Clinical trial NCT03936959
Conditions: Advanced Cancer
Keywords: PD-1 PD-L1
Sponsor: Eli Lilly and Company
Start date: 2019-05-24; Completion date: 2021-04-29
Enrollment: 10 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3434172, a PD-1/PD-L1 bispecific antibody, in participants with advanced solid tumors.

Detailed description:

Arms: arm 1: 3 mg LY3434172 administered intravenously (IV) on Day 1 Cycle 1 of 28-day cycle. 10 mg LY3434172 administered IV on Day 15 Cycle 1 of 28-day cycle.

Participants continued to receive study treatment until they met a criterion for discontinuation. arm 2: 30 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation. arm 3: 100 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.
Interventions: intervention 1: LY3434172
Intervention descriptions: intervention 1: Administered IV

Protocol documents:
Prot_000.pdf: 
J1E-MC-JZEA Protocol (b) 
 
A Phase 1 Study of LY3434172, a Bispecific Antibody Monotherapy in Advance Solid Tumors 
 
NCT03936959 
 
Approval Date: 02-Dec-2019 


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1
L Y 3 4 3 4 1 7 2
Pr ot o c ol J 1 E -M C -J Z E A ( b)
A P h a s e 1 St u d y  of L Y 3 4 3 4 1 7 2, a Bi s p e cifi c Anti b o d y  
M o n ot h er a p y i n Ad v a n c e d S oli d T u m or s
C o nfi d e nti al I nf or m ati o n
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of 
cli ni c al i n v e sti g at or s.  It i s t h e pr o p ert y of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d 
s h o ul d n ot b e c o pi e d b y or di stri b ut e d t o p er s o n s n ot i n v ol v e d i n t h e cli ni c al i n v e sti g ati o n of 
L Y 3 4 3 4 1 7 2 , u nl e s s s u c h p er s o n s ar e b o u n d b y a c o nfi d e nti alit y a gr e e m e nt wit h Eli Lill y 
a n d C o m p a n y or it s s u b si di ari e s.  
N ot e t o R e g ul at or y A ut h oriti e s:   T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p er s o n al d at a 
a n d/ or c o m m er ci all y c o nfi d e n ti al i nf or m ati o n e x e m pt fr o m p u bli c di s cl o s ur e.  Eli Lill y a n d 
C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o a n y p u bli c r el e a s e.  I n 
t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) 
E x e m pti o n 4 a n d m a y n ot b e r e pr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n 
a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s.
L Y 3 4 3 4 1 7 2
Eli Lill y a n d C o m p a n y
I n di a n a p oli s, I n di a n a U S A 4 6 2 8 5
Pr ot o c ol El e ctr o ni c all y Si g n e d a n d A p pr o v e d b y Lill y:  0 7 D e c e m b er 2 0 1 8
A m e n d m e nt ( a) El e ctr o ni c all y Si g n e d a n d A p pr o v e d b y Lill y :  2 6 F e br u ar y 2 0 1 9
A m e n d m e nt ( b) El e ctr o ni c all y Si g n e d a n d A p pr o v e d b y Lill y
o n a p pr o v al d at e pr o vi d e d b el o w
A p pr o v al D at e: 0 2- D e c- 2 0 1 9 G M T


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Table of Contents
Section
Page
Protocol J1E-MC-JZEA(b)  A Phase 1 Study of LY3434172, a Bispecific 
Antibody Monotherapy in Advanced Solid Tumors.............................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................8
2.
Schedule of Activities .......................................................................................................11
3.
Introduction ......................................................................................................................22
3.1.
Study Rationale............................................................................................................22
3.2.
Background..................................................................................................................22
3.3.
Benefit/Risk Assessment..............................................................................................25
4.
Objectives and Endpoints..................................................................................................26
5.
Study Design.....................................................................................................................27
5.1.
Overall Design .............................................................................................................27
5.1.1.
Dose Escalation....................................................................................................28
5.2.
Number of Patients.......................................................................................................29
5.3.
End of Study Definition ...............................................................................................29
5.4.
Scientific Rationale for Study Design...........................................................................29
5.5.
Justification for Dose ...................................................................................................29
6.
Study Population...............................................................................................................31
6.1.
Inclusion Criteria..........................................................................................................31
6.2.
Exclusion Criteria ........................................................................................................33
6.3.
Lifestyle Restrictions....................................................................................................36
6.4.
Screen Failures.............................................................................................................36
7.
Treatment..........................................................................................................................37
7.1.
Treatment Administered...............................................................................................37
7.1.1.
Packaging and Labeling .......................................................................................37
7.2.
Method of Treatment Assignment ................................................................................38
7.2.1.
Selection and Timing of Doses.............................................................................38
7.2.2.
Dose Escalation....................................................................................................38
7.2.2.1.
Dose Escalation Method.................................................................................38
7.2.2.2.
Dose-Limiting Toxicity Determination ...........................................................39
7.2.2.2.1.
Events That Are Not Considered to Be DLTs............................................41
7.2.2.2.2
DLT-Equivalent Toxicities .......................................................................41
7.2.2.3.
Recommended Phase 2 Dose Determination...................................................41
7.3.
Blinding .......................................................................................................................42
7.4.
Dose Modification........................................................................................................42


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
7.5.
Preparation/Handling/Storage/Accountability...............................................................49
7.6.
Treatment Compliance .................................................................................................49
7.6.1.
Evaluable Patients................................................................................................49
7.6.1.1
DLT-Evaluable Patients in Phase 1 Dose Escalation.......................................49
7.7.
Concomitant Therapy...................................................................................................49
7.8.
Treatment after the End of Study..................................................................................50
7.8.1.
Treatment after Study Completion........................................................................50
7.8.1.1.
Continued Access...........................................................................................50
8.
Discontinuation Criteria ....................................................................................................52
8.1.
Discontinuation from Study Treatment.........................................................................52
8.1.1.
Discontinuation of Inadvertently Enrolled Patients...............................................53
8.2.
Discontinuation from the Study....................................................................................53
8.3.
Lost to Follow-Up........................................................................................................53
9.
Study Assessments and Procedures ...................................................................................54
9.1.
Efficacy Assessments...................................................................................................54
9.1.1.
RECIST 1.1 with Confirmatory Scan for Disease 
Progression ..........................................................................................................55
9.1.1.1.
Rationale for RECIST 1.1 with Confirmatory Scan for 
Disease Progression........................................................................................55
9.1.1.2.
Application of RECIST 1.1 with Confirmatory Scan for 
Disease Progression........................................................................................56
9.1.1.3.
Criteria Required to Receive Treatment during 
Confirmatory Scan Period...............................................................................57
9.2.
Adverse Events ............................................................................................................57
9.2.1.
Serious Adverse Events........................................................................................58
9.2.2.
Suspected Unexpected Serious Adverse Reactions ...............................................59
9.2.3.
Complaint Handling.............................................................................................59
9.3.
Treatment of Overdose.................................................................................................59
9.4.
Safety...........................................................................................................................59
9.4.1.
Safety Measures...................................................................................................59
9.4.1.1.
Electrocardiograms.........................................................................................60
9.4.2.
Safety Monitoring ................................................................................................61
9.4.2.1.
Guidance for Monitoring Vasculitis................................................................62
9.4.2.2.
Special Hepatic Safety Data Collection...........................................................63
9.5.
Pharmacokinetics .........................................................................................................63
9.6.
Pharmacodynamics ......................................................................................................63
9.6.1.
Immunogenicity Assessments ..............................................................................63
9.7.
Genetics .......................................................................................................................64
9.7.1.
Whole Blood Sample for Pharmacogenetic Research ...........................................64


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
9.8.
Biomarkers...................................................................................................................65
9.8.1.
Tissue Samples for Biomarker Research...............................................................65
9.8.2.
Other Samples for Biomarker Research................................................................67
9.9.
Health Economics ........................................................................................................67
10.
Statistical Considerations ..................................................................................................68
10.1. Sample Size Determination ..........................................................................................68
10.2. Populations for Analyses..............................................................................................68
10.3. Statistical Analyses ......................................................................................................68
10.3.1.
Safety Analyses....................................................................................................68
10.3.2.
Efficacy Analyses ................................................................................................69
10.3.3.
Other Analyses.....................................................................................................70
10.3.3.1.
Patient Disposition..........................................................................................70
10.3.3.2.
Patient Characteristics ....................................................................................70
10.3.3.3.
Concomitant Therapy .....................................................................................70
10.3.3.4.
Treatment Compliance....................................................................................70
10.3.3.5.
Pharmacokinetic/Pharmacodynamic Analyses ................................................71
10.3.3.6.
Biomarker Analyses .......................................................................................71
10.3.3.7.
Immunogenicity Analyses ..............................................................................71
10.3.4.
Interim Analyses ..................................................................................................72
11.
References ........................................................................................................................73
12.
Appendices .......................................................................................................................76


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
List of Tables
Table
Page
Table JZEA.1
Baseline and On-Study Treatment Schedule of Activities (Cohort A1, 
A2, A3, A4, A5, and A6)...............................................................................12
Table JZEA.2
Baseline and On-Study Treatment Schedule of Activities (Cohort A7 
and A8)..........................................................................................................16
Table JZEA.3.
Poststudy Treatment Schedule of Activities (All Parts)..................................20
Table JZEA.4.
Continued Access Schedule of Activities .......................................................21
Table JZEA.5.
Summary of 1-month Repeat-Dose Monkey Toxicity Study with 
LY3434172 ...................................................................................................25
Table JZEA.6.
Objectives and Endpoints...............................................................................26
Table JZEA.7.
Treatment Regimen .......................................................................................37
Table JZEA.8.
Dose-Limiting Toxicity .................................................................................40
Table JZEA.9.
Management of Infusion-Related Reactions (IRR).........................................43
Table JZEA.10. Dose Modification Guidelines and AE Management for Toxicities At 
Least Possibly Related to Study Drug ............................................................44
Table JZEA.11. Summary of Response Assessment by RECIST, RECIST with 
Confirmatory Scan for PD, and irRC .............................................................56


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
List of Figures
Figure
Page
Figure JZEA.1.
Illustration of study design.............................................................................28
Figure JZEA.2.
Continued access diagram..............................................................................51


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................77
Appendix 2.
Clinical Laboratory Tests...............................................................................83
Appendix 3.
Study Governance, Regulatory and  Ethical Considerations ...........................85
Appendix 4.
Sampling Schedule ........................................................................................88
Appendix 5.
Restricted and Prohibited Concomitant Medications ....................................100
Appendix 6.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality..................102
Appendix 7.
Creatinine Clearance Formula......................................................................103
Appendix 8.
Dose-Finding Algorithm of the Modified Toxicity Probability Interval 
(mTPI-2) Method Showing Number of Patients Treated ..............................104
Appendix 9.
Definition of Woman of Childbearing Potential ...........................................106
Appendix 10.
Protocol Amendment J1E-MC-JZEA(b) Summary A Phase 1 Study of 
LY3434172, a Bispecific Antibody Administered as a Monotherapy in 
Advanced Solid Tumors ..............................................................................107


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
1. Synopsis
Protocol Title:
A Phase 1 study of LY3434172, a bispecific antibody administered as a monotherapy in 
advanced solid tumors.
Rationale:
T-cells play a central role in immune response to tumor.  However, tumors have adopted 
multiple mechanisms to evade host immune surveillance.  One of the key mechanisms is the up-
regulation of immune suppressive co-inhibitory molecules (immune checkpoint molecules) on 
the tumor cells.  The programmed cell death protein-1 receptor (PD-1) axis is one of the 
dominant co-inhibitory pathways in T-cell activation.  This axis involves three interactions.  
Both programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) ligands, 
expressed by antigen presenting cells (APC), can bind to PD-1 receptor on T-cells.  In addition, 
PD-L1 can also bind to B7-1, which is upregulated along with PD-1 upon initial T-cell activation 
by antigen stimulation.  These interactions lead to suppression of T-cell activation.  In a variety 
of tumors, PD-L1 is frequently over-expressed by tumor cells, contributing to the immune 
tolerant state known as T-cell exhaustion.  However, blocking the PD-1 axis has been shown to 
remove this suppression and reinvigorate T-cell activation.
While anti-PD-1 and anti-PD-L1 antibodies have demonstrated durable clinical responses in 
multiple tumor indications, only a subset of patients benefit from these treatments and there is 
room for further improvement. In vitro experiments have demonstrated that LY3434172 can 
bridge cells engineered to express PD-1 and those that express PD-L1. This enhances cell-based 
functional activity in vitro and antitumor efficacy in vivo compared to monoclonal antibody
(mAb) monotherapy or combination; hence, the bispecific antibody (bsAb) may have the 
potential to improve upon the biological activity of existing PD-1 and PD-L1 agents, either alone 
or in combination. Clinical relevance of bridging is unknown at this time. The goal of this study 
is to establish the safety and recommended Phase 2 dose (RP2D) of LY3434172 administered as 
monotherapy to patients with advanced solid tumors.  


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 9
L Y 3 4 3 4 1 7 2
O bjecti ves a n d E n d p oi nts
O bjecti ves
E n d p oi nts
Pri m ar y
T o assess t he safet y a n d t olera bilit y of L Y 3 4 3 4 1 7 2, t here b y 
i de ntif yi n g a R P 2 D of L Y 3 4 3 4 1 7 2, a d mi nistere d t o patie nts 
wit h a d va nce d s oli d t u m ors.

D L Ts

Safet y (i ncl u di n g b ut n ot li mite d t o): T E A Es, 
D L T -e q ui vale nt t o xicities, S A Es, deat hs, a n d 
cli nical la b orat or y a b n or malities per C T C A E 
( Versi o n 5. 0)
Sec o n d ar y
T o assess t he P K i n patie nts wit h s oli d t u m ors of 
L Y 3 4 3 4 1 7 2.

A U C, C mi n a n d a p pr o xi mate C ma x of 
L Y 3 4 3 4 1 7 2 
T o assess  preli mi nar y a ntit u m or acti vit y a of L Y 3 4 3 4 1 7 2 

O R R

D O R

T T R

D C R 
A b bre viati o ns: A U C = area u n der t he c ur ve; C ma x = ma xi m u m ser u m/ plas ma c o nce ntrati o n; C mi n = mi ni m u m 
ser u m/ plas ma c o nce ntrati o n; C T C A E = C o m m o n Ter mi n ol o g y Criteria i n A d verse E ve nts; D C R = disease 
c o ntr ol rate; D L T = d ose-li miti n g t o xicit y; D O R = d urati o n of res p o nse; OR R = o bjecti ve res p o nse rate;
P K = p har mac o ki netics; R E CI S T = Res p o nse E val uati o n Criteria i n S oli d T u m ors; R P 2 D = rec o m me n de d 
P hase 2 d ose; S A E = seri o us a d verse e ve nt; T E A E = treat me nt -e mer ge nt a d verse e ve nt; T T R = ti me-t o-res p o nse.
a
Res p o nse assess me nt usi n g R E CI S T 1. 1 a n d R E CI S T 1. 1 wit h c o nfir mat or y sca n f or disease pr o gressi o n.
O ver all Desi g n:
St u d y  J 1 E-M C -J Z E A (J Z E A) is a mul tice nter, n o nra n d o mize d, o pe n -label P hase 1 st u d y in 
pati e nts wit h a d va nce d s oli d t u m ors.
P hase 1 st u d y  will assess t he safety a n d t olera bilit y of L Y 3 4 3 4 1 7 2, a d mi nistere d as a 
m o n ot hera p y  in pat ient s wit h select a d va nce d s o li d t u m ors. St u d y  J Z E A will facilitate a 
t hor o u g h safet y e val uat i on a n d e x pl orat i on of p har mac o ki net ics (P K ) a n d p har mac o d y na mics 
effects
.  Once d ose -li miti n g 
t o xicit y ( D L T) perio d is c o m plete d f or res pecti ve C o h orts A 1 t o A 5 / 6 u p t o a p pr o xi matel y 1 2 t o 
1 5 a d ditio n al  pat ient s ma y be a d de d t o t w o d ose le vels selec te d fr o m t hese c o h orts.  F or 
e xa m ple, if 3 0 0 m g is a d ose le vel selecte d, a d dit i onal pat ient s ma y be e nr olle d i n parallel with 
C o h ort A 5 after C o h ort A 4 has cleare d D L T .  D o se escalati on will be dri ve n b y m o difie d 
t o xicit y pr o ba bilit y int er val 2 (m T PI 2 ) met h o d, e nr olli n g at least 3 patie nts per c o h o rt.  
I n a d diti on, a n e ver y  t hree wee ks (Q 3 W ) d osi n g sc he d ule ( C o h orts A 7 a n d A 8) will be e val uate d 
t o all o w f or fle xi bility f or fut ure c o m bi nat i ons wit h sta n dar d-of -care a ge nts t hat ma y use a Q 3 W 
d ose re gi me n . T he Q 3 W d osi n g sc he d ule c o ul d be i nit iate d as C o h orts A7 a n d A8 i n parallel 
wi t h t he Q 2 W e x pa nsi o n res pecti vel y.
I nteri m a nal yses will be c o n d ucte d at t he e n d of d ose escalati on fr om C o h ort A 1 t o A 5/ 6 at  
c o mplet i on of D L T peri o d acr oss t hese c o h orts. T he R P 2 D will be i de ntifie d after fi nal a nal yses 
u p o n c o m p leti o n of t his P hase 1 st u d y.
C CI


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1 0
L Y 3 4 3 4 1 7 2
N u m ber of P atie nts:
A p pr o xi matel y  1 5 t o 2 0 patie nts will be e nr olle d i n Q 2 W d ose escalati o n ( C o h orts A 1 t o A 6) , 
a p pr o xi matel y 1 2 t o 1 5 a d diti o nal pat ient s ma y be a d de d t o t w o c o h orts after d ose le vel has 
cleare d t he D L T p eri o d . T he sa m ple size of Q 3 W de pe n ds pri maril y o n P K pr ofiles a n d cli nical 
c o nsi derati o ns.
Tre at me nt Ar ms a n d D ur ati o n:
P ati e nts e nr olle d i n P hase 1 will recei ve L Y 3 4 3 4 1 7 2 m o n ot hera p y , as s h o w n i n t he f oll o wi n g 
ta ble. P ati e nts ma y c o nti n ue t o recei ve st u d y treat me nt u ntil t he y meet a criteri o n f or 
di sc o nti n uati on.
C CI


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
2. Schedule of Activities
Table JZEA.1 presents the Baseline and On-study Schedule of Activities for all patients (for each 
of the 28-day cycle).
Table JZEA.2 presents the Baseline and On-study Schedule of Activities for all patients (for each 
of the 21-day cycle).
Table JZEA.3 presents the Post Treatment Follow-up Schedule of Activities for all patients (for 
each of the 21-day and 28-day cycle).
Table JZEA.4 presents the Continued Access Schedule of Activities for patients receiving 
LY3434172.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Table JZEA.1
Baseline and On-Study Treatment Schedule of Activities (Cohort A1, A2, A3, A4, A5, and A6)
Baseline
(Day 
Relative to 
C1D1)
Cycle = 28 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D15
D1
D15
D1
D15
D1
D15
Procedure
Informed consent
X
ICF must be signed before any protocol-specific procedures 
are performed
Inclusion/exclusion 
criteria
X
Medical history
X
Including assessment of preexisting conditions and historical 
illnesses
Cancer treatment 
history
X
Record prior anticancer therapy
Concomitant 
medication
X
X
At baseline, record prior and concurrent medications
Record all premedication, supportive care, and 
concomitant medication continuously at every visit and 
throughout the study
Physical 
examination
X
X
X
X
X
X
X
X
X

D1 visit should be completed by a physician.

