 (phospholipid hydroperoxidase)
Phase I
GPX5
glutathione peroxidase 5 (epididymal androgen-related 
protein)
Phase I
GPX6
glutathione peroxidase 6 (olfactory)
Phase I
GSS
glutathione synthetase
Phase I
GSTCD
glutathione S-transferase, C-terminal domain containing
Phase II
HNF4A
hepatocyte nuclear factor 4, alpha
Modifier
HNMT
histamine N-methyltransferase
Phase II
HSD11B1
hydroxysteroid (17-beta) dehydrogenase 11
Phase I
HSD17B11
hydroxysteroid (17-beta) dehydrogenase 11
Phase I
HSD17B14
hydroxysteroid (17-beta) dehydrogenase 14
Phase I
LOC731356
similar to dehydrogenase/reductase (SDR family) member 
4 like 2
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
203
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
MGST1
microsomal glutathione S-transferase 1
Phase II
MGST2
microsomal glutathione S-transferase 2
Phase II
MGST3
microsomal glutathione S-transferase 3
Phase II
MPO
myeloperoxidase
Modifier
NOS1
nitric oxide synthase 1 (neuronal)
Phase I
NOS2A
nitric oxide synthase 2A (inducible, hepatocytes)
Phase I
NOS3
nitric oxide synthase 3 (endothelial cell)
Phase I
PPARA
peroxisome proliferator-activated receptor alpha
Modifier
SERPINA7
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, 
antitrypsin), member 7
Modifier
SLC7A7
solute carrier family 7 (cationic amino acid transporter, y+ 
system), member 7
Transporter
SOD1
superoxide dismutase 1, soluble (amyotrophic lateral 
sclerosis 1 (adult))
Modifier
SOD2
superoxide dismutase 2, mitochondrial
Modifier
SOD3
superoxide dismutase 3, extracellular precursor
Modifier
SULF1
sulfatase 1
Phase I
SULT4A1
sulfotransferase family 4A, member 1
Phase II
TAP2
transporter 2, ATP-binding cassette, sub-family B 
(MDR/TAP)
Transporter
UGT8
UDP glycosyltransferase 8 (UDP-galactose ceramide 
galactosyltransferase)
Phase II
XDH
xanthine dehydrogenase
Phase I
ADHFE1
alcohol dehydrogenase, iron containing, 1
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
204
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
CHST1
carbohydrate (keratan sulfate Gal-6) sulfotransferase 1
Phase II
CHST10
carbohydrate sulfotransferase 10
Phase II
CHST11
carbohydrate (chondroitin 4) sulfotransferase 11
Phase II
CHST12
carbohydrate (chondroitin 4) sulfotransferase 12
Phase II
CHST13
carbohydrate (chondroitin 4) sulfotransferase 13
Phase II
CHST2
carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 
2
Phase II
CHST3
carbohydrate (chondroitin 6) sulfotransferase 3
Phase II
CHST4
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 
4
Phase II
CHST5
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 
5
Phase II
CHST6
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 
6
Phase II
CHST7
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 
7
Phase II
CHST9
carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 
9
Phase II
CYP2D7P1
cytochrome P450, family 2, subfamily D, polypeptide 7 
pseudogene 1
Phase I
DDO
D-aspartate oxidase
Phase I
DHRS1
dehydrogenase/reductase (SDR family) member 1
Phase I
DHRS12
dehydrogenase/reductase (SDR family) member 12
Phase I
DHRS3
dehydrogenase/reductase (SDR family) member 3
Phase I
DHRS4
dehydrogenase/reductase (SDR family) member 4
Phase I
DHRS4L1
dehydrogenase/reductase (SDR family) member 4 like 1
Phase I
Revised Protocol No.: 06
Date: 05-Dec-2019
205
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
DHRS4L2
dehydrogenase/reductase (SDR family) member 4 like 2
Phase I
DHRS7
dehydrogenase/reductase (SDR family) member 7
Phase I
DHRS7B
dehydrogenase/reductase (SDR family) member 7B
Phase I
DHRS7C
dehydrogenase/reductase (SDR family) member 7C
Phase I
DHRS9
dehydrogenase/reductase (SDR family) member 9
Phase I
DHRSX
dehydrogenase/reductase (SDR family) X-linked
Phase I
DPEP1
dipeptidase 1 (renal)
Phase I
FMO6P
flavin containing monooxygenase 6
Phase I
HAGH
hydroxyacylglutathione hydrolase
Phase I
IAPP
islet amyloid polypeptide
Modifier
KCNJ11
potassium inwardly-rectifying channel, subfamily J, 
member 11
Modifier
LOC728667
similar to dehydrogenase/reductase (SDR family) member 
2 isoform 1
Phase I
LOC731931
similar to dehydrogenase/reductase (SDR family) member 
2 isoform 1
Phase I
MAT1A
methionine adenosyltransferase I, alpha
Modifier
METAP1
methionyl aminopeptidase 1
Phase I
PDE3A
phosphodiesterase 3A, cGMP-inhibited
Phase I
PDE3B
phosphodiesterase 3B, cGMP-inhibited
Phase I
PLGLB1
plasminogen-like B1
Phase I
ATP7A
ATPase, Cu++ transporting, alpha polypeptide (Menkes 
syndrome)
Modifier
Revised Protocol No.: 06
Date: 05-Dec-2019
206
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Gene Symbol
Full Gene Name
Class
ATP7B
ATPase, Cu++ transporting, beta polypeptide
Modifier
CFTR
cystic fibrosis transmembrane conductance regulator 
Modifier
Revised Protocol No.: 06
Date: 05-Dec-2019
207
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
APPENDIX 13
REVISED PROTOCOL SUMMARY OF CHANGE HISTORY
Overall Rationale for the Revised Protocol 05, 12-Dec-2019
The revised protocol incorporates additional clarity regarding the recommended dose of 
BMS-813160 used for Part 2 of the study, adds 75-mg and 300-mg BMS-813160 tablets to the 
study formulary, adds exclusions and restrictions on participants receiving live / attenuated 
vaccines, adds clinical guidance on the treatment of treatment-related infusion reactions, and 
provides updates to Appendix 2, Appendix 3, and Appendix 6.
Summary of key changes for Revised Protocol 05
Section Number
& Title
Description of Change
Brief Rationale
Title Page;
1: Synopsis
Short Title added.
Short Title added for clarity and alignment with 
Short Title provided on ClinicalTrials.gov.
1: Synopsis;
3.3: Benefit/Risk 
Assessment;
5.1: Overall Design;
5.1.3: Treatment 
Period (Part 2);
7.2: Method of 
Treatment 
Assignment
Statements related to a BMS-813160 
dose found to be safe in Part 1 were 
replaced with a dose of BMS-813160 
300 mg BID. 
The dose and schedule of BMS-813160 
in Part 2 of the study was clarified as 
300 mg BID, except for Cohort 1b 
(150 mg QD).
Clarification of the dose and schedule of 
BMS-813160 in Part 2 of the study.
1: Synopsis;
5.1: Overall Design
The study design schematic (Part 2) of 
the combination therapy expansion, 
illustrated in Figure 1-2 and 
Figure 5.1-2, was modified to clearly 
state the recommended doses and 
schedules of BMS-813160.
Clarification of the dose and schedule of 
BMS-813160 in Part 2 of the study.
1: Synopsis;
5.1.3: Treatment 
Period (Part 2)
Treatment Period (Part 2) statements 
modified to be read as: “The doses of 
BMS-813160 in Part 2 were chosen 
based on safety, PK, and PD available 
data from Part 1 of the study. Based on 
these considerations, BMS-813160 
300 mg BID dosing regimen was 
selected for primary investigation in 
this study. A regimen of 
BMS-813160 150 mg QD in 
combination with FOLFIRI will also 
be evaluated in Arm A.”
The phrase in bold was added to clarify the dose 
and schedule of BMS-813160 in Part 2 of the 
study.
1: Synopsis;
7: Treatment;
7.1: Treatments 
Administered
Addition of tablet dosage form of 
BMS-813160 to the study.
• Table 1-3 and Table 7-1: Study 
Treatments for CV202103.
• Table 1-4 and Table 7.1-1: Selection 
and Timing of Dose.
Study formulary updated with the addition of 
75-mg and 300-mg BMS-813160 tablets.
Revised Protocol No.: 06
Date: 05-Dec-2019
208
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 05
Section Number
& Title
Description of Change
Brief Rationale
3.1.7: Rationale for 
Testing BMS-813160 
in Combination with 
Nivolumab, 
Gemcitabine, and 
Nab-Paclitaxel
The following statement was added, 
“Based on the data available, the safety 
profile of BMS-813160 is manageable 
with either the 300 mg BID or 600 mg 
QD dose in combination with 
gemcitabine and nab-paclitaxel or 
nivolumab.” 
Statement added based on safety data available 
from Part 1 of the study.
3.1.8: Rationale for 
Exploring 
Monotherapy in 
Arm D
Section was reorganized and modified. Clarification.
3.2.1.3: Clinical 
Pharmacokinetics of 
BMS-813160
Preliminary PK evaluation in 
participants with advanced solid 
tumors receiving 300 mg BID or 
600 mg QD monotherapy dose 
(Study CV202103) was added.
Section updated based on preliminary PK data
available from Part 1 of the study.
5.4.6: Rationale for 
Using BMS-813160 
Tablet
Section added describing the rationale 
for the addition of tablet dosage form 
of BMS-813160 to the study.
Study formulary updated with the addition of 
75-mg and 300-mg BMS-813160 tablets.
5.5.1: Rationale for 
Dose Selection of 
BMS-813160
The following paragraph was added: 
“The selection of the Part 2 dose for 
BMS-813160 in CV202103 is 
primarily based on available data from 
Part 1 of CV202103. At 300 mg BID, 
preliminary PK data suggested similar 
average plasma levels of BMS-813160 
in cancer patients relative to that in 
healthy subjects. Based on the higher 
Cmax at steady state with the 600 mg 
QD dose and the lack of apparent 
difference in PD or safety between the 
300 mg BID and 600 mg QD dose, 
300 mg BID has been chosen as the 
primary dose to be evaluated in Part 2 
of the study.”
Rationale for the selection of BMS-813160 
300 mg BID dosing regimen for primary 
investigation in Part 2 of the study.
6.1: Inclusion 
Criteria, 2), b), i), 3
and 2), b), ii), 10
Criteria statements modified to be read 
as: “Participants must have received an 
oxaliplatin-containing regimen and an 
irinotecan- containing regimen (or a 
combined oxaliplatin- and irinotecan-
containing regimen) but no more than 
2 lines of systemic chemotherapy for 
metastatic disease.”
The phrase in bold was added to clarify the 
number of previous treatments permitted in 
Arms C and D of the study.
6.2: Exclusion 
Criteria, 2), r)
Participants who have received a 
live / attenuated vaccine within 30 days 
of first treatment.
Alignment with Nivolumab Investigator 
Brochure.
Revised Protocol No.: 06
Date: 05-Dec-2019
209
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 05
Section Number
& Title
Description of Change
Brief Rationale
7.7.1: Prohibited 
and/or Restricted 
Treatments
Any live / attenuated vaccine (eg, 
varicella, zoster, yellow fever, 
rotavirus, oral polio and measles, 
mumps, rubella [MMR]) during 
treatment and until 100 days post last 
dose.