Should include palpable tumor measurement.
Vital signs 
X
X
X
X
X
X
X
X
X
Measure vital signs (height (at baseline), weight, 
temperature, blood pressure, pulse rate, oxygen 
saturation, and respiration rate) as follows (±5 minutes):
In Cycles 1 through 3:
within 15 minutes prior to each LY3434172 infusion
every 15 minutes during each LY3434172 infusion
at the end of each LY3434172 infusion
A 4-hour observation period (See Section 5.1.1 and 7.4)
following the end of LY3434172 administration will occur in 
Cycles 1 to 3.
every 30 (±5) minutes for the first hour and 60 (±5) 
minutes thereafter during the 4-hour observation period


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 13
LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 28 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D15
D1
D15
D1
D15
D1
D15
In Cycle 4 and beyond, if the patient has not 
experienced an infusion-related reaction or other 
infusion-related AE:
up to 15 minutes prior to each LY3434172 infusion
at least once during each LY3434172 infusion
at the end of each LY3434172 infusion
AE collection
X
X
Collect continuously at every visit and throughout the 
study
CTCAE Version 5.0
ECOG PS
X
X
X
X
X
X
X
X
X
During study treatment, perform ≤3 days prior to D1 and D15
of each cycle.
ECHO
X
See 
Instructions
Perform locally, at baseline, Cycle 4 Day 1, and as clinically 
indicated
ECG
See Appendix 4 for ECG collection instructions
Blood tumor 
markers
X
X
X
X
X
As appropriate for particular tumor types (local testing).  For 
example, include alpha-fetoprotein for patient with HCC.
Hematology
X
X
X
X
X
X
X
X
X
See Appendix 2
Coagulation
X
See Appendix 2. Perform at baseline and as clinically 
indicated.
Fibrinogen
X
See Appendix 2. Perform at baseline and as clinically 
indicated when CRP and/or ESR are elevated from baseline
TSH and free T4
X
X
See Appendix 2.  Perform at baseline, C3D1, every 2 cycles 
thereafter, and more frequently as clinically indicated.
C3a complement
X
X
X
See Appendix 2. Perform at baseline, C2D1, C3D1, every 
other cycle thereafter and more frequently as clinically 
indicated.
C-ANCA/
P-ANCA
X
See Appendix 2. Perform at baseline and more frequently as 
clinically indicated.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 14
LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 28 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D15
D1
D15
D1
D15
D1
D15
Troponin-I
X
See Appendix 2. Perform at baseline and more frequently as 
clinically indicated.
Clinical chemistry 
X
X
X
X
X
X
X
X
X
See Appendix 2
C-reactive protein
X
X
X
X
X
ESR
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
See Appendix 2. Perform at specified timepoint and as 
clinically indicated.
Pregnancy test
X
See Instructions
Applies only to women of childbearing potential
Note:  during study treatment, perform monthly or as 
required per local regulations and/or institutional 
guidelines.
See Appendix 2
Tumor imaging/
assessment
X
X
See 
Instructions
Perform locally according to RECIST 1.1, using the same 
method at each assessment
Perform as scheduled, even if study treatment is delayed or 
omitted, except when deemed not feasible in the opinion of 
the investigator because of the patient’s clinical status
Note:  After C1D1, perform Q8W (±7 days) according to 
RECIST 1.1 for the first year, until a discontinuation 
criterion is met. If radiologic imaging verifies an initial 
assessment of PD, apply RECIST 1.1 with confirmatory 
scan for disease progression (Section 9.1.1).
If the patient is still on study treatment after 1 year, 
perform tumor imaging approximately every 12W.
Sample collection
See Appendix 4 for pharmacodynamics, pharmacokinetics, 
immunogenicity, pharmacogenetics, tumor tissue, and other 
biomarkers.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 15
LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 28 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D15
D1
D15
D1
D15
D1
D15
Administer 
LY3434172
X
X
X
X
X
X
X
X
LY3434172 will be administered as an IV infusion over 
approximately 60 minutes, depending on dose level (doses 
<100 mg may require bolus IV injection administration over 
approximately 5 to 10 minutes).  A 4-hour observation period 
following the end of LY3434172 administration will occur in 
Cycles 1 to 3.
Abbreviations:  AE = adverse event; C = Cycle; C-ANCA = cytoplasmic antineutrophil cytoplasmic antibody; CRP = C-reactive protein; CTCAE = Common 
Terminology Criteria for Adverse Events; D = day; ECG = electrocardiogram; ECHO = echocardiogram; ECOG PS = Eastern Cooperative Oncology Group 
performance status; ESR = erythrocyte sedimentation rate; free T4 = free thyroxine; HCC = hepatocellular carcinoma; ICF = informed consent form; IV = 
intravenous; P-ANCA = perinuclear antineutrophil cytoplasmic antibody; PD = progressive disease; Q = every; RECIST 1.1 = Response Criteria in Solid 
Tumors Version 1.1; TSH = thyroid stimulating hormone; W = weeks.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 16
LY3434172
Table JZEA.2
Baseline and On-Study Treatment Schedule of Activities (Cohort A7 and A8)
Baseline
(Day 
Relative to 
C1D1)
Cycle = 21 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D8
D1
D8
D1
D1
Procedure
Informed consent
X
ICF must be signed before any protocol-specific procedures 
are performed
Inclusion/exclusion 
criteria
X
Medical history
X
Including assessment of preexisting conditions and historical 
illnesses
Cancer treatment 
history
X
Record prior anticancer therapy
Concomitant 
medication
X
X
At baseline, record prior and concurrent medications
Record all premedication, supportive care, and 
concomitant medication continuously at each visit and
throughout the study.
Physical 
examination
X
X
X
X
X
X
X

D1 visit should be completed by a physician.

Should include palpable tumor measurement.
Vital signs 
X
X
X
X
X
Measure vital signs (height (at baseline), weight, 
temperature, blood pressure, pulse rate, oxygen 
saturation, and respiration rate) as follows (±5 minutes):
In Cycles 1 through 3:
up to 15 minutes prior to each LY3434172 infusion
every 15 minutes during each LY3434172 infusion
at the end of each LY3434172 infusion
A 4-hour observation period (See Section 5.1.1 and 7.4)
following the end of LY3434172 administration will occur in 
Cycles 1 to 3.
every 30 (±5) minutes for the first hour and every
60 (±5) minutes thereafter during the 4-hour observation 
period.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 17
LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 21 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D8
D1
D8
D1
D1
In Cycle 4 and beyond, if the patient has not 
experienced an infusion-related reaction or other 
infusion-related AE:
up to 15 minutes prior to each LY3434172 infusion
at least once during each LY3434172 infusion
at the end of each LY3434172 infusion
AE collection
X
X
Collect continuously at each visit and throughout the study
CTCAE Version 5.0
ECOG PS
X
X
X
X
X
X
X
During study treatment, perform 3 days prior to D1 of each 
cycle.
ECHO
X
See 
instructio
ns
Perform locally, at baseline, at Cycle 4 Day 1, and as 
clinically indicated.
ECG
See Appendix 4 for ECG collection instructions
Blood tumor 
markers
X
X
X
X
X
As appropriate for particular tumor types (local testing).  For 
example, include alpha-fetoprotein for patients with HCC.
Hematology
X
X
X
X
X
X
X
See Appendix 2
Coagulation
X
See Appendix 2. Perform at baseline and as clinically 
indicated.
Fibrinogen
X
See Appendix 2.  Perform at baseline and as clinically 
indicated when CRP and/or ESR are elevated from baseline
TSH and free T4
X
X
See Appendix 2.  Perform at baseline, C3D1, every 2 cycles 
thereafter, and more frequently as clinically indicated.
C3a complement
X
X
X
See Appendix 2. Perform at baseline, C2D1, C3D1, every 
other cycle thereafter and more frequently as clinically 
indicated.
C-ANCA/P-ANCA
X
See Appendix 2. Perform at baseline and more frequently as 
clinically indicated.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 18
LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 21 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D8
D1
D8
D1
D1
Troponin-I
X
See Appendix 2. Perform at baseline and more frequently as 
clinically indicated.
Clinical chemistry 
X
X
X
X
X
X
X
See Appendix 2
C-reactive protein
X
X
X
X
X
ESR
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
See Appendix 2. Perform at specified timepoint and as 
clinically indicated.
Pregnancy test
X
See Instructions
Applies only to women of childbearing potential
Note:  during study treatment, perform monthly or as 
required per local regulations and/or institutional 
guidelines
See Appendix 2
Tumor imaging/
assessment
X
X
See 
Instructio
ns
Perform locally according to RECIST 1.1, using the same 
method at each assessment
Perform as scheduled, even if study treatment is delayed or 
omitted, except when deemed not feasible in the opinion of 
the investigator because of the patient’s clinical status.
Note:  After C1D1, perform Q6W (±7 days) according to 
RECIST 1.1 for the first year, until a discontinuation 
criterion is met. If radiologic imaging verifies an initial 
assessment of PD, apply RECIST 1.1 with confirmatory 
scan for disease progression (Section 9.1.1).
If the patient is still on study treatment after 1 year, 
perform tumor imaging approximately every 12W.
Sample collection
See Appendix 4 for pharmacodynamics, pharmacokinetics, 
immunogenicity, pharmacogenetics, tumor tissue, and other 
biomarkers.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Baseline
(Day 
Relative to 
C1D1)
Cycle = 21 days
Instructions
Cycle 1
(±3 days)
Cycle 2
(±3 days)
Cycle 3
(±3 days)
Cycle 4-n
(±3 days)
28
7
D1
D8
D1
D8
D1
D1
Administer 
LY3434172
X
X
X
X
LY3434172 will be administered as an IV infusion over 
approximately 60 minutes, depending on dose level (doses 
<100 mg may require bolus IV injection administration 
approximately 5 to 10 minutes). A 4-hour observation period 
following the end of LY3434172 administration will occur in 
Cycles 1 to 3.
Abbreviations:  AE = adverse event; C = Cycle; C-ANCA = cytoplasmic antineutrophil cytoplasmic antibody; CTCAE = Common Terminology Criteria for 
Adverse Events; D = day; ECG = electrocardiogram; ECHO = echocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; 
ESR = erythrocyte sedimentation rate; free T4 = free thyroxine; HCC = hepatocellular carcinoma; ICF = informed consent form; IV = intravenous; P-
ANCA = perinuclear antineutrophil cytoplasmic antibody; PD = progressive disease; Q = every; RECIST 1.1 = Response Criteria in Solid Tumors 
Version 1.1; TSH = thyroid stimulating hormone; W = weeks.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 20
LY3434172
Table JZEA.3.
Poststudy Treatment Schedule of Activities (All Parts)
Follow-Up Visit
(±7 days)
Instructions
Short-Terma
Long-Term
(Q90D)b
Visit
30-Day
60-Day
90-Day
801
802
803
804 to 8XX
Procedure
Pregnancy test
X
X
X
Perform pregnancy test for women of childbearing potential
ECG
See Appendix 4 for ECG collection instructions
Physical examination
X
Including weight and vital signs (temperature, blood pressure, pulse rate, 
oxygen saturation, and respiration rate)
Concomitant medication
X
AE collection
X
X
X
X
CTCAE Version 5.0.  During the 30-, 60-, and 90-day follow-up visits, 
collect all AEs/SAEs.  Thereafter, collect only SAEs related to study 
treatment or protocol procedures
ECOG performance status
X
Tumor imaging/assessment 
X
For patients who discontinue study treatment without objectively measured 
PD, continue to perform tumor assessment and imaging every 8 to 12 weeks 
according to the standard-of-care
Collection of survival 
information
X
X
X
X
In-person office visits are not required; the site may confirm survival by 
contacting the patient directly via telephone or other means of 
communication (for example, email)
Collection of poststudy-
treatment anticancer therapy 
information
X
X
X
X
Discontinuation from study treatment must occur prior to introduction of the 
new agent
Hematology
X
See Appendix 2
Clinical Chemistry
X
See Appendix 2
Coagulation
X
See Appendix 2
Sample collection
See Appendix 4 for pharmacodynamics, pharmacokinetics, immunogenicity, 
pharmacogenetics, tumor tissue, and other biomarkers.
Abbreviations:  AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events (NCI 2017); ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group (Oken et al. 1982); F/U = follow-up; PD = progressive disease; PK = pharmacokinetics; SAE = serious adverse event.
a
Short-term follow-up begins when the patient and investigator agree that the patient will discontinue study treatment and ends on the day of the 90-day (±7 
days) follow-up visit.  
b
Long-term follow-up begins when short-term follow-up is completed and continues until death, study withdrawal, or the patient is lost to follow-up.  No 
follow-up procedures will be performed for a patient who withdraws informed consent unless he or she has explicitly provided permission and consent.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 2 1
L Y 3 4 3 4 1 7 2
T a bl e J Z E A . 4.
C o nti n u e d A c c e s s S c h e d ul e of A cti viti e s
C o nti n ue d Access 
Tre at me nt
C o nti n ue d Access
F oll o w - up Visits
a
I nstr ucti o ns:
Visit 
3 0- D a y
6 0- D a y
9 0- D a y
5 0 1- 5 X X
9 0 1
9 0 2 
9 0 3
D 1
D 1 5
L Y 3 4 3 4 1 7 2 
Sc he d ule
All
Q 2 W
Pr oce d ure
A E c ollecti o n
X
X
X  
X  
X
As part of A E c ollecti o n, m o nit or vital si g ns a n d perf or m sta n dar d 
la b orat or y tests ( he mat ol o g y, c he mistr y, uri nal ysis, a n d pre g na nc y 
testi n g) at t he sa me fre q ue nc y as t he st u d y treat me nt peri o d (see Ta ble 
J Z E A.1 a n d Ta ble J Z E A. 2 ).  All la b orat or y tests d uri n g t he c o nti n ue d 
access peri o d will be perf or me d i n t he l ocal la b orat ories o nl y.
P K, I G a n d 
e x pl orat or y 
h y perse nsiti vit y
I n t he e ve nt of a n I R R, bl o o d sa m ples will be c ollecte d f or P K, I G a n d 
e x pl orat or y h y perse nsiti vit y a nal yses at t he f oll o wi n g ti me p oi nts, as 
cl ose as p ossi ble t o:  (i) t he o nset of t he I R R, (ii) t he res ol uti o n of t he 
I R R, a n d (iii) 3 0 [ ± 3] da ys f oll o wi n g t he I R R.
 
 
 
 
A d mi nister 
L Y 3 4 3 4 1 7 2
X  
X
A b bre viati o ns:  A E = a d verse e ve nt; D = da y ; I G = i m m u n o ge nicit y; I R R = i nf usi o n-r elate d reacti o n; P K = p har mac o ki netics.
a
C o nti n ue d access f oll o w -u p be gi ns w he n t he patie nt a n d t he i n vesti gat or a gree t hat t he patie nt will n o l o n ger c o nti n ue treat me nt i n t he c o nti n ue d acc ess 
peri o d a n d lasts a p pr o xi matel y 3 0 da ys.   
C CI


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
3. Introduction
3.1.
Study Rationale
T-cells play a central role in immune response to tumors.  However, tumors have adopted 
multiple mechanisms to evade host immune surveillance.  One of the key mechanisms is 
programmed cell death protein-1 receptor (PD-1) and its ligands, programmed death ligand 1 
(PD-L1) and programmed death ligand 2 (PD-L2), coinhibitory molecules (immune checkpoints) 
that suppress T-cell-mediated immune responses. Both PD-L1 and PD-L2 ligands can bind to 
the PD-1 receptor on T-cells.  
In addition, PD-L1 can also bind to B7-1 on T-cells.  These PD-1 axis interactions lead to 
suppression of T-cell activation.  In a variety of tumors, PD-L1 is frequently over-expressed by 
tumor cells. Blocking the PD-1/PD-L1 axis has been shown to remove this suppression and 
reinvigorate T-cell activation (Zou et al. 2016).
While anti-PD-1 and anti-PD-L1 antibodies have demonstrated durable clinical responses in 
multiple tumor indications, only a subset of patients benefit from these treatments with room for 
further improvement (Jenkins et al. 2018). Eli Lilly & Company (Lilly) has designed a novel 
approach using a bispecific antibody (BsAb) to target both PD-L1 and PD-1.  Such a BsAb will 
be capable of blocking all interactions of the PD-1/PD-L1 axis (PD-1 with PD-L1 and PD-L2, 
B7-1 with PD-L1) whereas anti-PD-1 does not block PD-L1-B7-1 interactions and anti-PD-L1 
does not block PD-L2-PD1 interactions. In addition, in vitro experiments have demonstrated 
that LY3434172 can bridge cells engineered to express PD-1 and those that express PD-L1; the 
clinical relevance of bridging will be assessed in this study.
The goal of this study is to establish the safety of the PD-1/PD-L1 bsAb as monotherapy in 
patients with advanced solid tumors. If the product has an acceptable clinical safety profile and 
shows sufficient activity, additional studies and/or cohorts may be added to determine a safe 
dose alone or in combination with other anticancer therapies.
3.2.
Background
While inhibitors of both PD-1 and PD-L1 have shown clinical activity and manageable safety 
profiles as monotherapy in a variety of tumor types, their efficacy in various tumor types could 
potentially be improved (Wu et al. 2015).  The possible benefit of targeting the PD-1/PD-L1 
pathway with another immune checkpoint inhibitor, which can further augment the response, is 
an important area of interest.
LY3434172 is a human bsAb (effectorless IgG1-Fc) consisting of two different sets of light and 
heavy chains. One pair of the heavy-light chain is a human immunoglobulin G1 (IgG1) variant 
that binds PD-L1 and the other pair is a human IgG1 variant that binds PD-1. 
The in vitro and in vivo biological properties of LY3434172 were characterized in nonclinical 
pharmacology studies.  LY3434172 blocks all interactions of the programmed death (PD) axis: 
PD-1 binding to PD-L1 and PD-L2 ligands, as well as B7-1 binding to PD-L1.  In vitro, 
LY3434172 can bridge a PD-L1 expressing target cell and a PD-1 expressing T-cell to enable 


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 23
LY3434172
T-cell activation that is superior to parental PD-1 and PD-L1 monoclonal antibodies (mAbs) or 
their combination.  Furthermore, LY3434172 demonstrates in vivo antitumor efficacy in 
humanized mouse model systems.  Collectively, LY3434172 fully blocks the PD-1 and PD-L1 
axes and more effectively releases immune inhibitory signals to promote T-cell activation and 
enhance antitumor efficacy.
The toxicity profile of LY3434172 was investigated in cynomolgus monkeys administered 
intravenous (IV) bolus doses of 0, 30, and 100 mg/kg twice weekly for 1-month (9 doses total;
Table JZEA.5).  LY3434172 binds to and antagonizes both human and monkey PD-1 and PD-L1 
with similar affinity and potency, establishing cynomolgus monkeys as a pharmacologically-
relevant species for toxicity testing. 
No mortality or significant clinical signs were observed and all animals survived to scheduled 
necropsy.  LY3434172-related clinical pathology changes at both doses were largely limited to 
minimal decreases in albumin with minimal to mild increases in globulins, compatible with an 
acute phase response.  LY3434172-related microscopic findings of minimal to marked
vascular/perivascular mononuclear cell infiltrates in multiple organs were observed in 14 of 16 
animals (7 at 30 mg/kg, 7 at 100 mg/kg).  The histological features, spectrum of affected organs, 
and distribution of microscopic findings at both dose levels were consistent with immune 
complex deposition secondary to an immune response to LY3434172.  Microscopic changes 
similar in appearance and location have been observed in preclinical studies for other 
biopharmaceuticals, and have been determined to be the result of an immune response to the 
therapeutic compound (Rojko et al. 2014).  Commonly affected organs included brain, heart, gall 
bladder, and organs of the reproductive and gastrointestinal tracts – a tissue/ organ spectrum 
which is also compatible with published reports (Heyen et al. 2014; Leach et al. 2014; Rojko et 
al. 2014; Husar et al. 2017; Kronenberg et al. 2017).  Immunohistochemical detection of granular 
deposits containing LY3434172, endogenous monkey immunoglobulin M (IgM) and 
immunoglobulin G (IgG), and/or complement C3 at sites of vascular lesions in many of the 
tissues tested provided definitive evidence of immune complex deposition in development of 
vascular/ perivascular infiltrates.
These findings are consistent with a Type III hypersensitivity response, which have been 
described in monkey studies for a number of therapeutic monoclonal antibodies (Heyen et al. 
2014; Leach et al. 2014; Rojko et al. 2014; Husar et al. 2017; Kronenberg et al. 2017).
Importantly in this case, a high incidence of anti-drug antibody (ADA) in LY3434172-treated 
animals and detection of granular deposits in affected tissues of representative animals provided 
robust evidence of immune complex disease.  In monkeys, immune complex-related 
vascular/perivascular inflammation is commonly found in varied organs/tissues such as the 
gastrointestinal tract, gall bladder, heart, and tissues of the reproductive tract, consistent with the 
organs affected in this study.  Based on historical examples, there is low potential risk for clinical 
translation of both preclinical immunogenicity (IG) and immune complex-related pathology
(Husar et al. 2017; Kronenberg et al. 2017).  
No LY3434172-related effects were observed on other standard toxicology endpoints in the 
study with the exception of heart rate (HR) increases noted in a subset of animals affected by 


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 24
LY3434172
vasculitis (Table JZEA.5).  While transient increases in HR were observed in the light 
photoperiod, most pronounced changes (with maximal increases ranging up to +23 bpm) were 
observed during the dark phase of the recording period (100 mg/kg only) on Day 5.  By Day 22, 
HR changes of similar magnitude (with maximal changes up to +39 bpm) were observed at both 
dose levels, with evidence of a carryover effect during predose recording (+17 to 19 bpm)
indicative of a reduced but sustained heart rate effect.  No changes in QTc or any waveform 
abnormalities were noted in any animal on either day.
As the vascular findings were considered adverse to the animals in the study at both 30 mg/kg 
and 100 mg/kg, a no-observed-adverse-effect level (NOAEL) was not identified for this study.
The proposed starting dose of 3 mg every two weeks (Q2W) has a multiple of ≥2,000-fold based 
on dose and projected maximum observed drug concentration (Cmax), and a >10,000-fold
multiple based on projected average drug concentration (Cav) over the dose interval, compared to 
the lowest dose of 30 mg/kg tested in monkeys in the 1-month repeat-dose study.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Table JZEA.5.
Summary of 1-month Repeat-Dose Monkey Toxicity Study with 
LY3434172
Study Type
Study 
Number
Species
Number
Doses 
(mg/kg)
Route
Duration
Parameters
Evaluated
Low Dosee
High Dosee
1-month 
GLP toxicity
study 
20134606
Monkey
Cynomolgus
4/sex/group
0a, 30, 100
IV
twice-weekly 
for 1 month (9 
total doses)
Mortality, BW, clin 
signs, phys, temp, resp, 
neuro, ophthal, ECG, 
TK/ADA, immunob, 
clin pathc, pathd
30 mg/kg IV
(Exposure Day 29:  
mean AUC0-96hr= 
103000 µg*hr/mL; 
C0=1540 µg/mL)
100 mg/kg IV
(Exposure Day 29:  
mean AUC0-96hr= 
400000 µg*hr/mL;  
C0=5610 µg/mL)
Microscopic 
findings:
Cardio-
vascular 
findings:
LY3434172-related adverse findings included minimal to marked vascular/perivascular mononuclear 
or mixed cell infiltrates in 14 of 16 animals (7 animals at 30 mg/kg, 7 animals at 100 mg/kg). The 
histological nature, tissue locations, and distribution of the lesions were consistent with an indirect 
ADA response to LY3434172 and resultant immune complex deposition and damage. Subsequent 
investigative work demonstrated immune complex deposition in lesions from multiple tissues/ organs 
from a representative subset of affected animals
Increases in heart rate (HR) were observed in several animals on Day 5 (100 mg/kg; up to +23 bpm) 
and Day 22 (30 and 100 mg/kg; up to +39 bpm), most notably pronounced during the dark 
photoperiod.  Changes on Day 22 were elevated at predose (+17-19 bpm) and were of a similar 
magnitude in both dose groups during the dark photoperiod.
Abbreviations:  ADA = anti-drug antibody; mean AUC0-96hr = average area under the plasma concentration-time 
curve from time zero to 96 hours for both males and females; BW = body weight; clin = clinical; mean 
C0 = mean maximal plasma concentration for both males and females extrapolated to t=0 time point; 
ECG = electrocardiogram; immuno = immunophenotyping; IV = intravenous; neuro = neurological evaluations; 
NOAEL = no-observed-adverse-effect level; NK = natural killer; ophthal = ophthalmic examinations; 
path = pathology; phys = physical examinations; resp = respiratory rate and depth; temp = body temperature; 
TK = toxicokinetics (plasma LY3434172).
a
Vehicle control group.  
b
Peripheral blood immunophenotyping.
c
Hematology, coagulation, cytokines, complement, clinical chemistry, and urinalysis.
d
Organ weights, gross pathology, histopathology, immunohistochemistry.
e
An NOAEL was not identified in this study due to indirect adverse effects in animals that were driven by an 
immune response to LY3434172.
Additional information pertaining to nonclinical efficacy and safety may be found in Section 4.2 
of the Investigator’s Brochure (IB).  
Information pertaining to nonclinical pharmacokinetics (PK) and metabolism may be found in 
Section 4.1 of the IB. 
3.3.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated adverse events (AEs) of LY3434172 are to be found in the 
Investigator’s Brochure (IB).  