Alignment with Nivolumab Investigator 
Brochure.
7.4.4: BMS-813160 
Dose Modifications
First bullet modified to be read as “..., 
Type 2 second or third-degree heart 
block will require dose interruption and 
restarting at one dose level lower when 
ECG changes resolve to baseline.”
Table 7.4.4-1 was modified to add 
BMS-813160 75 mg BID as a dose 
reduction for the BMS-813160 150 mg 
QD starting dose. 
The phrase in bold was added for clarification. 
A dose regimen of 75 mg QD using 75-mg 
BMS-813160 tablet can be used as an alternative 
the 150 mg QOD dose reduction.
7.4.7: Nivolumab 
Dose Modifications
Section updated to include text and link 
to Section 7.4.7.4, Treatment of 
Treatment-related Infusion Reactions.
Management of infusion reactions added to the 
protocol.
7.4.7.1: Dose Delays 
in Nivolumab 
(Cohort 3b of Arm B 
and All Cohorts of 
Arm C)
Criteria for treatment delays were 
updated.
Criteria were updated to align with nivolumab 
dose delay.
7.4.7.4: Treatment of 
Treatment-related 
Infusion Reactions
Section added describing treatment-
related infusion reactions and clinical 
guidance.
Section added to provide guidance on the 
treatment of nivolumab treatment reactions.
7.7.3: Permitted 
Therapy
Second bullet modified to add 
statement, “Corticosteroids are allowed 
for prophylaxis in the chemotherapy 
arms if clinically indicated as part of 
standard of care.”
Modified to allow prophylactic treatment with 
corticosteroids in the chemotherapy arms where 
appropriate.
8.4: Study 
Termination
Section added to describe the 
evaluation of benefit/risk leading to 
termination of all or part of the study.
Criteria added for study termination.
9.1: Efficacy 
Assessments
Section updated to provide guidance on 
unscheduled tumor assessments.
Clarification on submitting unscheduled imaging.
10.1: Sample Size 
Determination
Arm C: Cohort 5 (2/3L CRC [MSS]) in 
Table 10.1-1 was reorganized for 
clarity.
Clarification of 2- stage design for Cohorts 4 and 
5. 
Appendix 2: Study 
Governance 
Considerations
Modified Good Clinical Practice 
section to:
• Add bullet to clarify that the study 
will also be conducted in accordance 
with ethical principles derived from 
international guidelines, including 
Modified text to align with statement in the 
informed consent form and TransCelerate 
Common Protocol Template.
Revised Protocol No.: 06
Date: 05-Dec-2019
210
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 05
Section Number
& Title
Description of Change
Brief Rationale
the Declaration of Helsinki and 
Council for International 
Organizations of Medical Sciences 
International Ethical Guidelines 
Good Clinical Practice.
• Align with revised definition of 
serious breach to Regulation 
No 536/2014 of the European 
Parliament and of the Council.
Appendix 3: Adverse 
Events and Serious 
Adverse Events: 
Definitions and 
Procedures for 
Recording, 
Evaluating, Follow 
Up and Reporting
Events Meeting the AE Definition:
• “...medical and scientific judgement 
of the investigator. Note that 
abnormal lab tests or other safety 
assessments should only be 
reported as AEs if the final 
diagnosis is not available. Once the 
final diagnosis is known, the 
reported term should be updated 
to be the diagnosis.”
• “Overdose, as a verbatim term (as 
reported by the investigator), 
should not be reported as an 
AE/SAE unless it is an intentional 
overdose taken with possible 
suicidal/self-harming intent. Such 
overdoses should be reported 
regardless of sequelae and should 
specify "intentional overdose" as 
the verbatim term."
• 6th bulleted statement and last 
paragraph were deleted.
Events NOT Meeting the AE 
Definition:
• Previous text was deleted with the 
exception of the 3rd and 4th bulleted 
statements. 
DEFINITION OF SAE:
• “If an event is not an AE per 
definition above, then it cannot be an 
SAE even if serious conditions are 
met.” 
Text was modified and phrase in bold was added 
to clarify the need to report abnormal lab tests or 
other safety assessments when the final diagnosis 
is not available.
Text was modified and phrase in bold was added 
to clarify the need for the investigator to report 
the specific term of “intentional overdose” as an 
AE term. All other types of overdose should NOT 
be reported as an AE but should be recorded 
elsewhere on the CRF. There are no changes to 
the reporting of AEs associated with any type of 
overdose.
Text deleted to clarify that disease related events 
and events associated with lack of efficacy will 
need to continue to be reported as AEs if the 
event meets the criteria of an AE.
Text deleted to clarify that disease related events 
and events associated with lack of efficacy will 
need to continue to be reported as AEs if the 
event meets the criteria of an AE.
Text was deleted to clarify that disease related 
events and events associated with lack of efficacy 
will need to continue to be reported as AEs if the 
event meets the criteria of an AE. 
Revised Protocol No.: 06
Date: 05-Dec-2019
211
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 05
Section Number
& Title
Description of Change
Brief Rationale
Appendix 6: 
Management 
Algorithms, Hepatic 
Adverse Event 
Management 
Algorithm
Footnote stating I-O therapy may be 
delayed rather than discontinued if 
AST/ALT ≤8 x ULN or T.bili 
≤5 x ULN was removed.
Language was modified to align protocol with 
current Nivolumab Investigator Brochure and 
nivolumab program safety parameters.
All
Minor formatting and typographical
corrections.
Revised Protocol No.: 06
Date: 05-Dec-2019
212
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Overall Rationale for the Revised Protocol 04, 12-Jul-2018
The revised protocol adds a new table to Section 2, Schedule of Activities, clarifying the 
procedures needed for participants in Part 2 of the study to cross over from Cohorts 1c and 3c to 
Cohorts 5 and 4, respectively. Additional revisions include reordering the inclusion criteria from 
Revised Protocol 03, clarifying the biomarker sample collections for cross-over participants, and 
some administrative changes.
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 04
Section Number
& Title
Description of Change
Brief Rationale
2: Schedule of 
Activities
Mandatory pre-treatment biopsy 
assessments in Table 2-1 and Table 2-2 
were clarified to describe sufficient 
tumor tissue as 3 to 4 blocks or 
minimum of 30 slides.
Section was updated to include 
Table 2-2, Baseline for Cross-Over 
Procedural Outline - Cohort 1c to 
Cohort 5 - Cohort 3c to Cohort 4 -
Part 2. 
Table 2-7, Follow-up Procedural 
Outline, was modified to include 
cross-over, follow-up safety 
assessments.
Clarification.
Table 2-2 and Table 2-7 were added and 
modified, respectively, to clarify the procedures 
needed for participants in Part 2 of the study to 
cross over from Cohorts 1c and 3c to Cohorts 5 
and 4, respectively.
6.1: Inclusion 
Criteria
• Criterion 2), iii) was moved back to 
its original number as per Protocol 
Revision 02, criterion 2), b).
• The Protocol Revision 02 Part 2 
criteria 2), b), ii), 1 through 6 are not 
applicable as per Protocol 
Revision 03. 
• The Protocol Revision 03 Part 2 
criteria 2), a), ii), 1, 2, 3, and 4 are 
renumbered as 2), b), ii), 7, 8, 9, and 
10, respectively.
The study inclusion criteria were reordered to 
facilitate the transfer of this information in the 
electronic data capture system (RAVE). An edit 
check in RAVE will ensure that the site will 
select the accurate revised new criteria.
6.2: Exclusion 
Criteria
Criterion 2), d), iv) is not applicable as 
per Protocol Revision 04.
Criterion 2), o) was clarified to allow 
Whipple or other upper GI surgery if 
there is no clinical evidence of 
malabsorption. 
Criterion 2), p) is not applicable as per 
Protocol Revision 04.
Criterion 2), q) is not applicable as per 
Protocol Revision 04.
Clarification.
7.2: Method of 
Treatment 
Assignment
Section was updated to clarify that 
cross-over participants will retain their 
Clarification.
Revised Protocol No.: 06
Date: 05-Dec-2019
213
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 04
Section Number
& Title
Description of Change
Brief Rationale
original personal identification 
numbers throughout the study.
7.4.4: BMS-813160 
Dose Modifications
Table 7.4.4-1, Recommended Dose 
Modifications for BMS-813160, was 
updated to include a dose reduction for 
participants receiving 300 mg QD.
Clarification.
9.8: Biomarkers
Table 9.8-2 was modified to align with 
the cross-over sample collections in 
Part 2 of the study.
The peripheral blood mononuclear 
cells (PBMC) sample collections in 
Table 9.8-2, Biomarker Sampling 
Schedule - Part 2, were replaced with 
blood sample collections. 
Table was modified to clarify the biomarker 
sample collections for cross-over participants.
Evolving science indicates that the best collection 
for the peripheral gene expression profiling 
analysis is whole blood PAXgene® instead of 
whole blood with isolated PBMC. 
10.3.1: Efficacy 
Analyses
Section updated to clarify that 
participants reassigned into Arm C 
cohorts following treatment in another 
cohort, will be combined with 
participants originally assigned in these 
cohorts for efficacy analysis.
Clarification.
All
Minor formatting and typographical
corrections.
Clarification.
Revised Protocol No.: 06
Date: 05-Dec-2019
214
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Overall Rationale for the Revised Protocol 03, 07-May-2018
The revised protocol adds and modifies disease-specific cohorts, study treatments, PK, and 
biomarker assessments. Additional revisions include clarifying and alignment modifications to the 
clinical protocol template and some administrative changes. 
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
1: Synopsis;
3.1.3: Rationale for 
the Chemotherapy 
Regimens in Arms A 
and B;
3.1.4: Rationale for 
Selecting 2L CRC in 
Part 2 Arm A;
3.1.5: Rationale for 
Combining 
BMS-813160 with 
Nivolumab in 
Patients with 
Advanced Pancreatic 
and Colorectal 
Cancers in Arm C;
3.1.6: Rationale for 
Testing Lower Dose 
of BMS-813160;
3.1.7: Rationale for 
Testing BMS-813160 
in Combination with 
Nivolumab, 
Gemcitabine, and 
Nab-Paclitaxel;
3.1.8: Rationale for 
Exploring 
Monotherapy in Arm 
D;
5.1: Overall Design;
5.1.3: Treatment 
Period (Part 2);
5.1.4: Treatment 
Period (Parts 1 and 
2);
7.1: Treatments 
Administered
Figure 1-2 and Figure 5.1-2, Study 
Design Schematic (Part 2), modified as 
follows:
• Cohorts 1a, 1b, and 1c (2L CRC) 
replaced Cohort 1 (1L CRC) and 
Cohort 2 (3L CRC). Two new 
treatments were added: Cohort 1b, 
low dose BMS-813160 + 
FOLFIRI, and Cohort 1c, FOLFIRI 
treatment comparator.
• Cohort 3 (1L pancreatic) was 
divided into Cohorts 3a, 3b, and 3c 
(1L pancreatic). Two new 
treatments were added: Cohort 3b, 
BMS-813160 + nivolumab + 
Gem/nab-paclitaxel, and Cohort 
3c, Gem/nab-paclitaxel treatment 
comparator.