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
4. Objectives and Endpoints
Table JZEA.6 shows the objectives and endpoints of the study.
Table JZEA.6.
Objectives and Endpoints
Objectives
Endpoints
Primary
To assess the safety and tolerability of LY3434172, thereby 
identifying a RP2D of LY3434172, administered to patients 
with advanced solid tumors.

DLTs

Safety (including but not limited to): TEAEs, 
DLT-equivalent toxicities, SAEs, deaths, and 
clinical laboratory abnormalities per CTCAE 
(Version 5.0)
Secondary
To assess the PK in patients with solid tumors of 
LY3434172.

AUC, Cmin and approximate Cmax of 
LY3434172 
To assess  preliminary antitumor activitya of LY3434172 

ORR

DOR

TTR

DCR 
Tertiary/Exploratory
To characterize tumor tissue and blood biomarkers relevant 
to LY3434172, including but not limited to immune 
cells/immune functioning, mechanism of action of study 
drugs, cancer-related pathways, and disease state

Results of biomarker analyses

Clinical outcomes
To explore the association between biomarkers and dose, 
concentrations and clinical outcomes

Results of biomarker analyses

Clinical outcomes
To assess the IG of LY3434172 in patients with advanced 
solid tumors.

Relationship between TE ADA and safety

Relationship between TE ADA and LY3434172 
pharmacokinetics.
To assess PFS and OS of patients receiving LY3434172.

PFS

OS
Abbreviations: Cmax = maximum serum/plasma concentration; Cmin = minimum serum/plasma concentration; 
CTCAE = Common Terminology Criteria in Adverse Events; DCR = disease control rate; DLT = dose-limiting 
toxicity; DOR = duration of response; IG = immunogenicity; ORR = objective response rate; OS = overall 
survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors; 
RP2D = recommended Phase 2 dose; SAE = serious adverse event; TEAE = treatment-emergent adverse event; 
TE ADA = Treatment-emergent anti-drug antibodies; TTR = time-to-response.
a
Response assessment using RECIST 1.1 and RECIST 1.1 with confirmatory scan for disease progression.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
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L Y 3 4 3 4 1 7 2
5. St u d y  D e si g n
5. 1.
O v er all D e si g n
St u d y  J 1 E-M C -J Z E A (J Z E A) is a m ult ice nter, n o nra n d omize d, o pe n -label , first i n h u ma n
P hase 1 st u d y  in pat ient s wit h a d va nce d s o li d t u m ors.
P hase 1 st u d y  will assess t he safet y a n d t olera bilit y of L Y 3 4 3 4 1 7 2 , a d mi nistere d as a 
m o n ot hera p y  in pat ient s wit h select a d va nce d s o li d t u m ors (see Fi g ure J Z E A. 1 ).  L Y 3 4 3 4 1 7 2 
will be a d mi nistere d as a n I V b o l us i njecti o n f or d oses less t ha n 1 0 0 m g (a p pr o xi matel y 5 t o 
1 0 mi n utes) a n d f or d oses ≥1 0 0 m g, I V i nf usi o n o ver a p pr o xi matel y 6 0 mi n utes. Patie nts 
e nr o lle d i nt o C o h orts A 1 t hr o u g h A5 / 6 will be a d mi nistere d L Y 3 4 3 4 1 7 2 o n a Q 2 W d ose 
sc he d ule.  C o h ort A6 is a n o pti o nal c o h ort t hat ma y be e x pl ore d at a d ose n ot e xcee di n g 1 0 0 0 m g 
of  L Y 3 4 3 4 1 7 2 base d o n safet y, P K, a n d p har mac o d y na mic data . D o se escalati on will be dri ve n 
b y m o difie d t o xi cit y pr o ba bility i nter val 2 ( m T PI 2 ) met h o d ( G u o et al. 2 0 1 7), e nr olli n g at least 
t hree patie nts per c o h ort.  F urt her disc ussi o n o n d ose escalat i on is e x plai ne d i n Secti on 5. 1. 1 .
T o facilitate a t h or o u g h safet y  e val uati on a n d e x pl orati o n of P K a n d p har m ac o d y na mics effects
of t he e ver y t w o wee k ( Q 2 W) d osi n g sc he d ule ( C o h orts A 1 t o A 6 ) will be e x pl ore d .  Once 
d ose -li mitin g t o xi cit y ( D L T) perio d is c o m plete d f or res pecti ve C o h orts A 1 t o A 5 / 6 u p t o
a p pr o xi matel y 1 2 t o 1 5 a d diti o nal pat ient s ma y be a d de d t o t w o d ose le vels selecte d fr o m t hese 
c o h orts (see Fi g ure J Z E A. 1 ). After e val uat i n g P K/p har mac o d y na mic data fr o m t hese c o h orts, 
a n y d oses fr o m t he d ose escalat i on ra n ge c o ul d be use d i n or der t o c o ver t he e nt ire pre dicte d 
bi o l ogicall y  effecti ve d ose ( B E D) a n d all o w f or u ncertai nt y ar o u n d it (see S ecti o n 5. 5).   F or 
e xa m ple, if 3 0 0 m g is a d ose le vel selecte d, a d di tio nal pat ient s ma y be e nr o lle d i n parallel wi t h 
C o h ort A 5 after C o h ort A 4 has cleare d D L T. 
I n a d diti on, a n e ver y t hree-wee k (Q 3 W ) d osi n g sc he d ule ( C o h orts A 7 a n d A 8) will be e val uate d 
t o all o w f or fle xi bility f or fut ure c o m bi nat i ons wit h sta n dar d -of -care a ge nts t hat ma y use a Q 3 W 
d ose re gi me n.  T he Q 3 W d osi n g sc he d ule c o ul d be i nit iate d as C o h orts A7 a n d A8 i n parallel 
wi t h t he e nr o ll me nt of  a d ditio nal pat ient s e nr olle d i nt o t w o d ose le vels o f t he Q 2 W sc he d ule, 
res pecti vel y. 
O n g o i n g safety re vie ws bet wee n t he Lill y a n d t he i n vesti gat ors will be c o n d ucte d after 
c o mplet i on of  t he D L T perio d f or eac h c o h ort t o e ns ure it is safe t o c o nti n ue with t he ne xt 
d ose -escalat i on c o h ort.
I nteri m a nal yses will be c o n d ucte d at t he e n d of d ose escalati on fr om C o h orts A 1 t o A 5/ 6 at 
c o mplet i on of D L T peri o d acr oss t hese c o h orts.  T he rec o m me n de d P hase 2 d ose ( R P 2 D) will be 
i de ntifie d after fi nal a nal yses u p o n c o mplet i on of t his P hase 1 st u d y .  If L Y 3 4 3 4 1 7 2 has a n 
acce pta ble cli nical safet y pr ofile a n d s h o ws s ufficie nt acti vity,  a d ditio n al  st u dies a n d/ or c o h orts 
ma y be a d de d t o deter mi ne a safe d ose al o ne or i n c o m bi nat i on wi t h ot her a ntica ncer t hera pies.  
As n ote d i n Secti o n 9. 8 , P D -L 1 e x pressi o n a n d ot her bi o mar kers will be e val uate d, a n d ma y 
i nfl ue nce e nric h me nt strate gies f or s u bse q ue nt st u dies a n d/ or c o h orts.
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J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 2 8
L Y 3 4 3 4 1 7 2
5. 1. 1.
D o s e E s c al ati o n 
T he first patie nt will be e nr olle d i n C o h ort A 1 a n d treate d acc or di n g t o a Q 2 W d osi n g re gi me n 
(see Fi g ure J Z E A. 1 ).  
 
 
 
 
 
  A D L T 
o bser vat i on peri o d of  2 8 da ys ( 4 2 da ys i n C o h ort A 1) will a p pl y  t o all p atie nts o n t he Q 2 W 
d osi n g re gi me n i n s u bse q ue nt c o h orts.  O n g oi n g safet y re vie ws bet wee n t he Lill y cli nical 
researc h p h ysicia n/cli nical researc h scie ntist ( C R P/ C R S) a n d t he i n vest i gat ors will be c o n d ucte d 
d uri n g a n d u p o n c o m plet i on of t he D L T peri o d f or eac h c o h ort, t o e ns ure it is safe t o c o nti n ue 
wi t h t he ne xt d ose-escalat i on c o h ort.
After t he first patie nt i n C o h ort A 1 recei ves t he first d ose of L Y 3 4 3 4 1 7 2, t here will be a dela y of 
1 wee k bef ore t he sec o n d patie nt recei ves L Y 3 4 3 4 1 7 2 t o all o w f or s af et y o bser vati o n.  I n all 
s u bse q ue nt c o h orts, t he first patie nt i n eac h d ose le vel will be o bser ve d f or a p pr o xi matel y 
2 4 h o urs bef ore a n y a d dit i onal patie nts are treate d; n o a d dit i onal dela ys are re q uire d f or 
s u bse q ue nt patie nts i n t he sa me c oh ort.
P ati e nts i n C o h orts A 2, A 3, A 4, A 5, a n d A 6 ( o pti o nal), res pecti vel y, 
 
pr o vi de d safet y is 
esta blis he d i n t he prece di n g c o h orts. O nce D L T peri o d of 2 8 da y s f or Q 2 W, e xce pt C o h ort A 1 
wi t h 4 2 da y D L T, is c om p lete d f or res pecti ve d ose le vels wit hi n C o h orts A 1 t o A 5 / A 6, t wo d ose 
C CI
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J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 2 9
L Y 3 4 3 4 1 7 2
le vels, yet t o be deter mi ne d b ut will be selecte d fr o m t hese c o h orts, ca n be e x pa n de d bet wee n 1 2 
a n d 1 5 patie nts i n t otal. P har mac o ki ne tic, p har mac o d y na mic a n d safet y data e val uate d d uri n g 
t he c o urse of t he d ose escalat i on will  be use d t o select t hese t w o d ose le vels. T he p ur p ose of 
e x pa n di n g t o a d ditio nal 1 2 -1 5 pati e nts is t o f urt her i nf or m safet y, P K a n d p har m ac o d y na mics.  
T hese c o h orts will c o nt i n ue t o e nr oll w hile i nteri m a nal ysis ( I A) is o n g oi n g.
C o h orts of patie nts will be treate d wit h escalat i n g d oses of L Y 3 4 3 4 1 7 2 acc or di n g t o a n m T PI- 2 
met h o d u ntil t he criteria f or reac hi n g t he ma xi m u m- t olerate d d ose ( M T D) are met. F or s o me 
i m m u n o-o nc ol o g y  c o mp o u n ds t hat ha ve ma na gea ble safet y pr ofiles a n d d o n ot reac h a M T D, 
a d ditio nal  inf or m atio n s uc h as p har mac o d y na mic mar kers ma y  be hel pf ul i n deter mi ni n g t he 
a p pr o priate R P 2 D ( A gra wal et al. 2 0 1 6; Parc h me nt et al. 2 0 1 6).  
A Q 3 W d osi n g re gi me n will be e x pl ore d i n C o h orts A 7 , A8 at d oses yet t o be deter mi ne d.  T he 
Q 3 W d osi n g re gi me n will use t he L Y 3 4 3 4 1 7 2 d ose a nt ici pate d t o ha ve dr u g e x p os ure si milar t o 
t wo selecte d Q 2 W d os e l e vels w here a d di tio n al  patie nts were e nr olle d. T h e Q 3 W d osi n g 
sc he d ule c o ul d be i nitiate d as C o h orts A7 a n d A8 i n parallel with t he Q 2 W e x pa nsi o n
res pecti vel y.  
5. 2.
N u m b er of P ati e nt s
E nr oll me nt i n eac h c o h ort will be a dj uste d if nee de d t o all o w a de q uate assess me nt of safet y a n d 
preli mi nar y a nt itu m or acti vit y at t he L Y 3 4 3 4 1 7 2 R P 2 D.  Pla n ne d e nr o ll me nt is as f oll ows:
A p pr o xi matel y  1 5 t o 2 0 patie nts will be e nr olle d i n Q 2 W d ose escalati o n, a p pr o xima t ely 1 2 t o 
1 5 a d ditio n al  pat ient s ma y be a d de d t o t wo d ose l e vels selecte d fr o m C o h orts A 1 t o A 5 /A 6 after 
selecte d d ose l e vel has cleare d t he D L T peri o d f or a de q uate assess me nt of safety a n d e x plor ati o n 
of  P K a n d p har mac o d y na mic effects. T he a d dit i on al  patient s f or t he t w o selecte d d ose le vels ca n 
be e nr olle d i n parallel t o d ose escalat i on i n Q 2 W as l o n g as t he d ose le vel e x pl ore d has cleare d 
D L T.
I n parallel, patient s will be e nr olle d i n Q 3 W c o h orts (A 7 a n d A 8 ) t o allo w fle xi bili t y for 
f ut ure c o m bi nati ons wit h sta n dar d -of -care a ge nts. T he sa m ple size of Q 3 W de pe n ds pri maril y 
o n P K pr ofiles a n d cli nical c o nsi derat i ons .  A mi ni m u m of t hree patie nts will be e nr olle d i n eac h 
c o h ort.
5. 3.
E n d of St u d y D efi niti o n
E n d of t he st u d y  is t he date of t he last visit or last sc he d ule d pr oce d ure s h o w n i n t he Sc he d ule o f 
Act i vities ( Secti o n 2 ) for t he last patie nt.
5. 4.
S ci e ntifi c R ati o n al e f or St u d y D e si g n
See Secti o ns 3. 1 a n d 3. 3 .
 
 
 
 
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6. Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all the following criteria:
[1]
Melanoma, NSCLC, squamous cell carcinoma of the head and neck (SCCHN), 
urothelial cancer, gastric cancer, colorectal cancer, biliary tract cancer, anal cancer, 
nasopharyngeal cancer, esophageal cancer, SCLC, ovarian cancer, mesothelioma, 
pan-tumor MSIhi solid tumors, hepatocellular carcinoma, merkel cell cancer, 
cutaneous squamous cell carcinoma, endometrial cancer, breast cancer, cervical 
cancer, thyroid cancer, salivary cancer, and prostate cancer who have received at least 
one line of standard systemic therapy for their respective tumor type in the metastatic 
setting with progressive locally advanced or metastatic disease and that is not 
amenable/resistant to approved standard-of-care therapy. Prior anti-PD-1 and anti-
PD-L1 allowed if they received another therapy immediately prior to this study or 
there has been a lapse of approximately ≥90 days from prior therapy. If patients 
received prior anti-PD-1 or anti-PD-L1, the following criteria need to be met:
a) did not experience a toxicity that led to permanent discontinuation of prior 
anti-PD-1, anti-PD-L1, or other immunotherapy.
b) have completely recovered to at least his or her previous baseline level prior 
to screening from any clinically significant AEs that occurred during prior 
immunotherapy.
c) did not experience any of the following irAEs during prior anti-PD-1, anti-
PD-L1, or other immunotherapy:

a Grade ≥3 irAE

any grade neurologic or ocular irAE

any grade immune-related pneumonitis or cardiomyopathy
Patients with an endocrine AE are permitted to enroll if they are stably maintained on 
appropriate replacement therapy and are asymptomatic
d) did not require immunosuppressive agents, other than corticosteroids for the 
management of an AE, did not experience recurrence of a Grade ≥3 AE if 
rechallenged, and does not currently require maintenance doses of >10 mg 
prednisone (or equivalent) per day.
[2]
have at least one measurable lesion assessable using standard techniques by Response 
Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Eisenhauer et al. 
2009).  Bone metastases are not considered measurable.


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[3]
are able and willing to provide the protocol required biopsies from a newly obtained 
core or excisional pre-treatment biopsy of a tumor lesion and a newly obtained core 
or excisional biopsy collected during the study treatment period (See Section 9.8.1).  
(Note: An archived tumor sample also will be requested, if not restricted by local 
regulations).
[4]
have an Eastern Cooperative Oncology Group performance status of 0 or 1
(Oken et al. 1982).
[5]
have discontinued all previous treatments for cancer for at least 14 days and 
recovered from the acute effects of therapy.  Patients must have discontinued from 
previous treatments, as shown below:
Previous Treatmenta
Length of Time Prior to First Dose of Study 
Treatment
Cytotoxic therapies or targeted agents that are 
small-molecule inhibitors
14 days
Mitomycin-C or nitrosoureas
>42 days
Biologic agents (excludes anti-PD-1, anti-PD-L1)
14 days
Radiotherapy
28 days
Limited field radiotherapy (i.e. <25% bone 
marrow affected)
14 days
Major surgery, excluding biopsy
Patients with recent major surgery must have 
recovered, in the opinion of the investigator, from 
the toxicity and/or complications from the 
intervention before starting therapy.
a
At the discretion of the investigator, patients with hormone-refractory prostate cancer who are 
stable on gonadotropin-releasing hormone agonist therapy and patients with breast cancer who are 
stable on antiestrogen therapy (for example, an aromatase inhibitor) may continue that treatment while 
enrolled in this study.
[6]
have adequate organ function, as defined below, with all screening laboratory 
assessments performed within 28 days of treatment initiation.
System
Laboratory Value
Hematologic
ANC
1.5 × 109 cells/L
Platelets
100 × 109/L
Hemoglobin
9 g/dL
At the discretion of the investigator, patients may 
receive erythrocyte transfusions to achieve this 
hemoglobin level; however, study treatment may not 
begin until 2 days after erythrocyte transfusion and after 
confirmation of hemoglobin 9 g/dL.
aPTT
1.5 × ULN


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Hepatic
Total bilirubin
1.5 × ULN OR
<3.0 x ULN for patients who have Gilbert’s syndrome
ALT and AST
2.5 × ULN OR
5 × ULN if the liver has tumor involvement
Renal
Serum creatinine OR
Calculated creatinine clearance 
1.5 × ULN OR
50 mL/min
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; aPTT = activated 
partial thromboplastin time; AST = aspartate aminotransferase; HCC = hepatocellular carcinoma; 
ULN = upper limit of normal.
Note: Adequate organ function should be confirmed within 7 days prior to first dose on Cycle 1 Day 1.
[7]
are, at the time of screening, 18 years old or of an acceptable age to provide 
informed consent according to local regulations, whichever is older
[8]
Men with partners of childbearing potential or women with childbearing 
potential must agree to use a highly effective contraceptive method of birth 
control (Appendix 1) during study treatment and for at least 6 months 
following the last dose of study drug.   
[9]
Women of childbearing potential must have a negative serum pregnancy test 
documented within 7 days prior to initiation of treatment (see Appendix 9).
[10] have given written informed consent/assent prior to any study-specific procedures
[11] have an estimated life expectancy of 12 weeks, in the judgment of the investigator
[12] are reliable and willing to make themselves available for the duration of the study and 
are willing to follow study procedures
6.2.
Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
[13] Are currently enrolled in a clinical study involving an investigational product or any 
other type of medical research judged not to be scientifically or medically compatible 
with this study.
[14] Have a serious concomitant systemic disorder that, in the opinion of the investigator, 
would compromise the patient’s ability to adhere to the protocol, such as the 
following:
a.
Human Immunodeficiency Virus (HIV) positive patients (HIV 1 and/or 2; 
screening not required) are excluded unless they are well controlled on highly 
active antiretroviral therapy (HAART) therapy with
-
No evidence of AIDS-defining opportunistic infections within the last 2 years, 
and
-
CD4 count > 350 cells/µL