• FOLFIRI retreatment (cohort 2) 
and Colorectal MSI-H (cohort 6 
and 9) were removed from Part 2, 
Arm C and Arm D.
Cetuximab and panitumumab treatment 
options removed as potential additions 
to FOLFIRI therapy (Part 2) 
throughout the protocol.
Cohort 3b (1L pancreatic), 
BMS-813160 + nivolumab + 
Gem/nab-paclitaxel treatment, added 
with a safety lead-in with staggered 
dosing (sentinel participant) approach.
Study treatment rationale sections 
added or updated to describe 
modifications to Part 2 of the study, 
combination therapy expansion.
• Randomization was added to Part 2 to better 
evaluate safety and efficacy of the 
BMS-813160 + chemotherapy combination. 
A second dose was added to Arm A to test 
PK, PD, and efficacy of lower dose of 
BMS-813160 in combination with 
chemotherapy. 
• Randomization was added to Part 2 to better 
evaluate safety and efficacy of BMS-813160 
+ chemotherapy +/- nivolumab.
A combination of BMS-813160 + nivolumab 
+ Gem/nab-paclitaxel combination was added 
to Arm B to evaluate safety and preliminary 
efficacy of the combination. 
• FOLFIRI retreatment and MSI-H post PD-1 
cohorts were removed from the study.
Bevacizumab can be added to 2L FOLFIRI 
treatment if appropriate. 
A staggered dosing (sentinel participant) 
approach and safety lead in will reduce the 
number of patients enrolled to the combination if 
there are any unanticipated toxicities.
1: Synopsis;
Table 1-2 and Table 4-2, Objectives 
and Endpoints (Part 2), were updated 
Study objectives and endpoints were updated to 
align with revisions to the Part 2 study design. 
Revised Protocol No.: 06
Date: 05-Dec-2019
215
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
4: Objectives and 
Endpoints
to include BMS-813160 in 
combination with nivolumab + Gem + 
nab-paclitaxel (Arm B) and as 
monotherapy (Arm D).
1: Synopsis;
5.5.1: Rationale for 
the Dose Selection of 
BMS-813160;
7.1: Treatment 
Administered;
7.4.4: BMS-813160 
Dose Modifications
Treatment Period (Part 1), Table 1-4, 
Table 7.1-1, Table 7.4.4-1, and section 
text modified to remove the 
exploratory BMS-813160 600 mg BID 
dosing regimen.
The exploratory BMS-813160 600 mg BID 
dosing regimen was not initiated in Part 1 of the 
study, and this regimen will not be explored in 
Part 2.
1: Synopsis;
5.1.4: Treatment 
Period (Parts 1 and 2)
Treatment Period (Part 2) modified to 
permit eligible participants in Cohorts 
1c and 3c to cross over to Cohorts 5 
and 4, respectively, at the time of 
disease progression. Participants will 
have to meet all eligibility criteria to 
re-enter the study.
Eligible participants on the control arms of 
Arm A and B will be allowed to cross over at the 
time of PD as they may be eligible for Arm C.
1: Synopsis;
2: Schedule of 
Activities;
5.1: Overall Design;
8.1.1: Post Study 
Treatment Study 
Follow-up
Safety Follow-up Period (Parts 1 and 
2), Figure 1-2, Table 2-1, Table 2-3, 
Table 2-6, and Figure 5.1-2 updated to 
include participants in Cohort 3b (Arm 
B, Part 2) to be followed for at least 
100 days after last dose of study 
treatment.
Follow-up period extended to monitor for AEs,
accounting for the long half-life of nivolumab.
1: Synopsis;
5.2: Number of 
Participants
Overall number of participants in Part 
2 revised. Participants per cohort in 
Part 2 updated.
Sections were updated to align with revisions in
Part 2 of the study design and Section 10.1, 
Sample Size Determination.
2: Schedule of 
Activities
References to PK sampling Table 
9.5.2-2 were removed from Table 2-1 
to Table 2-5. 
References to PK sampling Table 
9.5.4-2 were added to Table 2-2 and 
Table 2-3.
References to PK sampling Table 
9.5.3-1 were added to Table 2-4 and 
Table 2-5.
Reference to Table 9.8-2, Biomarker 
Sampling Schedule - Part 2, added to 
Table 2-1 to Table 2-5. 
Table 2-3, On-treatment Procedural 
Outline (Arm B), modified with 
additional study treatment, BMS-
Section 2 timing and events tables were updated 
to align with revisions in Part 2 of the study 
design. 
Revised Protocol No.: 06
Date: 05-Dec-2019
216
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
813160 + Gem/nab-paclitaxel + 
nivolumab, for Cohort 3b in Part 2.
EOT assessments were updated in 
Table 2-4 and Table 2-5 for Vital 
Signs, ECOG, 12-Lead ECG.
3.2.1.4: Clinical 
Safety of 
BMS-813160
Section updated with an on-going 
safety evaluation of BMS-813160 
2-week monotherapy lead-in and 
combination with chemotherapy or 
nivolumab in Part 1.
On-going clinical safety update of BMS-813160 
in Part 1 provided.
3.2.2.2: Clinical 
Pharmacokinetics of 
Nivolumab
Section updated with recent US FDA 
and EU CHMP approvals for 
nivolumab 480 mg Q4W treatment 
regimen.
Section updated with recent regulatory approvals.
3.3: Benefit/Risk 
Assessment
Section updated to include the 
combination of Gem/nab-paclitaxel, 
nivolumab, and BMS-813160 
(Cohort 3b).
A Gem/nab-paclitaxel, nivolumab, and 
BMS-813160 combination was added to Arm B 
to evaluate safety and preliminary efficacy of the 
combination.