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b. active hepatitis B or C virus infection according to local standards (screening not 
required) (e.g., with no evidence of known positive hepatitis B surface antigen or 
known positive hepatitis C antibody and quantitative hepatitis C RNA greater 
than the lower limit of detection of the assay).
c.
current active tuberculosis
d. active infection requiring systemic therapy
e.
prior or second concurrent primary malignancies that, in the judgment of the 
investigator and the Lilly CRP/CRS, may affect the interpretation of results.  
Patients with carcinoma in situ of any origin and patients with prior malignancies 
who are in remission and whose likelihood of recurrence is very low (such as 
basal cell carcinoma), as judged by the Lilly CRP/CRS, are eligible for this study
f.
Active or suspected autoimmune disease (e.g., autoimmune vasculitis, 
autoimmune myocarditis) or any illness that could compromise the immune 
system (e.g., prior organ transplant) within the past two years, or a syndrome or 
condition that requires systemic corticosteroids or immunosuppressive agents.  
Patients at risk of vascular adverse events, such as those with a history of angiitis, 
arteritis, or hypersensitivity vasculitis as an adverse reaction to medication, for 
example, are not eligible.
This criterion does not apply to patients with:  (i) vitiligo, alopecia, or type I 
diabetes mellitus; (ii) residual hypothyroidism due to an autoimmune condition 
requiring only hormone replacement; or (iii) psoriasis not requiring chronic 
systemic immunosuppressive treatment within the past 2 years, not expected to 
recur in the absence of an external trigger.
g. use of escalating or chronic supraphysiologic doses of corticosteroids or 
immunosuppressive agents (such as, exceeding 10 mg/day of prednisone or 
equivalent).  Use of topical, ophthalmic, inhaled, and intranasal corticosteroids 
permitted.
This criterion does not apply to patients with:  (i) resolved childhood 
asthma/atopy or who require intermittent use of bronchodilators or local 
corticosteroid injections; (ii) hypothyroidism that is stable on hormone 
replacement; (iii) Raynaud’s syndrome; or (iv) Sjogren’s syndrome.
h. bowel obstruction, history or presence of inflammatory enteropathy or extensive 
intestinal resection (hemicolectomy or extensive small intestine resection, either 
condition with chronic diarrhea), Crohn’s disease, ulcerative colitis, or chronic 
diarrhea
i.
evidence of (i) interstitial lung disease that is symptomatic or may interfere with 
the detection or management of suspected drug-related pulmonary toxicity; 
(ii) active, noninfectious pneumonitis; or (iii) history of noninfectious 
pneumonitis that required corticosteroid therapy


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j.
moderate or severe cardiovascular disease, such as the following:
(i)
presence of cardiac disease, including a myocardial infarction or any 
other arterial thrombotic event, blood clots  not limited to deep vein 
thrombosis, cerebrovascular accident or transient ischemic attack  
within 6 months prior to enrollment; unstable angina pectoris; New 
York Heart Association Class III/IV congestive heart failure; aneurysm 
of major vessels or heart; left ventricular ejection fraction <50% 
(evaluation based on institutional lower limit of normal); or 
uncontrolled hypertension
(ii)
severe, moderate, or clinically significant valvulopathy; documented 
major electrocardiogram (ECG) abnormalities that, in the judgment of 
the investigator, are clinically significant (for example, symptomatic 
arrhythmias or arrhythmias requiring treatment; myocardial infarction 
within the last 3 months; or mean QTc 470 ms calculated using 
Fredericia’s correction and confirmed by triplicate ECG).
(iii)
Previous cardiotoxic cancer treatment associated with type 1 damage 
such anthracyclines (e.g., daunorubicin, doxorubicin, epirubicin, 
idarubicin) and previous thoracic radiotherapy with a field involving the 
heart
[15] Have symptomatic central nervous system (CNS) malignancy or metastasis 
(screening not required).  Patients with treated CNS metastases are eligible for this 
study if they are not currently receiving corticosteroids and/or anticonvulsants to treat 
CNS metastases, and their disease is asymptomatic and radiographically stable for at 
least 30 days.
[16] Unresolved toxicities from prior anticancer therapy, including immune-related 
adverse event (irAE), that have not resolved to the baseline levels prior to starting the 
prior anticancer therapy.
[17] have received a live vaccine within 30 days before the first dose of study treatment.  
Examples of live vaccines include, but are not limited to, the following:  measles, 
mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette–Guérin, and 
typhoid vaccine.  Seasonal influenza vaccines for injection are generally killed virus 
vaccines and are allowed; however, intranasal influenza vaccines (for example, 
FluMist®) are live attenuated vaccines and are not allowed.
[18] are pregnant, breastfeeding, or planning to become pregnant during the study or 
within 6 months of the last dose of LY3434172.
[19] have a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the study, interfere with the patient’s 
participation for the full duration of the study, or is not in the best interest of the 
patient to participate, in the opinion of the treating investigator
[20] have current or history of allergy or hypersensitivity to study drug components


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6.3.
Lifestyle Restrictions
There are no specific lifestyle restrictions for this protocol.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) within the 
28-day baseline-screening period may be rescreened.  Individuals may be rescreened up to 
2 times after initial screening.  The interval between rescreening should be at least 1 week.  Each 
time rescreening is performed, the individual must sign a new informed consent form (ICF) and 
will be assigned a new identification number.  All required tests (see Section 2) must be repeated 
for patients who are rescreened in a new 28-day baseline-screening period.
Repeating laboratory tests (including ECGs) that did not meet eligibility criteria during the 
28-day baseline-screening period does not constitute rescreening.  However, laboratory tests may 
not be repeated more than twice. 


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 3 7
L Y 3 4 3 4 1 7 2
7. Tr e at m e nt
7. 1.
Tr e at m e nt A d mi ni st er e d
L Y 3 4 3 4 1 7 2 will be a d mi nistere d as a n I V i nf usi on o ver a p pr o xi matel y 6 0 mi n utes, de pe n di n g o n 
d ose l e vel ( d oses < 1 0 0 m g m a y re q uire b o l us I V i nf usi on , a p pr o xi matel y o ver 5 t o 1 0 mi n utes ).  
A 4 -h o ur o bser vat i on peri o d f oll owi n g t he e n d of L Y 3 4 3 4 1 7 2 a d mi nistrati o n will occ ur i n 
C ycles 1 t o 3.
T he i n vest i gat or or his/ her desi g nee is res p o nsi ble f or t he f oll owi n g:

e x plai ni n g t he c orrect use of t he dr u g(s) a n d t he pla n ne d d urati o n o f eac h 
i n di vi d ual’s treat me nt t o t he pati e nt a n d st u d y site pers o n nel

verif yi n g t hat i nstr ucti o ns are f o ll owe d pr o perl y 

mai ntai ni n g acc urate rec or ds of st u d y  dr u g dis pe nsi n g a n d c ollect i on

at t he e n d of t he st u d y ret ur ni n g all u n use d me dicati o ns t o Lill y, or its desi g nee, 
u nless Lill y  a n d sites ha ve a gree d all u n use d me dicati o ns are t o be destr o ye d b y 
t he site, as all o we d b y lo c al  la w
7. 1. 1.
P a c k a gi n g a n d L a b eli n g
All st u d y dr u g will be pr o vi de d b y Lill y.  Cli nical st u d y materials will be la bele d acc or di n g t o 
t he c o u ntr y’s re g ulat or y r e q uire me nts.
C CI


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LY3434172
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be assigned to receive LY3434172 in this study.  
An interactive web-response system (IWRS) will be used to dispense study drugs and to ensure 
that the correct number of patients is assigned to each cohort.
No dose escalations (i.e. to the next cohort) can occur without prior discussion of clinical data 
and agreement with the responsible Lilly CRP/CRS. 
If investigators have eligible patients who have consented concurrently, more than the assigned
patients may be entered at a particular dose level if accrual has not ceased due to excessive 
toxicity.  This enrollment procedure is allowed because of the advanced disease state of this 
patient population and the screening involved in defining eligibility.  This event should be 
approved by the Lilly CRP/CRS following discussions with the investigators.
7.2.1.
Selection and Timing of Doses
The doses will be administered at approximately the same times on each day.  The actual time of 
all dose administrations will be recorded in the electronic case report form (eCRF).
A cycle is defined as an interval of 28 days (Q2W regimen) and 21 days (Q3W regimen) as 
shown in Table JZEA.7.  A delay of a cycle due to holiday, weekend, bad weather, or other 
unforeseen circumstances will be permitted for a maximum of 7 days and not counted as a 
protocol deviation. The reason for the delay should be documented on the eCRF.
The first study treatment will be administered within 7 days after the patient is assigned to a 
treatment cohort.  There should be a minimum of 14 days between doses of study drug for all 
cohorts in Q2W schedule and 21 days between doses of study drug for the Q3W schedule.
However, if there is a delay due to holiday, weekend, bad weather, or other unforeseen 
circumstances, a flexibility of ±3 days is permitted.
A patient may continue to receive LY3434172 until he or she meets one or more of the specified 
reasons for discontinuation (see Section 8).
7.2.2.
Dose Escalation 
Safety data, in particular AEs, will be the primary criteria for the dose escalation.  In addition, if 
available at the time of dose escalation decision, PK (for example, approximate Cmax, minimum 
plasma concentration (Cmin), area under the concentration (AUC) versus time curve, 
pharmacodynamics results) will be used as secondary/supporting data for dose escalation.  No 
dose escalation can occur without prior discussion and agreement between the investigator(s) and 
the Lilly CRP/CRS; the decision will be documented in writing.  
7.2.2.1.
Dose Escalation Method
An mTPI-2 method will be used to identify an RP2D for LY3434172, taking into consideration 
available PK and pharmacodynamic data from previous dose levels. Each cohort in this study 
will enroll at least three patients.


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Like the 3+3 design, the mTPI-2 method incorporates prespecified escalation rules.  In contrast, 
the mTPI-2 method is based on quantitative models that incorporate uncertainty into the decision 
rules, thereby allowing more precise RP2D selection.  If three or six patients are enrolled in a 
cohort, the escalation rule parallels a traditional 3+3 design.  However, it allows flexible number 
of patients in a cohort.  For example, with two DLTs per six patients enrolled, the mTPI-2 would 
recommend staying at the current dose, as analogy to one DLT per three patients enrolled in 3+3 
design; therefore, it allows more patients for a more precise estimate of the DLT rate at this dose 
level. 
Appendix 8 provides the mTPI-2 escalation rules for any cohort size up to 20 patients.
Following a discussion between the Lilly CRP/CRS and the investigators, a more conservative
dose selection may be applied to the next cohort (for instance, if PK/pharmacodynamic data
suggest that further dose increase would not be expected to yield additional benefit). For
example, if the rule indicates “E” to escalate, the dose may stay at the current dose level, be 
de-escalated to a lower level, or escalation may cease. In the mTPI-2, the cohort size is not fixed.  
However, each cohort in this study will contain a minimum of three patients, unless the 
escalation rules dictate that the dose should be de-escalated (“D” or “DU”). Doses can be 
escalated, de-escalated, and re-escalated following the rules in Appendix 8. If the dose decision 
was “DU,” the dose cannot be re-escalated to that level.  This study is designed to identify a dose 
level with a dose-limiting target toxicity rate of 30%.  The mTPI-2 method considers an 
equivalence interval (EI) around the target toxicity rate. For this study, the EI is elicited to be 
(25%, 35%), resulting in the rules in Appendix 8.
Intermediate and/or higher dose as well as alternative schedules of administration will be
explored if deemed necessary after discussion between Lilly and investigators and taking into
account patient safety and PK/pharmacodynamics data. If necessary, additional patients may be 
enrolled to further assess PK/pharmacodynamics or tolerability.
7.2.2.2.
Dose-Limiting Toxicity Determination
A DLT is defined as any of the events listed in Table JZEA.8, if both the following criteria are 
met:

the event occurs during the DLT observation period (Cycle 1, 42 days) for Cohort A1, 
(Cycle 1, 28 days) for Cohorts A2 to A5 (A2 to A6 if Cohort A6 is opened), (Cycle 1 and 
2, 42 days) for Cohorts A7 and A8, and

the event is clinically significant and definitely, probably, or possibly related to 
LY3434172, in the opinion of the investigator.
Patients in Cohorts A1 to A5/6, A7, and A8 who experience a DLT in Cycle 1 will be 
discontinued from study treatment.


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Table JZEA.8.
Dose-Limiting Toxicity
Hematologic toxicity

Grade 3 thrombocytopenia associated with clinically significant bleeding and requiring platelet transfusion or 
Grade 4 thrombocytopenia of any duration

Grade 3 febrile neutropenia

Grade 3 anemia requiring a blood transfusion

Other Grade 4 toxicity lasting >7 days, excluding toxicities listed in Section 7.2.2.1
Nonhematologic toxicity – nonlaboratory

Grade 4 irAE, except as stated otherwise below

Grade 3 colitis or noninfectious pneumonitis 

Other Grade 3 irAE, excluding colitis or pneumonitis, that:
o
does not downgrade to Grade 2 within 3 days after onset of the event despite optimal medical 
management including corticosteroid therapy, or
o
does not downgrade to Grade 1 or the patient’s baseline level within 14 days after onset of the event

Grade 3 pneumonitis or Grade 2 pneumonitis that does not show clinical improvement within 3 days after 
initiation of optimal medical management including corticosteroids therapy, which is then treated as Grade 3

Grade 3 toxicity despite optimal supportive care (e.g., nausea, vomiting, and diarrhea)

Grade 3 fatigue lasting >7 days

Grade 3 hypertension despite maximal medical therapy
Nonhematologic toxicity – laboratory/investigations

Other Grade 3 or 4 laboratory value lasting >14 days or requiring medical intervention

ALT or AST:
o
>8 × ULN, if the patient does not have HCC or liver metastasis

2-fold above the patient’s baseline value that lasts >7 days, if the patient has HCC or liver metastasis and 
had ALT or AST >3.0 × ULN at baseline

>3 × ULN with concomitant bilirubin >2 × ULN, in the absence of cholestasis

Total bilirubin >3 × ULN

≥Grade 3 amylase or lipase that is associated with symptoms or clinical manifestations of pancreatitis
Other hematologic or nonhematologic toxicity

Grade 5 toxicity (i.e. death)

≥Grade 3 electrolyte abnormality that lasts >72 hours unless the patient has clinical symptoms, in which case 
all Grade 3+ electrolyte abnormality regardless of duration should count as a DLT. 

Toxicity deemed by the investigator and the Lilly CRP/CRS to be dose limiting, such as:
o
toxicity that is possibly related to study treatment and requires discontinuation of the patient from the 
study at any time during Cycle 1, or
o
persistent Grade >2 toxicities causing a delay of >14 days in initiating Cycle 2 
o
Grade 3 vasculitis
Abbreviations:  AE = adverse event; ALT = alanine transaminase; AST = aspartate transaminase; CRP = clinical 
research physician; CRS = clinical research scientist; HCC = hepatocellular carcinoma; irAE = immune-related 
adverse event; IV = intravenous; ULN = upper limit of normal. 
Potential DLTs that are adverse events, which are reasonably anticipated AEs for concomitant 
medication should be reviewed by the treating investigator and Lilly CRP/CRS before final 
determination as a DLT.  Review and discussion may include additional participating 
investigators.  Such review may determine that confounding factors render the case to be not 
evaluable for the purposes of dose selection.  


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7.2.2.2.1. Events That Are Not Considered to Be DLTs
The following events will not be considered to be DLTs:

Toxicity that is clearly and directly related to the primary disease or to another etiology

Grade 3 endocrine disorder (thyroid, pituitary, and/or adrenal insufficiency), if both the 
following criteria are met:
o
the disorder is manageable with or without systemic corticosteroid therapy and/or 
hormone replacement therapy, and 
o
the patient is asymptomatic

Grade 3 inflammatory reaction attributed to a local antitumor response (such as, 
inflammatory reaction in the lymph nodes or at sites of metastatic disease)

Any grade vitiligo or alopecia

First occurrence of Grade 3 infusion-related reaction (IRR) during infusion of LY3434172, if 
both of the following criteria are met:
o
the patient did not receive corticosteroid prophylaxis, and
o
the Grade 3 IRR resolves within 6 hours with appropriate clinical management
o
If symptoms reappear, the event would be considered a DLT.
o
If this first occurence is anaphylaxis of any grade, the event would be considered a DLT.

Grade 3 or 4 neutropenia meeting both of the following criteria are met:
o
is not associated with fever or systemic infection, and
o
improves by at least 1 grade within 7 days

Grade 3 or 4 lymphopenia
It should be recognized that for patients who have received prior immune therapy, including 
checkpoint inhibitor therapy, there is the potential for delayed manifestation of serious irAEs 
such as colitis, hepatitis, pneumonitis, and endocrinopathies.  Patients manifesting potential 
delayed irAEs should receive prompt evaluation and treatment.  
7.2.2.2.2 DLT-Equivalent Toxicities
A DLT-equivalent toxicity (ET) is an AE that meets the DLT criteria as defined above and 
occurs in any cycle other than the DLT assessment period (28 days for Q2W schedule and 42 
days for Q3W schedule).  In addition to the DLT assessment period, available safety data beyond 
the DLT assessment period may also be taken into consideration prior to a decision to advance to 
the next dose level or the determination of the RP2D.
7.2.2.3.
Recommended Phase 2 Dose Determination
The RP2D will be chosen following discussion between the Lilly CRP/CRS and the investigators 
based on consideration of the totality of the data during interim analyses and upon completion of 
Phase 1, including but not limited to LY3434172 dose adjustments, AEs, chronic intolerance, PK 
and pharmacodynamic data, and irAEs.  If LY3434172 has an acceptable clinical safety profile 
and shows sufficient activity, additional studies and/or cohorts may be added to determine a safe 
dose alone or in combination with other anti-cancer therapies.  PD-L1 expression and other 


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biomarkers will be evaluated, and may influence enrichment strategies for subsequent studies 
and/or cohorts.
7.3.
Blinding
This is an open-label study.
7.4.
Dose Modification
No dose modification is allowed during the DLT observation period (Cycle 1).  See Section 8 for 
discontinuation criteria.  See Section 7.6.1.1 for the definition of DLT-evaluable patients.
After the DLT observation period (Cycle 1), doses of the study drug may be delayed or 
discontinued to manage specific AEs or other toxicities.  Dose reductions are not permitted.  All 
dose modifications should be documented, including the approach taken and a clear rationale for 
the need for modification.
The investigator must assess whether the toxicity is at least possibly due to study treatment and 
apply the dose-modification guidelines.  Investigators are encouraged to consult Lilly for 
additional guidance.
If a patient requires a dose delay, study treatment should be resumed within 1 cycle, if possible 
and appropriate.  If study treatment cannot be resumed within 1 cycle, every effort should be 
made to restart on the first day of the next cycle.  In rare circumstances, a delay of >28 days may 
be permitted before permanent treatment discontinuation, as long as the patient demonstrates 
clinical benefit, does not have objective progression, and is recovering from the toxicity.  Such 
circumstances must be discussed with the Lilly CRP/CRS.
Adverse events of immune-related etiology are expected because of the study drug’s mechanism 
of action and may occur shortly after the first dose or several months after the last dose.  Study 
treatment must be withheld if the patient experiences a drug-related toxicity or a severe or life-
threatening AE.  Dose reductions are not permitted.
A 4-hour observation period following the end of LY3434172 administration will occur in 
Cycles 1 to 3. During observation period, patients treated with LY3434172 should be closely 
monitored for signs and symptoms indicative of an infusion-related reaction by medical staff 
from the start of the infusion, in an area where emergency medical resuscitation equipment and 
other agents (epinephrine, prednisolone, or equivalents, etc.) are available.  LY3434172 infusion-
related reactions will be defined according to the Common Terminology Criteria for Adverse 
Events (CTCAE), version 5.0 definition of IRRs.
Table JZEA.9 presents instructions for management of infusion-related reactions associated with 
LY3434172.


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Table JZEA.9.
Management of Infusion-Related Reactions (IRR)
Grade
Management
2
First occurrence  
Immediately and permanently discontinue treatment if hypersentivity reaction is 
due to anaphylaxis of any grade.
Stop the infusion for other infusion-related reactions.
1.
If resolved to baseline or Grade 1 within 1 hour after stopping the infusion
a.
restart the infusion at 50% of the original rate (e.g., reduce from 
100 mL/hr to 50 mL/hr)
2.
If NOT resolved to Grade 0 or 1 within 1 hour after stopping the infusion:
a.
delay study treatment until the symptoms resolve in ≤48 hours, and 
b.
premedicate prior to the next scheduled dose. Premedication should be 
administered 1.5 hours (±30 minutes) prior to the LY3434172 infusion 
with diphenhydramine (or other antihistamine), acetaminophen (or other 
antipyretic), steroids, etc., at the discretion of treating physician.
Second occurrence  
Immediately and permanently discontinue study treatment
3 or 4
Immediately and permanently discontinue study treatment except for situation 
below:
Patients who experience Gr3 IRR that resolves within 6 hours may continue on 
study treatment.  For subsequent infusions, the patient should be premedicated 
1.5 hours (±30 minutes) prior to the LY3434172 infusion with diphenhydramine 
(or other antihistamine), acetaminophen (or other antipyretic), steroids, etc., at the 
discretion of treating physician.
American Society of Clinical Oncology (ASCO) guideline (Brahmer et al. 2018) for irAE 
management (including use for corticosteroids) will guide criteria for dose delays and 
discontinuations if the patient experiences a potential irAE considered at least possibly related to 
LY3434172. 
Because of the potential for rapid and serious sequelae associated with irAEs, early intervention 
with corticosteroids is encouraged, concurrent with further diagnostic medical evaluations for 
possible nonimmune-related causes of AEs.  The treatment plan should always include a 
thorough workup of the issue to rule out other potential etiologies such as infection.  Local 
standards may supersede the guidelines provided in table below if deemed appropriate by the 
investigator.  If a patient experiences an irAE that is not listed in this table, consult the Lilly
CRP/CRS to discuss appropriate management.
Other corticosteroid options can be given at equivalent doses.  Corticosteroids should be tapered 
over 1 month once symptoms improve to Grade ≤1, and study treatment should not be restarted 
until corticosteroid tapering is complete.  During corticosteroid use, use prophylactic antibiotics 
to prevent opportunistic infections.