5.1.2: Treatment 
Period (Part 1)
Section updated to add participants for 
the PK and PD assessments of lower 
doses of BMS-813160 in combination 
with nivolumab.
The Sponsor proposes to add lower doses that 
provide a trough concentration of 0.3 to 0.5-fold 
IC90 for inhibiting CCR2/5 function.
5.4.4: Rationale for 
Control Arms
The control arms for Arm A 
(FOLFIRI) and Arm B 
(Gem/nab-paclitaxel) were added.
Control arms were added to better evaluate safety 
and efficacy of BMS-813160 combined with 
either FOLFIRI or Gem/nab-paclitaxel ±
nivolumab, respectively.
5.5.2: Rationale for 
Lower Dose of BMS-
813160
Lower doses of 150 mg QD and 
300 mg QD to be evaluated in the 
study.
The Sponsor proposes to add lower doses that 
provide a trough concentration of 0.3 to 0.5-fold 
IC90 for inhibiting CCR2/5 function.
6.1: Inclusion 
Criteria, 2), a), ii), 1. 
to 5.
Inclusion criteria modified for 
disease-specific cohorts.
Criterion moved to 2), a), iii) from 2), 
b).
Clarification.
6.2: Exclusion 
Criteria, 1), b)
Eligibility criteria added for 
participants with adequately treated 
CNS metastasis.
Clarification.
6.2: Exclusion 
Criteria, 5), e), i)
New exception, intraventricular 
conduction delay which is not 
considered clinically significant, was 
added to QRS ≥120 msec exclusion 
criterion. 
Clarification.
6.2: Exclusion 
Criteria, 7), a)
Eligibility of prisoners or participants 
who are involuntarily incarcerated was 
modified to include prohibitions by 
local regulations/guidelines/laws.
Clarifications.
Revised Protocol No.: 06
Date: 05-Dec-2019
217
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
6.3.1: Meals and 
Dietary Restrictions
Section was modified to align with 
intensive PK sampling in Part 2.
Section updated to require fasting on C2D1 for 
PK characterization. 
6.4: Screen Failures
New phrasing added to CONSORT 
statement.
New phrase added, ‘...as applicable,...’ to 
CONSORT statement to enable use of the section 
without change or editing, as it will be applicable 
to all interventional protocols.
7.4.4: BMS-813160 
Dose Modifications
Qualifying phrase, ‘unless the delay 
was from chemotherapy alone or 
unrelated to study treatment’, added to 
5th bulleted statement.
Two bulleted statements were added 
regarding participants who miss a dose 
at the specified time or vomit a dose.
Dose Reduction 2 was removed from 
Table 7.4.4-1.
Lower dose BMS-813160 treatment 
(Cohort 1b) added to the dose 
modification table to align with 
revisions in Part 2 of the study design.
Clarification regarding dose modification.
Starting doses of BMS-813160 and only one dose 
reduction added to all doses. 
7.4.5: FOLFIRI Dose 
Modifications
Dose Reduction 2 for Infusion 5-FU in 
Table 7.4.5-1 reduced to 1600 mg/m2
from 2000 mg/m2.
Clarification for dose modification of FOLFIRI.
7.7.3: Permitted 
Therapy
Section was added to describe qualified 
therapy with corticosteroids, 
immunosuppressive agents, and 
influenza vaccines.
Clarification on permitted therapy while on study.
7.7.4: Palliative 
Local Therapy
Section was added to describe 
palliative and supportive care for 
disease-related symptoms and study 
documentation.
Clarification allowing palliative and local 
therapy.
8.1: Discontinuation
Text added to align with TransCelerate 
clinical protocol template (CPT) and 
clarify expectations for reporting 
pregnancy.
Text added to align with TransCelerate CPT and 
clarify expectations for reporting pregnancy.
9.1: Efficacy 
Assessments
Text added to align with updated 
Appendix 5, Response Evaluation 
Criteria in Solid Tumors Guidelines 
(Version 1.1) with BMS Modifications.
Appendix was updated to harmonize language for 
RECIST 1.1 criteria across immuno-oncology 
program.
9.2.1: Time Period 
and Frequency for
Collecting AE and 
SAE Information
Text in section is reorganized.
Changes made to clarify timing to start collection 
of SAE from signing of consent and AE 
collection from the start of study treatment.
9.2.2: Method of 
Detecting AEs and 
SAEs
Section and text added to align with 
TransCelerate CPT.
Section and text added to align with 
TransCelerate CPT.
Revised Protocol No.: 06
Date: 05-Dec-2019
218
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
9.2.5: Pregnancy
New text added to clarify the 
circumstances for continuation of study 
treatment after confirmation of end of 
pregnancy.
Alignment with Section 8.1, Discontinuation 
from Study Treatment in Study Protocol.
9.3: Overdose
The requirement to report all 
occurrences of overdose as SAE is 
deleted.
Overdoses that meet the regulatory definition of 
SAE will be reported as an SAE.
9.5: 
Pharmacokinetics
Subsection headings, table titles, and 
section text modified to include the 
revised cohorts in Part 2.
Section updated to align with revisions in Part 2 
of the study design.
9.8: Biomarkers
Table 9.8-2, Biomarker Sampling 
Schedule - Part 2, added with an 
updated biomarker panel of 
assessments. Section text modified to 
include biomarker panel for Part 2.
Section updated to align with revisions in Part 2 
of the study design.
10.1: Sample Size 
Determination
The statistical analyses and participant 
population in Part 2 of the study were 
updated.
Section modified to align with revisions in Part 2 
of the study design.
10.3: Statistical 
Analyses
A description of the participant 
population will be included in the 
statistical output reported, including 
subgroup of age, gender, and race.
Sentence added to meet the compliance 
requirement of the Global Data Privacy 
Regulation and the MR-001 (for France) for the 
collection of ‘Race.’