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Table JZEA.10.
Dose Modification Guidelines and AE Management for Toxicities At Least Possibly Related to Study 
Drug
SOC
Toxicity
CTCAE Grade and/or Symptomsa
Treatment Planb
Grade
Symptoms
Endocrine
Thyroid issues
If asymptomatic with 
TSH <0.5 × LLN or 
>2 × ULN
Continue study treatment; perform free T4 in 
subsequent cycles.
If symptomatic
Start thyroid replacement therapy and/or 
medical management and continue study 
treatment
For Grade 3 hyperthyroidism, withhold study 
treatment until hyperthyroidism improves to 
Grade 1
For Grade 4 hyperthyroidism, discontinue 
study treatment
Endocrine
Hypotension, altered mental 
status, headache, fatigue, 
hyperglycemia
For endocrine issues 
other than thyroid 
issues (for example, 
hypophysitis)
For Grade 2, withhold study treatment and 
administer prednisone 1 to 2 mg/kg/day
Resume study treatment when symptoms 
resolve and the patient is stable on hormone 
replacement therapy
For Grade 3 or 4, discontinue study treatment
For severe adrenal crisis, give stress dose of 
IV corticosteroids with mineralocorticosteroid
Gastrointestinal
Diarrhea, Abdominal pain, 
Blood in stool, Colitis
2
Withhold study treatment, give anti-diarrheal 
medication, and check etiology
If the event continues for >5 days despite the 
use of antidiarrheal medications, start 
prednisone 0.5 to 1 mg/kg/day
Resume study treatment after the event 
resolves to Grade 1


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SOC
Toxicity
CTCAE Grade and/or Symptomsa
Treatment Planb
Grade
Symptoms
Gastrointestinal
Diarrhea, 
Ileus, 
Perforation, 
Colitis
3
Withhold study treatment and administer 
prednisone 1 to 2 mg/kg/day (no 
corticosteroids if possible perforation)
If the event persists >3 days despite use of 
corticosteroids, add a nonsteroidal 
immunosuppressive agent and discontinue 
study treatment.c
Resume study treatment after the event 
resolves to Grade 1
Discontinue study treatment if Grade 3 
persists
For Grade 4, discontinue study treatment
Hepatobiliary
Transaminitis, elevated bilirubin
2
AST or ALT between 
2.5 × ULN and
5 × ULN, or 
TB between 1.5 × 
ULN and 3 × ULN
Withhold study treatment and administer 
prednisone 1 to 2 mg/kg/day
Resume study treatment after symptoms 
resolve to Grade 1
3
AST or ALT >5 × 
ULN, or 
TB >3 × ULN
Discontinue study treatment and administer 
IV methylprednisolone 2 to 4 mg/kg/day 
If the event continues for >3 days despite 
corticosteroids, add a nonsteroidal 
immunosuppressive agentc
Nervous system
Weakness, paresthesia (for 
example, Guillain–Barre 
syndrome or myasthenia gravis)
Moderate symptoms 
with no impact on ADL
Withhold study treatment until symptoms 
resolve.
2 irAE 
Impact on ADL
Discontinue study treatment.  Give appropriate 
medical intervention and prednisone 1 to 
2 mg/kg/day.
Instructions if vasculitis 
suspected: New onset loss of 
motor function
Follow management guidelines above as 
clinically indicated
Consult neurologist/ rheumatologist, 
preferably with vasculitis expertise


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SOC
Toxicity
CTCAE Grade and/or Symptomsa
Treatment Planb
Grade
Symptoms
Respiratory
Pneumonitis
1
Consider withholding study treatment and 
monitoring for radiographic improvement.
2
Mild to moderate 
symptoms
Withhold study treatment and administer 
prednisone 1 to 2 mg/kg/day
Resume study treatment after the event 
resolves to Grade 1
3
Severe
Discontinue study treatment and administer:
o IV methylprednisolone 2 to 4 mg/kg/day 
and 
o prophylactic antibiotics
If the event remains at Grade 3 for >2 days 
despite corticosteroids, add a nonsteroidal 
immunosuppressive agentc
Instructions if vasculitis
suspected: Hemoptysis, 
appearance of new lung nodules 
or rapidly progressing 
respiratory failure.
Consult pulmonologist/rheumatologist with 
vasculitis expertise in addition to following 
management instructions above.
Signs of additional nodules and infiltrates 
(compared to baseline) from thoracic CT 
scans could be suggestive of vasculitis (See 
Section 9.4.2.1)
Cardiac
Myocarditis, cardiac function 
abnormalities (for example. 
dysrhythmia, valvular 
abnormalities)
1
Discontinue study treatment and administer
o IV methylprednisolone 2 to 4 mg/kg/day 
o Consider immunosuppressives without 
immediate response to steroids (for 
example, mycophenolate, infliximab, or 
anti-thymocyte globulin)
Consult with cardiology immediately and; if 
available, transfer to cardiac care unit


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SOC
Toxicity
CTCAE Grade and/or Symptomsa
Treatment Planb
Grade
Symptoms
Renal and urinary
Elevated creatinine, decreased 
urine output, blood in urine, 
edema, nephritis
1
<1.5 x baseline
Continue study treatment
2-3
1.5 × ULN< × 6 × 
ULN or >1.5 × 
baseline
Withhold study treatment and administer 
prednisone 0.5 to 1 mg/kg/day
Resume study treatment after the event 
resolves to Grade 1
If elevations persist for >7 days or worsen, 
follow the guidelines for a Grade 4 event
4
>6 × ULN
Discontinue study treatment and administer 
prednisone 1 to 2 mg/kg/day.
Instructions if vasculitis 
suspected:
Elevated creatinine, decreased 
urine output, blood in urine, 
RBC casts, proteinuria
Creatinine: 
1.5 × ULN< × ≤6 × 
ULN or >1.5 × 
baseline
Proteinuria: >1+ on 
dipstick or regular 
urine analyses
Follow management guidelines above as 
clinically indicated
Repeat creatinine and proteinuria and RBC 
casts in 7 days and if levels of creatinine and 
proteinuria still elevated and RBC casts still 
present, consult nephrologist and/or 
rheumatologist, preferably with vasculitis 
expertise. See Section 9.4.2.1.
Skin
Rash, pruritus
Moderate rash (diffuse, 
30% BSA)
Withhold study treatment
For rash on <10% of the patient’s BSA, 
administer intermediate or high-potency 
topical corticosteroid
For rash on 10%-30% of the patient’s BSA, 
administer systemic corticosteroids
Resume study treatment if the rash improves 
to mild (localized) and the corticosteroid 
dose is <7.5 mg/day
Instructions if vasculitis 
suspected:
Palpable purpura, skin ulcers
Follow management guidelines above as 
clinically indicated
Consult dermatologist/rheumatologist 
preferably with vasculitis expertise.
Confirmation of vasculitis with skin punch 
biopsy required ( See Section 9.4.2.1)


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SOC
Toxicity
CTCAE Grade and/or Symptomsa
Treatment Planb
Grade
Symptoms
Skin
Stevens–Johnson syndrome, 
toxic epidermal necrolysis, 
necrosis, bullous or hemorrhagic 
lesions
Discontinue study treatment and administer 
prednisone 1 to 2 mg/kg/day
Ophthalmological
Eye disorders (for example, 
uveitis, episcleritis)
2
Consider topical steroids (for example, 1% 
prednisolone); temporarily discontinue study 
treatment until ophthalmology consult and 
administer
o Oral or IV methylprednisolone 2 to 
4 mg/kg/day 
Instructions if vasculitis 
suspected: blurred vision, vision 
loss, periorbital swelling
Follow management guidelines above as 
clinically indicated
Consult ophthalmologist/rheumatologist 
preferably with vasculitis expertise.
See Section 9.4.2.1.
Abbreviations: ADL = activities of daily living; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BSA = body surface area; CRP = clinical 
research physician; CTCAE = Common Terminology Criteria for Adverse Events, version 5.0; irAE = immune-related adverse event; IV = intravenous; 
LLN = lower limit of normal; SOC = system organ class; TB = total bilirubin; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
a
If symptoms of grade is not specified, use CTCAE version 5.0 definitions; otherwise, use the definitions provided in this table.
b
Discontinuation of study treatment is permanent; resumption of study treatment is not allowed. If a toxicity does not resolve to Grade 0-1 or if the 
corticosteroid dose cannot be reduced to 10 mg/day of prednisone or equivalent within 12 weeks, consult with the Lilly CRP about discontinuing study 
treatment. In cases where corticosteroids are used, they should be appropriately tapered.
c
Immunosuppressive refers to infliximab or cyclophosphamide.


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7.5.
Preparation/Handling/Storage/Accountability
Investigators should consult the study drug information provided in the Pharmacy Manual.  
7.6.
Treatment Compliance
The study medication will be administered only at the investigational site by the authorized study 
site personnel.  As a result, treatment compliance is ensured.  
7.6.1. Evaluable Patients
7.6.1.1
DLT-Evaluable Patients in Phase 1 Dose Escalation
Dose escalation refers to Cohort A1 to A5 or Cohort A1 to A6 (if Cohort A6 is opened).
A patient will be DLT evaluable if he or she experiences a DLT during the DLT observation 
period and has received at least one dose of study drug.
If a patient does not experience a DLT during the DLT observation period, he or she will be DLT 
evaluable if he or she receives all assigned doses of study drug(s) during the DLT observation 
period
Patients who receive all doses of study drug but discontinue from study treatment before the end 
of the DLT observation period will be considered DLT evaluable for the assessment of a dose 
level, provided it can be documented that the patient did or did not experience a DLT within the 
DLT observation period.
Patients who are not DLT evaluable may be replaced to ensure that enough patients complete the 
DLT observation period at each dose level, unless accrual to that cohort has stopped due to a 
DLT.
A patient may be deemed non-evaluable for assessment of a dose level in the event the patient 
experiences an AE which would meet DLT criteria, and furthermore has been determined 
through discussion between investigator and Lilly CRP/CRS to most likely be related to a 
concomitant medication or a prior line of immune therapy (in the case of irAEs) due to 
previously established linkage.
To ensure collection of adequate PK or biomarker data, patients who complete the DLT 
observation period but who do not have a valid PK or biomarker assay result may be replaced, 
upon consultation with the investigator(s) and the Lilly CRP/CRS, unless accrual to that cohort 
has stopped because of a DLT.  Patients who are replaced for purposes of the PK or biomarker 
analysis are still considered DLT evaluable.
7.7.
Concomitant Therapy
Appendix 5 describes medications, treatments, and drug classes that are restricted or prohibited 
for use during the study treatment period, including exceptions and conditions.  There are no 
prohibited therapies during the post discontinuation follow-up period.  Patients who, in the 
opinion of the investigator, require the use of any of the prohibited treatments for clinical 


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management should be discontinued from the trial.  Patients may receive other supportive 
therapy that the investigator deems to be medically necessary.
In general, medications or live vaccinations specifically prohibited in the exclusion criteria are 
not allowed during the ongoing trial except with approval from Lilly CRP/CRS.
No other chemotherapy, systemic radiotherapy, immunotherapy, cancer-related hormone 
therapy, experimental drugs, herbal supplements intended to treat cancer will be permitted while 
the patients are on this study.  
Palliative radiation therapy to small areas of painful metastases that cannot be adequately 
managed with systemic or local analgesics is permitted after discussion with and agreement of 
the Lilly CRP/CRS. 
In addition, any disease progression requiring other forms of specific antitumor therapy will also 
necessitate early discontinuation from study treatment.  Appropriate documentation for all forms 
of premedication, supportive care, and concomitant medications must be captured on the eCRF.  
Replacement hormonal therapy initiated before study entry will be allowed.
Patients should receive full supportive care. The use of granulocyte-colony stimulating factor 
(G-CSF) is permitted at the discretion of the investigator based on ASCO (Smith et al. 2015) and 
European Society for Medical Oncology (Crawford et al. 2010) guidelines. 
If clinically indicated at any time during the study, erythropoietin and packed red blood cell 
transfusions may be used according to ASCO guidelines (Rizzo et al. 2008).  Prophylactic 
antibiotic treatment should be consistent with ASCO guidelines (Flowers et al. 2013).
All concomitant medications should be recorded throughout the patient’s participation in the 
study.
7.8.
Treatment after the End of Study
The end of study definition is defined in Section 5.3.  Investigators will continue to follow the 
schedule of activities provided in Section 2 until notified by Lilly that end of study has occurred.
7.8.1. Treatment after Study Completion
Study completion will occur following the final analysis of primary and secondary objectives, as 
determined by Lilly.  Investigators will continue to follow Schedule of Activities (Section 2) for 
all patients until notified by Lilly that study completion has occurred.
7.8.1.1.
Continued Access
Patients who are still on study treatment at the time of study completion may continue to receive 
study treatment if they are experiencing clinical benefit and no undue risks.  
The continued access period will apply to this study only if at least one patient is still on study 
treatment when study completion occurs.  Lilly will notify investigators when the continued 
access period begins.


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Lilly may allow patients to enroll in a “rollover” protocol to provide long-term continued access 
for patients enrolled in this study.  
Patients who are in short-term follow-up when the continued access period begins will continue 
in short-term follow-up until the 90-day short-term follow-up visit is completed.  Long-term 
follow-up does not apply.
Patients who are in long-term follow-up when the continued access period begins will be 
discontinued from long-term follow-up.
Figure JZEA.2.
Continued access diagram.


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8. Discontinuation Criteria
The reasons for treatment and study discontinuation and the dates of discontinuation will be 
collected for all patients.
Patients who discontinue during the study treatment period, whether or not they received study 
treatment, will have follow-up procedures performed as shown in the Schedule of Activities 
(Section 2).
If a patient withdraws informed consent, he or she must not be contacted unless he or she has 
explicitly provided permission and consent.  Lilly may continue to use previously collected 
medical research data prior to the withdrawal consistent with the original authorization.
8.1.
Discontinuation from Study Treatment
Patients will be discontinued from study treatment in the following circumstances: 

the patient is enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study.

the patient becomes pregnant during the study

the patient is significantly non-compliant with study procedures and/or treatment 
as described in Section 7.6

The patient experiences a DLT (see Section 7.2.2.2) during Cycle 1, a DLT-ET 
(see Section 7.2.2.2.2), or other unacceptable toxicity

the patient requires a dose delay of >28 days for Q2W schedule and >21 days for Q3W 
schedule, except as described in Section 7.4

the patient, for any reason, requires treatment with another therapeutic agent that 
has been demonstrated to be effective for treatment of the study indication.
Discontinuation from study treatment will occur prior to introduction of the new 
agent

the investigator decides that the patient should be discontinued from study 
treatment, for reasons such as but not limited to confirmed disease progression 
(see Section 9.1.1).

the patient requests to be discontinued from study treatment
Patients who are discontinued from study treatment will have follow-up procedures performed as 
shown in the Schedule of Activities (Section 2).


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Discontinuation of study treatment may be considered for patients who meet all of the following 
criteria:

have a confirmed complete response (CR), and

have received study treatment for at least 24 weeks, and

have received at least 2 cycles of study treatment beyond the date when the initial CR 
was declared.
8.1.1.
Discontinuation of Inadvertently Enrolled Patients
If Lilly or the investigator site identifies a patient who did not meet enrollment criteria and who 
was inadvertently enrolled, a discussion must occur between Lilly CRP/CRS and the investigator 
to determine if the patient may continue in the study.  If both agree that it is medically 
appropriate to continue ,the investigator must obtain documented approval from Lilly CRP/CRS
to allow the inadvertently enrolled patient to continue in the study with or without study 
treatment.  Safety follow-up is as outlined in the Schedule of Activities (Section 2).
8.2.
Discontinuation from the Study
Patients will be discontinued from the study in the following circumstances:

participation in the study needs to be stopped for medical, safety, regulatory, 
or other reasons consistent with applicable laws, regulations, and good clinical 
practice (GCP).

the patient becomes pregnant during the study.  See Section 9.1.1.3 regarding 
regulatory reporting requirements on fetal outcome and breast-feeding

the investigator decides that the patient should be discontinued from the study

the patient requests to be discontinued from the study

the patient’s legal representative requests that the patient be discontinued from 
the study
Patients who discontinue from the study early will have end-of-study procedures performed as 
shown in the Schedule of Activities (Section 2).
8.3.
Lost to Follow-Up
A patient would be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  Study site personnel are 
expected to make diligent attempts to contact patients who fail to return for a scheduled visit or 
who the site is otherwise unable to follow-up.


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9. Study Assessments and Procedures
Section 2 provides the Schedule of Activities for this study. 
Appendix 2 provides a list of the laboratory tests that will be performed for this study.
Appendix 4 provides the schedule for collection of samples in this study.
Unless otherwise stated in the following subsections, all samples collected for specified 
laboratory tests will be destroyed within 60 days of receipt of confirmed test results.  Certain 
samples may be retained for a longer period, if necessary, to comply with applicable laws, 
regulations, or laboratory certification standards.
9.1.
Efficacy Assessments
Tumor assessments will be performed for each patient at the times shown in the Schedule of 
Activities (Section 2). A secondary objective of the study is to document efficacy.
RECIST 1.1 (Eisenhauer et al. 2009) will be applied as the primary criteria for assessment of 
tumor response and disease progression.  Local tumor imaging (investigator assessment with site 
radiological reading) will be used.  
Computed tomography (CT) is the preferred imaging method for the majority of patients.  
Magnetic resonance imaging should only be used when CT is contraindicated or for imaging in 
the brain.  The same imaging technique should be used for a patient throughout the trial.  
Imaging should include the chest, abdomen, and pelvis.  Intravenous and oral contrast is required 
unless medically contraindicated.
At Study Baseline:

Must be performed within 28 days prior to the first dose of study drug.

Scans performed as part of routine clinical management are acceptable for use as initial 
tumor imaging if they are of diagnostic quality and performed within protocol-required 
time frame as described above.
During Study Treatment: 

Performed every 8 weeks (±7 days) for the 28-day cycle cohorts and every 6 weeks (±7 
days) for the 21-day cycle cohorts, by the investigator, with confirmatory assessment 
obtained at the next routine scheduled imaging time point (See Section 9.1.1).

Per RECIST v1.1, partial response (PR) or complete response (CR) should be confirmed 
by a repeat tumor imaging assessment, preferably at the next scheduled imaging visit, and 
not less than 4 weeks from the date the response was first documented.  Thus, for Study 
JZEA, tumor imaging for confirmation of response may be performed at the earliest 
four weeks after the first indication of response, or at the next scheduled scan, whichever 
is clinically indicated.

Continue to perform imaging until whichever of the following occurs first:
o
disease progression confirmed by the second radiographic examination


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o
the start of new anticancer treatment
o
withdrawal of consent
o
death
o
study completion
If radiologic imaging verifies an initial assessment of progressive disease (PD), apply 
RECIST 1.1 with confirmatory scan for disease progression (Section 9.1.1).
During the Poststudy Treatment Period:  Tumor assessments may continue for patients who 
are withdrawn from the study treatment for reasons other than disease progression every 8 to 
12 weeks depending on standard-of-care.
See Section 10.3.2 for definitions of the efficacy endpoints. 
9.1.1. RECIST 1.1 with Confirmatory Scan for Disease Progression
9.1.1.1.
Rationale for RECIST 1.1 with Confirmatory Scan for Disease 
Progression
Response to immunotherapy may differ from responses typically observed with cytotoxic 
chemotherapy, including the following (Wolchok et al. 2009; Nishino et al. 2013):

Response to immunotherapy may be delayed.

Response to immunotherapy may occur after PD by conventional criteria.

The appearance of new lesions may not represent PD with immunotherapy.

Stable disease while on immunotherapy may be durable and represent clinical benefit.
Therefore, to adequately characterize additional patterns of response and progression specific to 
patients treated with immunotherapy, which cannot be captured by conventional criteria such as 
RECIST 1.1, alternative measures of tumor assessment have been developed, such as RECIST 
1.1 with confirmatory scan for disease progression. Clinically stable patients may continue 
treatment until disease progression (per standard RECIST 1.1) is confirmed.  See Table JZEA.11
for further details and timing of confirmatory scans for PD.


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Table JZEA.11.
Summary of Response Assessment by RECIST, RECIST with 
Confirmatory Scan for PD, and irRC
Definition
Used in Study JZEA
Not Used in Study JZEA
RECIST v1.1
RECIST 1.1 with Confirmatory Scan for PD
irRC (Wolchock et al. 2009), 
irRECIST (Nishino et al. 
2013)
iRECIST (Seymour et al. 
2017)
New lesion
The presence 
of new lesion 
defines 
progression
The presence of new lesion defines progression
The presence of new lesion 
does not define progression.
The measurements of the 
new lesion(s) are included in 
the sum of the measurements.
Confirmation 
of PD
Not required
PD, in the absence of clinically significant 
deterioration, requires confirmation with repeat 
imaging after 4 to 6 weeks.
After initial PD following RECIST v1.1, shift to 
“RECIST 1.1 with confirmatory scan for PD”.
Required
Abbreviations:  irRC = immune-related response criteria; irRECIST = immune-related Response Evaluation Criteria 
in Solid Tumors; PD = progressive disease; RECIST = Response Evaluation Criteria in Solid Tumors.
9.1.1.2.
Application of RECIST 1.1 with Confirmatory Scan for Disease 
Progression
For Study JZEA, based on the unique response to immunotherapy and guidelines from regulatory 
agencies (for example, the EMA guideline on the evaluation of anticancer medicinal products in 
man for immune-modulating anticancer compounds [EMA 2013]), the following will be applied, 
in addition to standard RECIST 1.1 criteria:

If radiologic imaging verifies initial PD, tumor assessment should be repeated 4 to 
6 weeks later in order to confirm PD in the absence of clinically significant deterioration.  
Study treatment will continue between the initial assessment of progression and 
confirmation for progression.
“Clinically significant deterioration” is considered to be rapid tumor progression that necessitates 
treatment with anticancer therapy other than study treatment, or symptomatic progression that 
requires urgent medical intervention (for example, central nervous system metastasis, respiratory 
failure due to tumor compression, or spinal cord compression).

In the case of clinically significant deterioration, the patient will be discontinued from 
study treatment (Section 8.1).

Patients who continue to receive clinical benefit and who do not have clinically 
significant deterioration despite evidence of objective PD by the confirmatory scan may 
continue study treatment at the discretion of the investigator, in consultation with the 
Lilly CRP/CRS.
In determining whether or not progression can be confirmed, the site study team should consider 
all target lesions, nontarget lesions, and new lesions, and assess according to RECIST 1.1.


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9.1.1.3.
Criteria Required to Receive Treatment during Confirmatory Scan Period
In order for patients to continue receiving LY3415244, the following criteria apply:

absence of clinically significant deterioration (defined in Section 9.1.1.2) 

absence of clinical symptoms indicating clinically significant disease 
progression

no decline in performance status

no significant, unacceptable or irreversible toxicities related to study treatment

patient must sign the addendum consent prior to being treated during this time 
period
9.2.
Adverse Events
The investigator will use Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0 (NCI 2017) to assign severity grades.
Investigators are responsible for:

monitoring the safety of patients who have entered into this study and for 
alerting Lilly or its designee to any event that seems unusual, even if this 
event may be considered an unanticipated benefit to the patient.  

providing appropriate medical care of the patient during the study.

documenting their review of each laboratory safety report.

following, through an appropriate health care option, AEs that are serious or 
otherwise medically important, considered related to study treatment or the 
study, or that caused the patient to discontinue study treatment before 
completing the study.  The patient should be followed until the event resolves, 
stabilizes with appropriate diagnostic evaluation, or is reasonably explained.  
Frequency of follow-up evaluation is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish safety and toxicity.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  Study site personnel will record via eCRF any change in 
preexisting conditions and any new conditions as AEs.  Investigators should record their 
assessment of the potential relatedness of each AE to study treatment or study procedure via 
eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment or a study procedure, taking into account the disease, 
concomitant treatment or pathologies.  A “reasonable possibility” means that there is a cause and 
effect relationship between the study treatment and/or study procedure and the AE.


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Adverse Event grading of toxicities related to estimated Glomerular Filtration Rate (GFR) should 
be evaluated based on the Cockcroft-Gault method (Cockcroft and Gault 1976) or measured 
GFR.
Planned surgeries should not be reported as AEs unless the underlying medical condition has 
worsened during the course of the study.
Study site personnel must report any dose modifications or treatment discontinuation that results 
from AEs to Lilly or its designee via eCRF, clarifying, if possible, the circumstances leading to 
dose modification or discontinuation of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE during this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization 

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

important medical events that may not be immediately life-threatening or result in 
death or require hospitalization, may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient and may require 
intervention to prevent one of the other outcomes listed in the definition above.
Although all AEs after signing the ICF are recorded in the eCRF, SAE reporting to Lilly begins 
after the patient has signed the ICF and has received study treatment.  However, if an SAE 
occurs after signing the ICF, but prior to receiving study treatment, it needs to be reported ONLY 
if it is considered reasonably possibly related to study procedure.
Where permitted, study site personnel must notify Lilly or its designee of any SAE within 
24 hours of investigator awareness of the event via a Lilly-approved method.  If alerts are issued 
via telephone, they are to be immediately followed with official notification on study-specific 
SAE forms.  This 24-hour notification requirement refers to the initial SAE information and all 
follow-up SAE information.
Pregnancy (during maternal or paternal exposure to study treatment) does not meet the definition 
of an AE but should be reported.  To fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.
Investigators are not obligated to actively seek AEs or SAEs in patients once they have 
discontinued and/or completed the study (the patient disposition eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a patient has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.


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Planned hospitalizations or procedures for preexisting conditions that were recorded in the 
patient’s medical history at the time of study enrollment should not be considered SAEs.  
Hospitalization or prolongation of hospitalization without a precipitating clinical AE (for 
example, for the administration of study treatment or other protocol-required procedure) should 
not be considered SAEs.
Serious adverse events, including death, caused by disease progression should not be reported 
unless the investigator deems them to be possibly related to study treatment.
9.2.2.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to study treatment or study procedure.  The 
United States 21 CFR 312.32, the Regulation (EU) No 536/2014 and the associated detailed 
guidances or national regulatory requirements in participating countries require the reporting of 
SUSARs.  Lilly has procedures that will be followed for the recording and expedited reporting of 
SUSARs that are consistent with global regulatory regulations and the associated detailed 
guidances.
Regular communication will occur between investigators and the Lilly CRP/CRS via various 
channels (that is, email, regularly scheduled teleconference, Safety Reporting Notification 
System, etc.) to ensure that all parties are aware of how patients are tolerating LY3434172.  If in 
the event that sites need to be made aware of an emerging safety issue in a timely manner, Lilly 
will, upon confirmation of the event, communicate to site staff via email and/or direct telephone 
calls to ensure receipt of all of the information.  Lilly will follow-up with individual sites until 
receipt of the information is confirmed and that the site has taken the appropriate safety 
measures.  
9.2.3.
Complaint Handling
Lilly collects complaints on study drugs and drug delivery systems used in clinical studies in 
order to ensure the safety of study participants, monitor quality, and facilitate process and 
product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
Refer to the IB for intervention or comparator for available information on the signs, symptoms, 
and treatment of overdose.
9.4.
Safety
9.4.1.
Safety Measures
Refer to the Schedules of Activities (Section 2) regarding the timing of vital signs, laboratory 
tests, and other tests. 


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9.4.1.1.
Electrocardiograms
Perform ECGs as shown in Appendix 4.  Triplicate ECGs will be collected in Study JZEA at 
indicated time points in Appendix 4. During posttreatment follow-up period, single ECGs are 
collected. ECGs should be recorded according to the study-specific recommendations included 
in the ECG manual. 
ECG recording and vital sign measurements should occur prior to any blood draws scheduled at 
the same time point. Participants must be supine for approximately 5 to 10 minutes before ECG 
collection and remain supine but awake during ECG collection.
ECGs will be initially interpreted by a qualified physician at the site (the investigator or qualified 
designee) as soon after the time of ECG collection as possible (ideally while the patient is still 
present) to determine whether the patient meets entry criteria and for immediate patient 
management.
If a clinically significant quantitative or qualitative change from baseline is identified after 
enrollment, the investigator will assess the patient for symptoms (for example, palpitations, near-
syncope, or syncope) and to determine if the patient can continue in the study.  The investigator 
or qualified designee is responsible for determining if any change in patient management is 
needed and must document his/her review of the ECG printed at the time of evaluation.
Any clinically significant findings that result in a diagnosis and that occur after the patient
receives the first dose of study treatment should be reported to Lilly or its designee as an AE via 
eCRF.
All digital ECGs will be electronically transmitted to a designated central ECG laboratory.  The 
central ECG laboratory will perform a basic quality control check (for example, demographics 
and study details) and store the ECGs in a database. At a future time, the stored ECG data may 
be overread at the central ECG laboratory for further evaluation of machine-read measurements 
or to meet regulatory requirements.
The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes unless a central ECG laboratory cardiologist overread of the ECGs is conducted prior to 
completion of the final study report (in which case the overread data would be used).
For each set of replicates, the cardiologist will determine the R-R and QT intervals and heart rate 
on the ECGs.  These data are not routinely reported back to the investigative site.  However, any 
clinically significant finding that was not present on the fully overread ECG will be reported to 
the investigator and to Lilly.  All data from the overreads will be placed in the Lilly database for 
analytical and study report purposes.
The investigator’s (or qualified designee’s) ECG interpretation will be used for decisions about 
study entry and immediate patient management will be based on the investigator's or qualified 
designee's ECG interpretation.  Data analysis will be based on ECG interpretations performed by 
the cardiologist at the central ECG laboratory.


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9.4.2.
Safety Monitoring
Lilly will review safety data on a cohort by cohort basis and periodically review evolving 
aggregate safety data within the study by appropriate methods. 
Lilly has systematic and robust internal processes in place that ensure safety surveillance of 
development compounds in line with the US Food and Drug Administration (FDA)’s 
expectations for safety assessment committees (SACs) (FDA Draft Guidance: “Expansion 
Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and 
Biologics”; FDA Draft Guidance: “Master Protocols: Efficient Clinical Trial Design Strategies to 
Expedite Development of Oncology Drugs and Biologics”; FDA Draft Guidance: “Safety 
Assessment for IND Safety Reporting”; FDA Guidance: “Safety Reporting Requirements for 
INDs and BA/BE Studies”). This includes processes with clearly described roles and 
responsibilities that are owned by Lilly’s Global Patient Safety organization.  These processes 
are designed to monitor the evolving safety profile (i.e., review of cumulative SAEs, other 
important safety information) by designated cross-functional teams in a timely manner at pre-
defined intervals or on an ad-hoc basis. In addition, a dedicated process may be used to perform 
unblinded comparisons of event rates for SAEs as necessary.  
This system ensures that the accumulating safety data derived from individual and multiple trials 
across a development program is reviewed on a regular basis and that important new safety 
information, such as the need for protocol modification or other relevant safety related material, 
is identified and communicated to regulators and investigators appropriately and in a timely 
fashion.  An internal review of aggregate safety data occurs on at least a quarterly basis or more 
frequently, as appropriate.  Any serious adverse reactions are reported within the required 
timeline for expedited reporting.
In addition to annual periodic safety updates and to further inform investigators, a line listing 
report of SUSARs is created and distributed to investigators on a biannual (twice yearly) basis. 
Any significant potential risk/safety concerns that are being monitored as well as any results 
being reported in other periodic reports for the compound; SAC decisions; and other significant 
safety data (for example, nonclinical or clinical findings, removal of serious adverse reactions) 
are included in the report.
If a study patient experiences elevated alanine aminotransferase (ALT) >5X upper limit of 
normal (ULN) and elevated total bilirubin (TBL) >2X ULN, or ALT ≥8X ULN, liver tests
(Appendix 6) should be repeated within 3 to 5 days including ALT, AST, TBL, direct bilirubin
(D.TBL), gamma-glutamyl transferase (GGT), and creatine phosphokinase (CPK) to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator based on the 
hepatic monitoring tests (Appendix 6) and in consultation with the Lilly CRP/CRS. Monitoring 
of ALT, AST, and TBL should continue until levels normalize or return to approximate baseline 
levels.


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9.4.2.1.
Guidance for Monitoring Vasculitis
In the preclinical toxicology studies with LY3434172, vascular/perivascular mononuclear or 
mixed cell infiltrates were observed in both large and small vessels, whereby various organs 
were affected. While this is not an uncommon finding with human antibodies in non-human 
primates, it is unknown if vasculitis poses a potential risk in humans. 
Given the nature of the findings in animals and heterogeneity associated with vasculitis, patients
should be monitored for clinical signs and systemic laboratory tests described below for possible 
signs of vasculitis. There are some overlapping clinical features and laboratory tests to those 
observed for irAE and management of these AEs should be in accordance with local guidelines 
(Brahmer et al. 2012, Hannen et al. 2017, Puzanov et al. 2017) or Table JZEA.11.  A 
rheumatologist (preferably with specialist knowledge in diagnosis and treatment of vasculitis) 
should be consulted if vasculitis is suspected.
Clinical signs of potential vasculitis:

Skin: palpable purpura, skin ulcers. In the case of cutaneous vasculitis, 2 skin punch 
biopsies (deep dermis should be captured as part of the biopsy) of the affected area 
should be obtained. One core could be collected in formalin and processed for H&E 
assessment and the second core biopsy flash frozen.

Mucous membranes: new onset oral ulcers that do not resolve within a week

Ophthalmologic symptoms: blurred vision, vision loss, periorbital swelling

Ear, nose or throat: New onset bloody nasal discharge/crust/ulcers that does not resolve 
within a week, sinusitis, sudden onset of hearing loss

Lungs/respiratory: Hemoptysis, respiratory failure, infiltrates, appearance of nodules on 
imaging (thoracic CT scan) not attributable to other causes (e.g., immune related 
pneumonitis)

Gastrointestinal: Bloody diarrhea, ischemic abdominal pain

Renal and urinary: Hypertension, proteinuria, hematuria ≥10 RBCs/hpf, RBC casts, 
elevated serum creatinine

Nervous system: New onset loss of motor function
Systemic laboratory test:

Complete blood count (CBC), liver enzymes, creatinine, urinalysis with microscopy 
should be evaluated together with clinical features listed above for hematologic, renal or 
other organ involvement.

Erythrocyte sedimentation rate (ESR) elevation suggestive of inflammation if not already 
elevated due to underlying malignancy.

C-reactive protein elevation suggestive of inflammation if not already elevated due to 
underlying malignancy.

C3a complement will be tested as indicated in table (Table JZEA.1 and Table JZEA.2).

C-ANCA and P-ANCA values will be captured at baseline and as indicated
o
if positive, additional tests for myoperoxidase (MPO) and proteinase-3 (PR3) 
antibodies are required.


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9.4.2.2.
Special Hepatic Safety Data Collection
Hepatic data should be collected (see Appendix 6) in the event that a patient meets one of the 
following conditions during the course of the study: 

elevation of serum ALT to ≥10X ULN

patients without liver tumors or liver metastasis: ALT≥5X ULN and TBL≥ 2X 
ULN

patients with liver tumors or liver metastasis: ALT≥8X ULN and TBL≥ 2X ULN

discontinuation from treatment due to a hepatic event or abnormality of liver tests

occurrence of a hepatic event considered to be a SAE
9.5.
Pharmacokinetics
Pharmacokinetic samples will be collected as shown in Appendix 4.
Blood samples will be used to determine the study drug concentrations of LY3434172 (also 
known as bioanalytical samples).  
Instructions for the collection and handling of bioanalytical blood samples will be provided by 
Lilly.  The actual start and end date and time of LY3434172 infusion must be recorded on the 
eCRF.  The actual date and time that each bioanalytical blood sample is drawn must be recorded 
on the laboratory requisition page after the sample is drawn.
All study drug concentrations in bioanalytical serum samples will be measured using a validated 
enzyme-linked immunosorbent assay in a laboratory designated by Lilly.
Bioanalytical samples collected to measure study drug concentrations will be retained for a 
maximum of 1 year following last subject visit for the study. During this time, samples 
remaining after the bioanalyses may be used for exploratory metabolism studies or exploratory 
analyses such as bioanalytical assay validation or cross-validation exercises.
9.6.
Pharmacodynamics
Pharmacodynamic samples will be collected as shown in Appendix 4 to assess target 
engagement and activity for LY3434172.  Potential pharmacodynamic markers may include 
measuring soluble markers (sPD-L1 and sPD-1) in serum, cytokine levels (i.e. IL-2 and IFNy) in 
blood samples after ex vivo stimulation with staphylococcal  enterotoxin B (SEB) and anti-CD28 
agonist, and immune cell subsets characterization and distribution.  Tumor tissue, plasma, serum, 
and whole blood may be used for additional exploratory pharmacodynamics testing as deemed 
appropriate by Lilly (see also Section 9.8). Samples collected to measure pharmacodynamic 
biomarkers will be identified by the patient number (coded) and retained at a facility selected by 
the Lilly for a maximum of 15 years following last patient visit for the study.
9.6.1. Immunogenicity Assessments 
Blood samples for IG testing will be collected as shown in Appendix 4 to determine antibody 
production against LY3434172.  Immunogenicity will be assessed by a validated assay designed 


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 6 4
L Y 3 4 3 4 1 7 2
t o detect A D As i n t he prese nce of L Y 3 4 3 4 1 7 2 .  A nti b o dies ma y be f urt her c haracterize d a n d/ or 
e val uate d f or t heir a bilit y t o ne utralize t he acti vity of  L Y 3 4 3 4 1 7 2 . 
I n t he e ve nt of a n I R R, bl o o d sa m ples will be c ollecte d f or P K, A D A a n d e x pl orat or y i m m u ne 
safety a nal yses at t he f oll o wi n g t i me p oi nts, as close as p ossi ble t o: (i ) t he o nset of t he I R R,
(ii) t he res olut i on of t he I R R, a n d (iii) 3 0 [ ± 3] da y s fol l owi n g t he I R R. 
 
 
I nstr ucti o ns f or t he c ollecti on a n d 
ha n dli n g of bl o o d sa m ples will be pr o vi de d b y  t he Lill y C R P/ C R S . T he act ual date a n d ti me 
( 2 4-h o ur cl oc k ti me) of eac h sa m pli n g will be rec or de d . 
S a m ples will  be retai ne d at a facilit y selecte d b y  Lill y for a m a xi m u m of 1 5 years after last t he 
pati e nt visit for t he st u d y , or for a s h orter peri o d if re g ul at i ons a n d et hical re vie w b oar ds 
( E R Bs)/i nstituti o nal  re vie w b oar ds (I R Bs) i m p ose s h orter ti me limit s.  T he d urati o n all o ws Lill y 
t o res p o n d t o f ut ure re g ulat or y re q uests relate d t o L Y 3 4 3 4 1 7 2 . A n y sa m ples re mai ni n g after 1 5 
years will be destr o y e d.
9. 7.
G e n eti c s
9. 7. 1.
W h ol e Bl o o d S a m pl e f or P h ar m a c o g e n eti c R e s e ar c h
A w h o le bl o o d sa m ple will be c ollecte d f or p har mac o ge net ic a nal ysis as s pecifie d i n A p pe n di x 
4 , w here lo c al  r e g ulat i ons all o w.
S a m ples will  not be use d t o c o n d uct u ns pecifie d disease or p o p ulat i on ge net ic researc h eit her 
n o w or i n t he f ut ure.  Sa m ples will be use d t o i n vesti gate varia ble res p o nse t o L Y 3 4 3 4 1 7 2 a n d t o 
i n vesti gate ge netic varia nts t h o u g h t t o pla y a r ole i n ca ncer.  Assess me nt of varia ble res p o nse 
ma y i ncl u de e val u ati o n of  A Es or differe nces i n efficac y.
All sa m ples will be c o de d wit h t he patie nt n u m ber.  T hese sa m ples a n d a n y data ge nerate d ca n 
be li n ke d bac k t o t he patie nt o nl y b y t he st u d y site pers o n nel.  Sa mples will  be retai ne d at a 
facility selected b y  Lill y f or a ma xi m u m of 1 5 year s after t he last patie nt visit f or t he st u d y, or 
f or a s h orter perio d if l ocal re g ulati o ns a n d/ or E R Bs/I R Bs i m p ose s h orter ti me li mits.  T his 
rete ntio n peri o d e na bles use o f ne w tec h n o l ogi es, res p o nse t o q uesti o ns fr o m reg ul at or y 
a ge ncies, a n d i n vest i gati on of varia ble res p o nse t hat ma y n ot be o bser ve d u nt il later i n t he 
de vel o p me nt of L Y 3 4 3 4 1 7 2 or after L Y 3 4 3 4 1 7 2 bec o mes c o m merciall y a vaila ble.
M olec ular tec h n o l ogi es are e x pecte d t o i m pr o ve d uri n g t he 1 5 year st ora ge peri o d a n d t heref ore 
ca n n ot be s pecificall y na me d.  H o we ver, e xisti n g tec h n ol ogi es i ncl u de w h ole ge n o me a n d e x o me 
se q ue nci n g, ge n ome -wi de ass oci at i on st u dies, m ulti ple x assa ys, a n d ca n di date ge ne st u dies.  
Re gar dless of t he tec h n o l og y  utilize d, data ge nerate d will be use d o nl y f or t he s pecific researc h 
sc o pe descri be d i n t his secti on.
C CI


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9.8.
Biomarkers 
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics, mechanism of action, variability of patient response (including 
safety), and clinical outcome.  Sample collection is incorporated into clinical studies to enable 
examination of these questions through measurement of biomolecules including DNA, RNA, 
proteins, lipids, and other cellular elements.  
As part of Lilly’s ongoing efforts to understand the relationship between cancer, genetics, and 
response to therapy, this study will analyze systemic and tumor tissue-associated biomarkers 
relevant to LY3434172, mechanism of action of LY3434172, the variable response to study 
drug(s), immune function, and pathways associated with cancer.  These samples may also be 
used to develop related research methods or to validate diagnostic tools or assays.
Samples for biomarker research will be collected as specified in Appendix 4, where local 
regulations allow.  It is possible that biomarker data for patients in the study has already been 
generated from samples that were collected and analyzed prior to enrolling in this study.  This 
may include data generated from genetic analyses.  If available, these data may be requested 
from medical records for use in the research described in Sections 9.7.1, 9.8.1, and 9.8.2. 
9.8.1.
Tissue Samples for Biomarker Research
Tissue samples for biomarker research will be collected for the purposes described in 
Section 9.8.  The following samples for biomarker research will be collected as specified in
Appendix 4, where local regulations allow.
Collection of the following tumor tissue sample(s) is required for all patients in order to 
participate in this study.
For patients participating in all cohorts:

a newly obtained core or excisional pre-treatment biopsy of a tumor lesion from
metastatic site and

a tumor tissue sample from a newly obtained core or excisional biopsy specimen 
collected during the study treatment period as shown in Appendix 4.  

an archival formalin-fixed paraffin-embedded tumor tissue obtained from the primary 
tumor site, if available and not restricted by local regulations. (Regardless of whether or 
not the archival tissue is submitted, patients are still required to undergo pretreatment and 
on-treatment biopsies).
An attempt to obtain up to 4 core-needle biopsies or a surgical biopsy is required, unless 
medically contraindicated or unsafe and discussed with Lilly CRP/CRS. Optimally, biopsies 
should be taken from the same metastatic lesion and from areas not previously irradiated (except 
if the patient had progressed after radiation).  For tumor tissue samples that are not archived, the 
subject has to be willing to undergo baseline and on-study biopsies that should not put subjects at 
undue risk greater than that which comes with a core biopsy, in other words, a procedure to 
obtain biopsy should have a serious/severe complication risk no greater than 2%.