10.3.1: Efficacy 
Analyses
Statistical analysis method updated to 
include an estimate of difference in 
ORR between each treatment cohort 
and the control cohort of Arm A and 
Arm B and corresponding two-sided 
exact 95% CI by treatment for each 
tumor type.
Text added to align with revisions in Part 2 of the 
study design.
10.3.2: Safety 
Analyses
Section was updated to include Cohort 
3b in Part 2.
Text added to align with revisions in Part 2 of the 
study design.
Appendix 2: Study 
Governance 
Considerations; Good 
Clinical Practice; 3rd 
paragraph
Revised definition of serious breach.
Revised definition to serious breach according to 
REGULATION (EU) No 536/2014 OF THE 
EUROPEAN PARLIAMENT AND OF THE 
COUNCIL of 16 April 2014 on clinical trials on 
medicinal products for human use.
Appendix 3: Adverse 
Events and Serious 
Adverse Events: 
Definitions and 
Procedures for 
Recording, 
Evaluating, Follow 
Up and Reporting
New sections, Events Meeting the AE 
Definition and Events NOT Meeting the 
AE Definition, and text added.
For SAE reporting, deleted cancer, 
overdose, suspected transmission of an 
infectious agent.
Pregnancy and potential drug-induced 
liver injury (DILI) statements clarified.
Assessment of Causality text revised.
New Sections and text added to align with 
TransCelerate CPT.
Align with regulatory definition (EMA GVP 
Module VI (EMA/873138/2011) and ICH E2A).
Clarify the timeline/process for reporting 
pregnancy and DILI.
Assessment of Causality text revised to align with 
TransCelerate CPT.
Revised Protocol No.: 06
Date: 05-Dec-2019
219
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Summary of key changes for Revised Protocol 03
Section Number
& Title
Description of Change
Brief Rationale
Appendix 10: 
Response Evaluation 
Criteria in Solid 
Tumors Guidelines 
(Version 1.1) with 
BMS Modifications
Fluid collections (ie, pleural effusions, 
pericardial effusions and ascites) will 
not be followed as non-target lesions 
and will not contribute to response or 
progression.
Removed timeframe for minimum time 
of study and definition of Day 1 to 
declare SD since this can vary per 
study. This is now outlined in the 
actual body of the protocol and 
specified per study requirements.
Appendix was updated to harmonize language for 
RECIST 1.1 criteria across immuno-oncology 
program.
1: Synopsis
Data Monitoring Committee: No
New field added to align with TransCelerate CPT, 
and a multi-layered process to ensure safety 
monitoring is described.
All
Minor formatting and typographical
corrections.
Clarification.
Revised Protocol No.: 06
Date: 05-Dec-2019
220
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Overall Rationale for the Revised Protocol 02, 11-Sep-2017
The revised protocol provides additional survival follow-up, tumor markers, PK sampling of 
irinotecan and nab-paclitaxel in a subset of participants and some administrative changes. 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02
Section Number 
& Title
Description of Change
Brief Rationale
1: Synopsis; 
4: Objectives and 
Endpoints
Objectives and Endpoints (Part 1 and 
Part 2) were updated to include 
exploratory objectives and endpoints 
assessing overall survival in treated 
participants.
Objectives and Endpoints (Part 2) were 
updated to include an exploratory 
objective and endpoint assessing the 
effect of irinotecan and nab-paclitaxel in 
a subset of participants by comparing 
with historical data.
Overall survival is being added as an exploratory 
endpoint as a direct measure of clinical benefit.
 
pharmacokinetics (PK) samples will be collected 
to assess the potential for a drug-drug 
interaction.
1: Synopsis; 
2: Schedule of 
Activities
5.1: Overall 
Design
5.1.5.2: Survival 
Follow-up
Section was added to describe a Survival 
Follow-up period. Survival Follow-up to 
begin after completion of Safety Follow-
up every 12 weeks (Q12W) [± 2 weeks] 
until 2 years after last dose of study 
treatment.
Table 2-6 was modified to include 
Survival Follow-up Q12W after Safety 
Follow-up Phase.
Follow-up Period modified in Study 
Schemes (Figure 5.1-1 and Figure 5.1-2) 
to include separate safety follow-up and 
survival follow-up phases.
A Survival Follow-up period was added to the 
study design and Schedule of Activities to assess 
the clinical benefit of study treatments.
Section 9.5.4: 
Pharmacokinetic 
Assessment of 
Irinotecan and 
Nab-Paclitaxel
Section 10.3.4: 
Irinotecan and 
Nab-Paclitaxel in 
Combination 
Phase (Part 2)
Sections added to describe the PK 
variables and sampling schedule for 
irinotecan (Arm A, Part 2, Cohort 1 only) 
and nab-paclitaxel (Arm B, Part 2) 
combinations therapies. 
 PK 
samples will be collected to assess the potential 
for a drug-drug interaction.
Section 9.8: 
Biomarkers
Section and Table 9.8-1 modified to 
include circulating tumor DNA (ctDNA) 
analysis and plasma sample schedule for 
ctDNA, respectively. 
Collection of plasma ctDNA for analysis will 
enable assessments of tumor mutations, tumor 
mutation burden, and other biomarkers.
Section 10.3.8: 
Other Analyses
Section modified to describe analysis of 
added exploratory objective related to 
overall survival.
Overall survival is being added as an exploratory 
endpoint as a direct measure of clinical benefit..
Revised Protocol No.: 06
Date: 05-Dec-2019
221
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02
Section Number 
& Title
Description of Change
Brief Rationale
Section 9.4.4: 
Clinical Safety 
Laboratory 
Assessments
List of clinical laboratory assessments 
modified to include serum testing for 
amylase.