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If a biopsy does not contain adequate tissue for analysis, the patient may be replaced.  Lilly may
replace up to 25% patients, if unable to submit an adequate tumor sample.
Collection of the following tumor tissue sample(s) is optional for all patients participating in this 
study:
For patients participating in all cohorts

a tumor tissue sample from a newly obtained biopsy specimen collected after disease 
progression or at additional study time points, if warranted and agreed upon by the 
investigator and Lilly. Such additional biopsies are optional and should be performed 
only if clinically feasible. If these additional samples are requested, they will be used to 
further investigate biomarkers that may explain treatment response and resistance 
mechanisms.  If a biopsy is performed after the patient signs the ICF, Lilly may request a 
tissue sample from the biopsy for additional biomarker testing at any time during the 
study including post-progression.
Newly acquired tumor biopsies are requested because they provide the most current biomarker 
characteristics of the tumor compared with biopsies taken at the time of diagnosis (tumor 
characteristics may shift during subsequent lines of treatment).  Pre- and on-treatment 
assessments are critical to evaluate changes in molecular markers over time and to document any 
potential immunomodulatory activity of treatment with LY3434172 and should be performed if 
clinically feasible. Samples will be examined for biomarkers as described in Section 9.8, 
including but not limited to, PD-L1 expression by immunohistochemistry.
The tissue samples should be obtained using an appropriate method.  Tumor tissue should be 
submitted as a newly acquired excisional or core needle (minimum 18 gauge) or surgical biopsy 
in formalin. Cytological or fine-needle aspiration, bone specimens are not acceptable. If 
additional tumor biopsies are collected as part of clinical care, they should be submitted, along
with pathology reports, for further analysis. See the Laboratory Manual for details regarding 
sample handling.  At the time of tissue collection process, due diligence should be used to make 
sure that the tumor sample (not a normal adjacent tissue sample or a tumor margin sample) is 
provided and contains tumor cells prior to shipment to the central laboratory.  This will help 
ensure that a quality biopsy sample has been taken. 
The pathology report accompanying archival tissue may also be requested.  The pathology report 
must be coded with the patient number.  Personal identifiers, including the patient’s name and 
initials, must be removed from the institutional pathology report prior to submission.  Lilly has a 
right to retain a portion of the submitted tissue, Archival blocks will be sectioned and returned to 
the study site.  Slides and tissue samples collected on-study will not be returned.
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and/or ERBs/IRBs impose 
shorter time limits.  This retention period enables the use of new technologies, response to 
questions from regulatory agencies, and investigation of variable response that may not be 


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observed until later in the development of LY3434172 or after LY3434172 becomes 
commercially available.
Technologies are expected to improve during the 15-year storage period and therefore cannot be 
specifically named.  Existing approaches, including but not limited to mutation profiling, copy 
number variability analysis, gene expression assays, multiplex assays, and/or 
immunohistochemistry may be performed on these tissue samples to assess potential associations 
between these biomarkers and clinical outcomes.
9.8.2.
Other Samples for Biomarker Research 
The following samples for biomarker research will be collected for the purposes described in 
Section 9.8, and as specified in Appendix 4, where local regulations allow. 

Whole blood 

Serum

Plasma

Stool (when applicable, stool specimens may be collected for microbiome 
analyses)

A maximum of 5 samples may be collected at additional time points during the 
study, if warranted and agreed upon by the investigator and Lilly. If these 
additional samples are requested, they will be used to further investigate 
biomarkers that may explain treatment response and resistance mechanisms.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the study site personnel.  
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and/or ERBs/IRBs impose 
shorter time limits.  This retention period enables use of new technologies, response to questions 
from regulatory agencies, and investigation of variable response that may not be observed until 
later in the development of LY3434172 or after LY3434172 becomes commercially available.
Technologies are expected to improve during the 15-year storage period and therefore cannot be 
specifically named.  Existing approaches, including but not limited to flow cytometry, mutation 
profiling, copy number variability analysis, gene expression assays, multiplex assays may be 
performed on these samples to assess potential associations between these biomarkers and 
clinical outcomes.
9.9.
Health Economics
Health economics and medical resource utilization parameters will not be evaluated in this study.


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10.
Statistical Considerations
10.1. Sample Size Determination
The primary objective of this study is to assess the safety and tolerability of LY3434172, thereby 
identifying and confirming the RP2D of LY3434172 to be administered as monotherapy to 
patients with solid tumors.  The secondary objective is to evaluate PK and any observed evidence 
of clinical efficacy.  
The total sample size in Cohorts A1 to A5/A6 will be determined by the incidence of DLTs.  The 
RP2D could be chosen after the corresponding Q2W cohorts have been enrolled. After the DLT 
period (Cohorts A1 to A5/A6) is completed, an additional 12 to 15 patients at two dose levels
selected from these cohorts will be enrolled for adequate assessment of safety and exploration of 
PK and pharmacodynamic effects. In parallel, patients will be enrolled in Q3W cohorts (A7 and 
A8) to allow flexibility for future combinations with standard-of-care agents. The sample size of 
Q3W depends primarily on PK profiles and clinical considerations.
10.2. Populations for Analyses
The following analysis sets will be defined for this study.
Enrolled/Safety population:  will include all patients who received any quantity of study 
treatment, regardless of their eligibility for the study.  The safety and efficacy evaluation will be 
performed based on the first dose of study treatment a patient actually received. This population 
will be used for all dosing/exposure, safety, and efficacy analyses.
Pharmacokinetic analysis set:  will include all enrolled patients who received at least one dose 
of LY3434172 and have at least one evaluable PK sample.
Biomarker analysis set:  will include the subset of enrolled patients from whom a valid assay 
result has been obtained. No imputation will be performed for missing data due to the limitation 
of small sample size.
10.3. Statistical Analyses
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Unless otherwise stated, all confidence interval (CIs) will be given at a 2-sided 95% level.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the Statistical Analysis Plan (SAP) and clinical study report (CSR).  Additional exploratory 
analyses of the data will be conducted as deemed appropriate.
10.3.1. Safety Analyses
All patients who receive any quantity of LY3434172 will be evaluated for safety and toxicity.  
Severity grades will be assigned by the investigator using CTCAE Version 5.0.


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Safety analyses will include summaries of the following:

DLTs:  the number of patients who experience any DLTs during Cycle 1 will be 
summarized by cohort by treatment arm

DLT-equivalent:  the number of patients who experience any AE that qualifies as a DLT 
during any period of study will be summarized by the first dose by treatment arm and by 
tumor type

AEs, including severity and possible relationship to study drug

AEs by Medical Dictionary for Regulatory Activities system organ class (SOC) by 
decreasing frequency of Preferred Term within an SOC

laboratory and non-laboratory AEs by CTCAE Version 5.0 term, maximum CTCAE 
grade, and CTCAE Grade 3 and above (regardless of causality and at least possibly 
related to study treatment)

changes in vital signs and ECGs
10.3.2. Efficacy Analyses
The study was not designed to make an efficacy assessment. However, any tumor response data 
will be tabulated, where appropriate, for all patients in the enrolled/safety analysis set.  
The efficacy endpoints are listed and defined as follows:
Objective response rate (ORR) is the proportion of enrolled patients who have received any 
amount of either study drug, have at least one postbaseline tumor image, and achieved a best 
overall response (BOR) of confirmed CR or PR.
Duration of response (DoR) is defined only for responders (patients with a confirmed CR or 
PR).  It is measured from the date of first evidence of a confirmed CR or PR to the date of the 
first observed radiographically documented PD, or the date of death due to any cause, whichever 
is earlier.  If a responder is not known to have died or have objective progression as of the data 
inclusion cutoff date, DoR will be censored at the date of the last complete objective 
progression-free disease assessment.
Time-to-response (TTR) is the time from the date of first study treatment until the first 
evidence of a confirmed CR or PR.
Disease control rate (DCR) is the proportion of enrolled patients who have a BOR of confirmed 
CR, confirmed PR, or stable disease (SD).
Progression-free survival is defined as the time from the date of first study treatment until the 
date of the first observed radiographically documented PD or death due to any cause, whichever 
is earlier.  The censoring is taken in the following order:

If a patient does not have a complete baseline disease assessment, then the PFS time will 
be censored at the enrollment date, regardless of whether or not objectively determined 
disease progression or death has been observed for the patient; otherwise,


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
if a patient is not known to have died or have objective progression as of the data 
inclusion cutoff date for the analysis, the PFS time will be censored at the last complete 
objective progression-free disease assessment date.
Overall survival, an exploratory objective, is determined from the date of first study treatment 
until death due to any cause.  If the patient is not known to have died at the data inclusion cutoff 
date for the analysis (or is lost to follow-up), OS will be censored on the last date the patient was 
known to be alive.  This endpoint will be followed up for 12 months after the last patient has 
entered treatment.
The objective response rate, TTR, DCR, DoR, and PFS will be assessed based on RECIST v1.1 
(Eisenhauer et al. 2009) and RECIST v1.1 with confirmatory scan for disease progression 
(Section 9.1.1).
The estimate of ORR and DCR, and the corresponding CI, will be provided by dose-level 
(cohort) according to RECIST v1.1 and RECIST v1.1 with confirmatory scan for disease 
progression (Section 9.1.1).  Time-to-event variables, such as TTR, DoR, PFS (as an exploratory 
objective), and OS (as an exploratory objective), will be summarized by Kaplan and Meier 
(1958) method by dose-level (cohort) where appropriate.  Presentations of antitumor activity 
may include patients enrolled in the dose-level (cohort) with the same tumor type and dosing 
scheme.  Individual changes in the tumor burden over time will be presented graphically within a 
tumor type.  Subgroup analysis of interest will be further defined in the SAP.
10.3.3. Other Analyses
10.3.3.1. Patient Disposition
A detailed description of patient disposition will be provided, including a summary of the 
number and percentage of patients entered into the study, enrolled in the study, and treated as 
well as number and percentage of patients completing the study, as defined in the SAP, or 
discontinuing (overall and by reason for discontinuation).  A summary of all important protocol 
deviations will be provided.
10.3.3.2. Patient Characteristics
Demographic data are collected and reported using descriptive statistics.
A summary of baseline patient and disease characteristics, historical diagnoses, preexisting 
conditions, and prior therapies will be reported using descriptive statistics. 
Other patient characteristics at baseline will be summarized as deemed appropriate.
10.3.3.3. Concomitant Therapy
A summary of prior and concomitant medications will be reported.
10.3.3.4. Treatment Compliance
The number of cycles received, dose omissions, dose reductions (if any), dose delays, and dose 
intensity will be summarized for all treated patients by treatment arm.


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LY3434172 will be administered at the investigator site, therefore treatment compliance is 
assured.
10.3.3.5. Pharmacokinetic/Pharmacodynamic Analyses
Selected PK descriptors (based on actual sampling times), including approximate Cmax and AUC 
will be calculated by noncompartmental analysis methods. As an exploratory analysis, PK 
descriptor estimates for trough concentrations (Cmin) at steady state following repeated dose may 
be evaluated.
In addition, PK parameter estimates for LY3434172 may be calculated by population PK 
analysis methods using nonlinear  mixed effects modeling (NONMEM). The version of any 
software used for the analysis will be documented, and the program will meet the Lilly 
requirements of software validation. It is possible that other validated, equivalent PK software 
programs may be used if appropriate, warranted, and approved by Global PK/pharmacodynamic 
management.
Following review of the biomarker analyses (see Section 10.3.3.6), pharmacodynamics 
biomarker analysis with tumor type, changes in biomarker levels over time, and association to 
dose levels or exposure might be explored if applicable. Pharmacokinetics/Pharmacodynamics
analyses may be conducted to explore exposure-response relationships between LY3434172 
concentrations in systemic circulation and relevant pharmacodynamics measures such as soluble 
PD-1, soluble PD-L1 and IL-2 stimulation. Either summary metrics of exposure and effect (for 
example, individual trough concentrations) or concentration time profiles of exposure and effect 
could be used for these analyses.
10.3.3.6. Biomarker Analyses
The relationship between biomarkers and clinical outcome may be assessed. If the ORR is 
greater than or equal to 10%, the baseline biomarkers that potentially predict better response to 
LY3434172 may be explored using single- or multi-marker approach. Association analysis from 
selected biomarkers to the clinical endpoints will be explored if applicable. 
10.3.3.7. Immunogenicity Analyses
The frequency and percentage of patients with preexisting ADA, ADA at any time point 
postbaseline, and with treatment-emergent ADA positivity (TE ADA+) to LY3434172 will be 
tabulated.  Treatment-emergent ADAs are defined as those with a titer 2-fold (1 dilution) greater 
than the minimum required dilution if no ADAs were detected at baseline (treatment-induced 
ADA) or those with a 4-fold (2 dilutions) increase in titer compared to baseline if ADAs were 
detected at baseline (treatment-boosted ADA).  For the TE ADA+ patients, the distribution of 
maximum titers will be described.  The frequency of neutralizing antibodies may also be 
tabulated in TE ADA+ patients.
The relationship between the presence of antibodies and the PK parameters and 
pharmacodynamic response including safety and efficacy to LY3434172 may be assessed.


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10.3.4. Interim Analyses
Safety, PK, and biomarker data (if available) will be reviewed on a cohort-by-cohort basis during 
the study, until the MTD and/or RP2D is determined.  The purpose of these cohort-by-cohort 
data reviews is to evaluate the safety data at each dose level and determine if a DLT has been 
observed.  The decision whether to advance to the next dose level will be made following 
discussion between the investigators and Lilly and will be relayed to the sites prior to patients 
being treated on the subsequent cohort. 
Safety and available PK data will be reviewed during the study to inform dose escalation, 
modifications to the dose-escalation strategy, or other design elements.
An interim analyses will be performed after all patients from cohorts A1 to A5/6 have completed 
the DLT evaluation period. Additional enrolment of 12-15 patients from these cohorts at two 
dose levels (yet to be determined) can continue during IA.
Interim analyses may also be combined with any prespecified safety review or reporting
(i.e. Trial Level Safety Reviews, Development Safety Update Reviews, or IB update reviews).  
The final overall analysis of Study JZEA will coincide with the safety and efficacy primary 
analysis of the last cohort.
If it is deemed that enough data have been obtained to assess the primary and secondary 
objectives, a CSR might be created before the last patient visit.  In this case, all data until the 
data-cutoff date will be used for the analysis of safety, efficacy, PK, and pharmacodynamic
biomarkers.  All data defined in the protocol will continue to be collected from patients on 
treatment after data-cutoff date and results may be listed.  However, summary tables including 
data after data-cutoff date will not be created.


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11.
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Flowers CR, Seidnefled, J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston 
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monoclonal antibody-induced immune complex disease in cynomolgus monkeys (Macaca 
fascicularis). Toxicol Pathol. 2014;42(4):765-773.
Husar E, Solonets M, Kuhlmann O, Schick E, Piper-Lepoutre H, Singer T, Tyagi G.  
Hypersensitivity reactions to obinutuzumab in cynomolgus monkeys and relevance to humans.  
Toxicol Pathol. 2017;45(5):676-686.
Jenkins RW, Thummalapalli R, Carter J, Cañadas I, Barbie DA.  Molecular and Genomic 
Determinants of Response to Immune Checkpoint Inhibition in Cancer. Annu Rev Med. 2018 
;69:333-347.
Kaplan EL, Meier P. Nonparametric estimation of incomplete observations. J Amer Stat Assoc. 
1958;53(282):457-481.
Kronenberg S, Husar E, Schubert C, Freichel C, Emrich T, Lechmann M, Giusti AM, Regenass 
F.  Comparative assessment of immune complex-mediated hypersensitivity reactions with 
biotherapeutics in the non-human primate: critical parameters, safety and lessons for future 
studies.  Regul Toxicol Pharmacol. 2017;88:125-137.
Leach MW, Rottman JB, Hock MB, Finco D, Rojko JL, Beyer JC. 
Immunogenicity/hypersensitivity of biologics.  Toxicol Pathol. 2014;42(1):293-300.
[NCI] National Cancer Institute. Cancer Therapy Evaluation Program, Common Terminology 
Criteria for Adverse Events, Version 5.0, DCTD, NCI, NIH, DHHS. 2017. Published 27 
November 2017.
Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a 
common language for tumor response to immunotherapy: immune-related response criteria 
using unidimensional measurements. Clin Cancer Res. 2013;19(14):3936-43.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5:649-655.
Parchment RE, Voth AR, Doroshow JH, Berzofsky JA. Immuno-pharmacodynamics for 
evaluating mechanism of action and developing immunotherapy combinations. Semin Oncol. 
2016;43(4):501-513.
Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, Dadu R, Hamad L, Kim S, 
Lacouture ME, LeBoeuf NR, Lenihan D, Onofrei C, Shannon V, Sharma R, Silk AW, Skondra 
D, Suarez-Almazor ME, Wang Y2 Wiley K, Kaufman HL, Ernstoff MS; Society for 
Immunotherapy of Cancer Toxicity Management Working Group. Managing toxicities 
associated with immune checkpoint inhibitors: consensus recommendations from the Society 
for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother 
Cancer. 2017;5(1):95.
Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, 
Djulbegovic B, Goode MJ, Jakubowski AA, Rarick MU, Regan DH, Lichtin AE; American 
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12.
Appendices


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Appendix 1. Abbreviations and Definitions
Term
Definition
ADA
anti-drug antibody
AE
Adverse event:  any untoward medical occurrence in a patient or clinical 
investigation patient administered a pharmaceutical product and does not 
necessarily have a causal relationship with this treatment.  An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of 
medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
BED
biologically effective dose
BOR
best overall response
Cavg
2-week average concentration
Cmax
maximum plasma concentration
Cmin
trough concentration
CBC
complete blood count
cDNA
complementary DNA
CI
confidence interval
CL
clearance
CNS
central nervous system
collection database
A computer database where clinical study data are entered and validated.


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CR
complete response
CrCl
creatinine clearance 
CRP
clinical research physician: individual responsible for the medical conduct of the 
study.  Responsibilities of the CRP may be performed by a physician, clinical 
research scientist, global safety physician or other medical officer.
CRS
clinical research scientist
CSR
clinical study report
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
Ctrough
lowest concentration of drug just prior to the next dose
DCR
disease control rate:  the percentage of patients with a best response of CR, PR, or 
SD.
DLT
dose-limiting toxicity
DLT-ET
DLT-equivelant toxicity
DoR
duration of response: the time from the date measurement criteria for CR or PR 
(whichever is first recorded) are first met until the first date that disease is 
recurrent or objective progression is observed, per RECIST 1.1 criteria, or the 
date of death from any cause in the absence of objectively determined disease 
progression or recurrence.
ECG
electrocardiogram
eCRF
electronic case report form
EI
equivalence interval
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the 
study are those who have been assigned to a treatment and have received at least 
one dose of study treatment.
ERBs/IRBs
ethical review boards/institutional review boards
Enter
Patients entered in the study are those who have signed the informed consent 
form directly or through their legally acceptable representatives.
ESR
erythrocyte sedimentation rate
FDA
Food and Drug Administration
FIH
first in human
GCP
good clinical practice


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G-CSF
granulocyte colony stimulating factors
GFR
glomerular filtration rate
HCC
hepatocellular
highly effective method 
of contraception
Methods include
•
combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:
o
oral
o
intravaginal
o
transdermal
•
progestogen-only hormonal contraception associated with inhibition of 
ovulation:
o
oral
o
intravaginal
o
transdermal
•
intrauterine device 
•
intrauterine hormone-releasing system
•
bilateral tubal occlusion 
•
vasectomized partner (vasectomized partner is a highly effective birth 
control method provided that partner is the sole sexual partner of the woman of 
childbearing potential who is the trial participant and that the vasectomized 
partner has received medical assessment of the surgical success.)
•
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 treatments. The reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the clinical 
trial and the preferred and usual lifestyle of the subject.) 
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
irAEs
immune-related adverse events
IRR
infusion-related reaction
ICF
informed consent form
ICH
International Conference on Harmonization
IG
immunogenicity
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IgM
immunoglobulin M


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interim analysis
An analysis of clinical study data that is conducted before the final reporting 
database is authorized for datalock.
IRR
infision-related reaction
irRC
immune-related response criteria
Investigational product 
A pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study including products already on the market when used 
or assembled (formulated or packaged) in a way different from the authorized 
form, marketed products used for an unauthorized indication or marketed 
products used to gain further information about the authorized form.
IV
intravenous
IWRS
interactive web-response system
LPET
last patient enters/starts study treatment
mAb
monoclonal antibody
MABEL
minimum anticipated biological effect level
MPO
myoperoxidase
MTD
maximum tolerated dose
mTPI-2
modified toxicity probability interval-2
NK cells
natural killer cells
NOAEL
no-observed-adverse-effect-level
NONMEM
nonlinear  mixed effects modeling
NSCLC
non-small cell lung cancer
NSG
nod-SCID gamma
open-label
A study in which there are no restrictions on knowledge of treatment allocation, 
therefore the investigator and the study participants are aware of the drug therapy 
received during the study.
ORR
objective response rate: the percentage of patients who achieve a best overall 
response (BOR) of CR or PR 
OS
overall survival
PD
progressive disease 
PD-1
programmed death 1
PD-L1
programmed death ligand 1


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PFS
progression-free survival: the time from randomization until the first radiographic 
documentation of progression or death from any cause in the absence in 
progressive disease.  
PK
pharmacokinetic
PR
partial response
PR3
proteinase-3
RECIST
Response Evaluation Criteria in Solid Tumors
reporting database
A point-in-time copy of the collection database.  The final reporting database is 
used to produce the analyses and output reports for interim or final analyses of 
data.
Re-screen
to screen a patient who was previously declared a screen failure for the same 
study
RP2D
recommended Phase 2 dose
SAC
safety assessment committee
SAE
serious adverse event
SAP
Statistical Analysis Plan
screen
The act of determining if an individual meets minimum requirements to become 
part of a pool of potential candidates for participation in a clinical study.
Screen failure
A patient who does not meet one or more criteria required for participation in a 
study
SEC
staphylococcal  enterotoxin B
sPD-L1
soluble programmed death ligand 1
SOC
system organ class
SUSAR
suspected unexpected serious adverse reactions
TBL
total bilirubin
TE
target engagement
TEAE
Treatment-emergent adverse event:   an untoward medical occurrence that 
emerges during a defined treatment period, having been absent pretreatment, or 
worsens relative to the pretreatment state, and does not necessarily have to have a 
causal relationship with this treatment.
TMDD
Target Mediated Drug Disposition
TTR
Time-to-response