List of clinical laboratory assessments updated 
to align with amylase testing described in 
Nonhepatic Nonhematologic DLT [Section 
7.4.1, 3), a), v), (3)] and Guidelines for 
Permanent Discontinuation in Nivolumab 
(Arm C) [Section 7.4.7.3, 7), d)].
Section 2: 
Schedule of 
Activities
The footnotes for ± 3 day window for 
chemotherapy and ECG-specified 
schedules were moved in Tables 2-2 to 
2-5 to the table headings and table notes, 
respectively. 
Clarification.
Appendix 2: 
Study 
Governance 
Considerations
Study governance (Appendix 2) updated 
01-Aug-2017.
Clarification.
Appendix 4: 
Women of 
Childbearing 
Potential 
Definitions and 
Methods of 
Contraception
WOCBP guidance (Appendix 4) updated 
20-Jul-2017.
Clarification.
All
Minor formatting and typographical 
corrections
Clarification.
Revised Protocol No.: 06
Date: 05-Dec-2019
222
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
Overall Rationale for the Revised Protocol 01, 28-Jun-2017
The revised protocol 
 includes administrative 
changes outlined in the Administrative Letter 01. 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01
Section Number 
& Title
Description of Change
Brief Rationale
1: Synopsis; 
5.1.2: Treatment 
Period (Part 1); 
5.2: Number of 
Participants;
10.1: Sample 
Size 
Determination
Protocol text was modified in order to 
clearly specify the sample size of every 
cohort, and statement "Sample sizes may 
need to be increased in order to explore 
differential responses between biomarker 
expressed and non-expressed groups" 
removed.
The number of subjects will be 
continuously monitored such that the 
number of evaluable participants in 
Part 2 will not exceed 40 per cohort for 
Cohorts 1 to 6 and 12 per cohort for 
Cohorts 7 to 9.
Number of patients in each cohort specified in 
Part 1 and 2.
The sample sizes for cohorts in Part 2 are based 
on the number of evaluable participants needed 
to support a decision whether or not a treatment 
is effective using target and historic response 
rates, while controlling Type 1 error.
1: Synopsis;
5.1.3: Treatment 
Period (Part 2)
Protocol text was modified to clearly 
state that the BMS-813160 dose in Part 2 
will not exceed the dose and schedule 
determined to be safe in Part 1.
6.1: Inclusion 
Criteria, 2), b), 
ii), 2.
Inclusion criteria was modified to require 
a prior oxaliplatin-containing regimen for 
all Arm A Cohort 2 ("3L Colorectal") 
metastatic CRC participants.
Inclusion criteria to ensure that patients received 
appropriate prior therapy.
6.1: Inclusion 
Criteria, 2), b), i), 
3.;
6.1: Inclusion 
Criteria, 2), b), 
ii), 5.
Inclusion criteria for participants with 
metastatic CRC on Arm C was updated 
to require prior therapy with an 
oxaliplatin-containing regimen and an 
irinotecan-containing regimen in the 
metastatic setting or a regimen 
combining oxaliplatin and irinotecan in 
the metastatic setting. 
Inclusion criteria was modified to ensure that 
participants received appropriate prior therapy. 
6.1: Inclusion 
Criteria, 2), b), 
ii), 6.
Inclusion criteria for participants with 
metastatic MSI-H CRC on Arm C was 
updated to also require prior therapy with 
an oxaliplatin-containing regimen and an 
irinotecan-containing regimen in the 
metastatic setting or a regimen 
combining oxaliplatin and irinotecan in 
the metastatic setting.
Inclusion criteria was modified to ensure that 
participants received appropriate prior therapy.
7.4.1: Dose 
Limiting 
Toxicity, 3), a), 
v), (1)
The DLT exception of Grade 4 
electrolyte or laboratory abnormalities 
was removed.
Grade 4 laboratory abnormalities will be 
considered DLT. 
Revised Protocol No.: 06
Date: 05-Dec-2019
223
7.0
Approved
930114148
7.0
v
Approved
1.0
v

Clinical Protocol
CV202103
BMS-813160
CCR2/5 Dual Antagonist
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01
Section Number 
& Title
Description of Change
Brief Rationale
1: Synopsis;
3.1.3: Rationale 
for the 
Chemotherapy 
Regimens in 
Arms A and B;
7.1: Treatments 
Administered
Administration of bevacizumab, 
cetuximab, or panitumumab is allowed 
but not required as protocol-specified 
therapy. The biologic will be 
administered in accordance with local 
Health Authority approved labeling for 
these agents.
Administration of biologics was updated to 
acknowledge different local standard of care 
practices. 
7.4.1.1: Stopping 
Rules During 
Part 2
Section added to describe the safety 
stopping rules during Part 2 of the study.
Safety stopping rules added for Part 2 of the 
study.
9.4.4: Clinical 
Safety 
Laboratory 
Assessments
List of clinical laboratory assessments 
modified to include serum testing for 
hepatitis C antibody.
List of clinical laboratory assessments updated 
to align with hepatitis C testing described in 
exclusion criteria (Section 6.2, e, ii).
9.8: Biomarkers
Table 9.8-1 modified to remove PBMC 
sample collections and align tumor 
sample collection with the on-treatment 
procedural outlines for Arms A, B, C, 
and D.
PBMC sample collections are not needed.
2: Schedule of 
Activities
Table 2-2 modified to align ECG 
footnote (b) with the on-treatment 
procedural outlines for Arms B, C, and 
D.
Correction of error in Table for Arm A.
All
Minor formatting and typographical 
corrections
Clarification.
Revised Protocol No.: 06
Date: 05-Dec-2019
224
7.0
Approved
930114148
7.0
v
Approved
1.0
v