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Vd
volume of distribution
WOCBP
Women of childbearing potential; females who have attained menarche and are 
not menopausal or surgically sterile.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 8 3
L Y 3 4 3 4 1 7 2
A p p e n di x 2.
Cli ni c al L a b or at or y  T e st s
He m at ol o g y – l ocal la b orat or y

Le u k oc ytes ( W B C)

Ne utr o p hils a

L y m p h oc y t es

M o n oc ytes

E osi n o p hils

Bas o p hils

Er y t hr oc ytes ( R B C)

He m o gl o bi n ( H G B)

He mat ocrit ( H C T)

Platelets ( P L T)
C o a g ul ati o n – l ocal la b orat or y
Acti vate d partial t hr o m b o plasti n ti me (a P T T) or partial t hr o m b o plasti n ti me ( P T T)
I nter nati o nal n or malize d rati o (I N R) or pr ot hr o m bi n ti me ( P T)
Fi bri n o ge n – l ocal la b orat or y
Cli nic al c he mistr y – l ocal a n d ce ntral la b orat or yb
Ser u m c o nce ntr ati o ns of:

Ala ni ne a mi n otra nsferase ( A L T)

Al b u mi n

Al p ha- fet o pr otei n ( A F P; re q uire d o nl y f or 
patie nts wit h H C C)

Al kali ne p h os p hatase

As partate a mi n otra nsferase ( A S T)

A m ylase

Bicar b o nate

Bilir u bi n, direct

Bilir u bi n, t otal

Bl o o d urea nitr o ge n ( B U N) or bl o o d urea

C- reacti ve pr otei n

Calci u m

C hl ori de

Creati ni ne

Creati ne ki nase ( C K)

Ga m ma gl uta m yl tra nsferase ( G G T)

Gl uc ose, ra n d o m

Lactate de h y dr o ge nase ( L D H)

Li pase

P otassi u m

S o di u m

T otal pr otei n
T S H a n d free T 4 – ce ntral la b orat or y
Er yt hr oc yte se di me nt ati o n r ate ( E S R) – l ocal la b orat or y
C 3 a c o m ple me nt - ce ntral la b orat or y
C- A N C A/ P -A N C A/ Tr o p o ni n -I – ce ntral la b orat or y
T u m or m ar kers – l ocal la b orat or y
Uri n al ysis – l ocal la b orat or y
A micr osc o pic e xa mi nati o n is re q uire d f or a b n or mal res ults.  Micr osc o p y s h o ul d be use d as a p pr o priate t o i n vesti gate 
w h ite bl o o d cells a n d use t he hi g h-p o wer fiel d f or re d bl o o d cells.  Perf or m t he 2 4 -h o ur uri ne pr otei n a nal ysis if uri ne 
pr otei n is 2 + at baseli ne or d uri n g st u d y treat me nt

Bilir u bi n

Bl o o d

C ol or a n d a p peara nce

Gl uc ose

Ket o nes

p H

Pr otei n

S pecific gra vit y

Ur i ne le u k oc yte esterase
Pre g n a nc y test (f or fe male patie nts of c hil d beari n g p ote ntial) – l ocal la b orat or y

Ur i ne pre g na nc y test at a mi ni m u m se nsiti vit y of 2 5 I U/ L or e q ui vale nt u nits of β- h C G .  If uri ne pre g na nc y 
res ults ca n n ot be c o nfir me d as ne gati ve, a ser u m pre g na nc y test will be re q uire d
C CI
C CI


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 8 4
L Y 3 4 3 4 1 7 2
A b bre viati o ns:  D N A = de o x yri b o n ucleic aci d; I g = i m m u n o gl o b uli n; L Y = L Y 3 4 3 4 1 7 2; P K = p har mac o ki netic;
R B C = re d bl o o d cells; R N A = ri b o n ucleic aci d; T 4 = t h yr o xi ne; T S H = t h yr oi d-sti m ulati n g h or m o ne; W B C = 
w h ite bl o o d cells.
N ote:   St u d y  eli gi bilit y a n d decisi o ns a b o ut treat me nt will be base d o n l ocal la b orat or y res ults.
a
Ne utr o p hils re p orte d b y a ut o mate d differe ntial he mat ol o g y i nstr u me nts i ncl u de b ot h se g me nte d a n d ba n d 
f or ms. W he n a ma n ual differe ntial is nee de d t o re p ort t he ne utr o p hils, t he se g me nte d a n d ba n d f or ms s h o ul d be 
a d de d t o get her a n d rec or de d o n t he C R F, u nless t he C R F s pecificall y pr o vi des a n e ntr y fiel d f or ba n ds.
b
Perf or me d ce ntrall y (re q uire d) a n d l ocall y if cli nicall y i n dicate d.
c
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Appendix 3. Study Governance, Regulatory and  
Ethical Considerations 
Informed Consent
The investigator is responsible for: 

ensuring that the patient understands the nature of the study, the potential risks 
and benefits of participating in the study, and that their participation is voluntary 

ensuring that informed consent is given by each patient.  This includes obtaining 
the appropriate signatures and dates on the ICF prior to the performance of any 
study protocol procedures and prior to the administration of study treatment.

answering any questions the patient may have throughout the study and sharing in 
a timely manner any new information that may be relevant to the patient’s 
willingness to continue the patient’s participation in the study.

providing a copy of the ICF to the patient and retaining a copy of the signed ICF 
in the site file
Ethical Review
Documentation of ERB/IRB approval of the protocol and the ICF must be provided to Lilly 
before the study may begin at the investigative site(s).  Lilly or its representatives must approve 
all ICFs, including any changes made by the ERBs/IRBs, before it is used at the investigative 
site(s).  All ICFs must be compliant with the ICH guideline on GCP.
The study site’s ERB/IRB should be provided with the following:

the protocol, protocol amendments, and relevant protocol addenda, and the 
current IB and updates during the course of the study

ICF

other relevant documents (for example, curricula vitae, advertisements)
Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences International Ethical Guidelines 

the ICH GCP guidelines 

applicable laws and regulations
The investigator or designee will promptly submit the protocol to applicable ERB(s).


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Some of the obligations of Lilly will be assigned to a third party organization.
Investigator Information
Licensed physicians with a specialty in oncology will participate as investigators in this clinical 
study
Protocol Signatures
Lilly’s responsible medical officer will approve the protocol, confirming that, to the best of his 
or her knowledge, the protocol accurately describes the planned design and conduct of the study.  
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Final Report Signature
The CSR coordinating investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his or her knowledge, the report accurately describes the conduct and results 
of the study.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the CSR coordinating investigator.
Lilly’s responsible medical officer and statistician will approve the final CSR for this study, 
confirming that, to the best of his or her knowledge, the report accurately describes the conduct 
and results of the study.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

provide sponsor start-up training to instruct the investigators and study 
coordinators.  This training will give instruction on the protocol, the completion 
of the CRFs, and study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

review and verify data reported to detect potential errors 
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.


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Data Capture Systems
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data.  The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system.  The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
Additionally, clinical outcome assessment (COA) data (questionnaires, scales, self-reported diary 
data, rating scales etc.) will be collected by the subject/investigator site personnel, via a paper 
source document and will be transcribed by the investigator site personnel into the EDC system.
Data collected via the sponsor-provided data capture system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s).  Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/electronic transfers will be provided to the 
investigator for review and retention.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Study and Site Closures
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the 
ERB/IRB of the study site judges it necessary for medical, safety, regulatory, ethical, or other 
reasons consistent with applicable laws, regulations, and GCP.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 8 8
L Y 3 4 3 4 1 7 2
A p p e n di x 4.
S a m pli n g S c h e d ul e
P har mac o ki net ic, Im m u n o ge nicit y a n d Bio m ar ker sa m ples will be c ollecte d f or all patient s 
recei vi n g L Y 3 4 3 4 1 7 2.
Preferre d ti me wi n d o ws f or eac h P K/I G sa m ple c ollect i on are pr o vi de d i n t he ta bles i n t his 
secti on. W hil e best eff ort s h o ul d be d o ne t o dra w t he bl o o d sa m ples wit hi n t he ti me wi n d o ws 
pr o vi d e d, i t is more i m p orta nt t o e ns ure pre d ose sa m ple is act uall y  c ollecte d bef ore t he start of 
first i nf usio n  of t he da y a n d p ost d ose sa m ples are c ollecte d after t he res pective i nf usi on has 
c o mplete d. It is als o e q uall y i m p orta nt t o rec or d A C T U A L date a n d ti me o f bl o o d sa m ple 
c ollect i on o n t he Re q uisit i on F or m  AF T E R dra wi n g t he sa m ple (t hat is, d o n ot rec or d pla n ne d 
ti me of c ollecti on) a n d t o rec or d t he A C T U A L i nf usi o ns start a n d e n d dates a n d ti mes o n t he 
e C R F i n or der t o facilitate t he data a nal yses. 
Bl o o d sa m ple c ollect i on m u st be fr om t he o p p osite ar m t o t hat use d f or st u d y dr u g i nf usi on. If 
dr u g was a d mi nistere d via a ce ntral ve n o us cat heter, t he sa m ple c ollecti o n s h o ul d be fr om a 
differe nt site.
I n t he e ve nt of a n i nf usi on- relate d reacti o n (I R R), bl o o d sa m ples will be c ollecte d f or P K, I G a n d 
e x pl orat or y i m m u ne safet y a nal yses at t he f o ll owi n g ti me p oi nts, as cl ose as p ossi ble t o: (i) t he 
o nset of t he I R R, (ii) t he res ol ut i on of t he I R R, a n d (iii) 3 0 [ ± 3] da y s fol l owi n g t he I R R. 
 
C CI


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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points
Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Study 
Day
Sample Time 
(Relative to the 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
Baseline
28 days prior to 
C1D1
ECG:  2-3 sets of 
ECGs (each set is a 
triplicate), with 
approximately 15 
minutes between 
each set.d
Tumor tissue: 
required see Section
9.8.1.
X
X
X
Baseline
7 days prior to 
C1D1 
X
X
C1D1
1
0 hour predosee
PK, IG, and 
biomarkers
ECG:  2-3 sets of 
ECGs (each set is a 
triplicate), with 
approximately 15 
minutes between 
each set.d  Before 
blood draw. 
X
X
X
X
X
X
X
X
X
C1D1
1 hour post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Study 
Day
Sample Time 
(Relative to the 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C1D1
1
3 hours post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood drawd
X
X
X
X
X
C1D2
2
24 hours post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X
X
X
X
X
C1D4 
4
72 hours post 
LY3434172 infusionf
X
X
C1D8
8
168 hours post 
LY3434172 infusionf
X
X
X
X
X
X
X
C1D15
15
0 hour predosee
PK, IG, and 
biomarkers
X
X
X
X
X
X
C1D15
15
1 hour post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X (only 
cohort 
A1)
X 
(only 
A1)
X
X
C1D15
15
3 hours post 
LY3434172 
infusionf
X
X
C1D16
16
24 hours post 
LY3434172
infusionf
X
X (only 
cohort 
A1)
X 
(only 
A1)
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Study 
Day
Sample Time 
(Relative to the 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C1D22 
22
168 hours post 
LY3434172 infusionf
X
X (only 
cohort 
A1)
X
X 
(only 
A1)
X
C2D1
29
0 hour predosee
PK, IG, and 
biomarkers 
X
X
X
X
X
X
Xg
X
X
C2D1
29
1 hour post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X
X
C2D2
30
24 hours post 
LY3434172
infusionf
X
X
C2D15
43
0 hour predosee
X
X (only 
cohort 
A1)
X
X 
(only 
A1)
X
C2D15
43
1 hour post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X
X
C2D16
44
24 hours post 
LY3434172
infusionf
X
X
C3D1
57
0 hour predosee
PK, IG, and 
biomarkers
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Study 
Day
Sample Time 
(Relative to the 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C3D1
57
1 hour post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood draw.d
X
X
X
C4D1
85
0 hour predosee
PK and biomarkers
X
X
X
C4D1
85

1 hour post 
LY3434172 
infusion

ECG (single) 
X
C5D1
113
0 hour predosee
PK and biomarkers
X
X
X
C5D1
113

1 hour post 
LY3434172 
infusion
ECG (single)
X
C6D1
141
0 hour predosee
PK and biomarkers
X
X
X
C6D1
141

1 hour post 
LY3434172 
infusion
ECG (single)
X
C7D1; then, 
Q3 
(C10D1…)
169, 
197…
0 hour predosee
PK and biomarkers
X
X
X


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 9 3
L Y 3 4 3 4 1 7 2
P h ar m ac o ki netic, I m m u n o ge nicit y, Bi o m ar ker, a n d E C G C ollecti o n Ti me P oi nts C o h orts wit h Q 2 W D osi n g ( C o h ort A 1, A 2, A 3, A 4, A 5 , a n d A 6)
C ycle/ D a y
St u d y 
D a y
S a m ple Ti me 
( Rel ati ve t o t he 
E N D of L Y 3 4 3 4 1 7 2 
I nf usi o n)
P K a
I Ga
W h ole
Bl o o d
( P G x)
Bi o m ar ker C ollecti o n
E C G
Pl as m a
E x vi v o
W h ole
Bl o o d & 
P B M C b
Ser u m
Tiss ue
s P D- 1 
a n d 
s P D-L 1
St o ol c
W he n/if a n y 
D L T or D L T 
e q ui vale nt 
occ urs
A n y ti m e
X  
X
X
Last 
L Y 3 4 3 4 1 7 2 
d ose (if 
k n o w n) 
0 h o ur pre d ose e
P K, I G, a n d 
bi o mar kers
X  
X
X
3 0 da ys p ost 
last 
L Y 3 4 3 4 1 7 2 
d ose
A n y ti m ef
E C G (si n gle).  
Bef ore bl o o d dra w.
X
X
X
X
6 0 da ys p ost 
last 
L Y 3 4 3 4 1 7 2 
d ose
A n y ti m ef
E C G (si n gle).  
Bef ore bl o o d dra w.
X  
X
X
X
9 0 da ys p ost 
last 
L Y 3 4 3 4 1 7 2 
d ose
A n y ti m ef
E C G (si n gle).  
Bef ore bl o o d dra w.
X
X
X
Disease 
Pr o gressi o n
A n y ti m e bef ore start 
of ne xt a ntica ncer 
treat me nt.
Hi g hl y  
rec om me n de d
X
X 
( o pti o n
al)
X
A b bre viati o ns:  A D A = a nti dr u g a nti b o d y; C = C ycle; D = Da y; D L T = d ose -li miti n g t o xicit y; E C G = electr ocar di o gra m; I G = i m m u n o ge nicit y; 
I R R = i nf usi o n-relate d reacti o n; P G x = p har mac o ge n o mics; P K = p har mac o ki netics; Q = e ver y; W = wee k. 
a
I n t he e ve nt of a n i nf usi o n-relate d reacti o n (I R R), bl o o d sa m ples will be c ollecte d f or P K, I G a n d e x pl orat or y i m m u ne safet y a nal yses at t he f oll o wi n g ti me 
p oi nts, as cl ose as p ossi ble t o: (i) t he o nset of t he I R R, (ii) t he res ol uti o n of t he I R R, a n d (iii) 3 0 [ ± 3] da ys f oll o wi n g t he I R R. 
 
C CI


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
b
For exploratory research, including but not limited to immunophenotyping.
c    Fecal collections will begin at baseline with any new patients starting the trial at that time, and as the collection materials become available.
d
Triplicate ECGs: the 3 replicates should be approximately 1 minute apart, with all 3 replicates within a set conducted within a 5-minute timeframe.
e
Collect samples in the morning of infusion day prior to the start of first infusion of the day. 
f
The 1-, 3-, 24-, 72-, and 168-hour samples are relative to the END of the corresponding dosing event.  These samples must be collected after completion of 
the infusion.  Their sampling windows are ±15 minutes (1- and 3-hour), ± 4 hours (24-hour), ± 24 hours (72- and 168-hour), respectively.  The samples at 30, 
60, and 90 days post last LY3434172 dose have sampling windows of ±7 days.
g Tissue biopsy sample within 3 days prior to C2D1.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points
Cohorts with Q3W Dosing (Cohort A7 and A8)
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to the 
END of 
LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
Baseline
28 days prior to 
C1D1
ECG: 2-3 sets of 
ECGs (each set 
is a triplicate), 
with 
approximately 
15 minutes 
between each 
set.d  
Tumor tissue:  
required see 
Section 9.8.1
X
X
.X
Baseline
7 days prior to 
C1D1
X
X
C1D1
1
0 hour predosee
PK, IG, and 
biomarkers
ECG: 2-3 sets 
of ECGs (each 
set is a 
triplicate), with 
approximately 
15 minutes 
between each 
set. Before 
blood draw.d
X
X
X
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to the 
END of 
LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C1D1
1
1 hour post 
LY3434172 
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
X
X
X
C1D1
1
3 hours post 
LY3434172 
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
X
X
C1D2 
2
24 hours post 
LY3434172 
infusionf
ECG (triplicate) 
Before blood 
draw.d
X
X
X
X
X
X
C1D4 
4
72 hours post 
LY3434172 
infusionf
X
X
C1D8
8
168 hours post 
LY3434172 
infusionf
X
X
X
X
X
X
X
C1D15
15
336 hours post 
LY3434172 
infusionf
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to the 
END of 
LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C2D1
22
0 hour 
predosee
PK, IG, and 
biomarkers
X
X
X
X
X
X
X
C2D1
22
1 hour post 
LY3434172 
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
C2D1
22
3 hours post 
LY3434172 
infusionf
X
X
C2D2 
24
24 hours post 
LY3434172 
infusionf
X
X
C2D8
30
168 hours post 
LY3434172 
infusionf
X
X
X
X
C3D1
43
0 hour 
predosee
PK, IG, and 
biomarkers
X
X
X
X
X
X
Xg
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to the 
END of 
LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C3D1
43
1 hour 
postdose
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
C4D1
64
0 hour predosee
PK, and IG 
X
X
X
C6D1
0 hour predosee
PK:  collect 
sample for all 
patients
X
X
X
C8D1; then, 
Q4C (Cycle 
12…) 
148, 
232…
0 hour predosee
PK:  collect PK 
sample for all 
patients 
X
X
X
When/if any 
DLT or DLT 
equivalent 
occurs
Anytime
X
X
X
Last 
LY3434172 
dose (if 
known)
0 hour predosee
sample
PK, IG, and 
biomarkers
X
X
X
30 days post 
last 
LY3434172 
dose
Anytimef
ECG (single).  
Before blood 
draw.
X
X
X
X


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 9 9
L Y 3 4 3 4 1 7 2
P h ar m ac o ki netic, I m m u n o ge nicit y, Bi o m ar ker, a n d E C G C ollecti o n Ti me P oi nts C o h orts wit h Q 3 W D osi n g ( C o h ort A 7 a n d A 8)
C ycle/ D a y
St u d y 
D a y
S a m ple Ti me
( Rel ati ve t o t he 
E N D of 
L Y 3 4 3 4 1 7 2 
I nf usi o n)
P K a
I Ga
W h ole
Bl o o d
( P G x)
Bi o m ar ker C ollecti o n
E C G
Pl as m a
E x vi v o
W h ole
Bl o o d & 
P B M C b
Ser u m
Tiss ue
s P D-1 a n d 
s P D-L 1
St o ol c
6 0 da ys p ost 
last 
L Y 3 4 3 4 1 7 2 
d ose
A n y ti m ef
E C G (si n gle).  
Bef ore bl o o d 
dra w.
X  
X
X
X
9 0 da ys p ost 
last 
L Y 3 4 3 4 1 7 2 
d ose
A n y ti m ef
E C G (si n gle).  
Bef ore bl o o d 
dra w.
X
X
X
Disease 
pr o gesssi o n
A n y ti m e bef ore 
ne xt a ntica ncer 
treat me nt.
Hi g hl y  
r ec o m m e n de d
X
X 
( o pti o nal
)
X
A b bre viati o ns:  A D A = a nti dr u g a nti b o d y; C = C ycle; D = Da y; D L T = d ose -li miti n g t o xicit y; E C G = electr ocar di o gra m; I G = i m m u n o ge nicit y; 
I R R = i nf usi o n-relate d reacti o n; P G x = p har mac o ge n o mics; P K = p har mac o ki netics; Q = e ver y; W = wee k.
a
I n t he e ve nt of a n i nf usi o n-relate d reacti o n (I R R), bl o o d sa m ples will be c ollecte d f or P K, I G a n d e x pl orat or y i m m u ne safet y a nal yses at t he f oll o wi n g ti me 
p oi nts, as cl ose as p ossi ble t o: (i) t he o nset of t he I R R, (ii) t he res ol uti o n of t he I R R, a n d (iii) 3 0 [ ± 3] da ys f o ll o wi n g t he I R R.
 
b
F or e x pl orat or y researc h, i ncl u di n g b ut n ot li mite d t o i m m u n o p he n ot y pi n g.
c    Fecal c ollecti o ns will be gi n at baseli ne wit h a n y ne w pa tie nts starti n g t he trial at t hat ti me, a n d as t he c ollecti o n materials bec o me a vaila ble.
d
Tri plicate E C Gs: t he 3 re plicates s h o ul d be a p pr o xi matel y 1 mi n ute a part, wit h all 3 re plicates wit hi n a set c o n d ucte d wit hi n a 5 -mi n ute ti mefra me.
e
C ollect sa m ples i n t he m or ni n g of i nf usi o n da y pri or t o t he start of first i nf usi o n of t he da y . 
f
T he 1 -, 3 6-, 2 4-, 7 2-, 1 6 8- a n d 3 3 6 -h o ur sa m ples are relati ve t o t he E N D of t he c orres p o n di n g d osi n g e ve nt.   T he y m ust be c ollecte d after t he c o m pleti o n of 
the i nf usi o n.  T heir sa m pli n g wi n d o ws are ± 1 5 mi n utes ( 1- a n d 3-h o ur ), ± 4 h o urs ( 2 4-h o ur), ± 2 4 h o urs ( 7 2-, 1 6 8- a n d 3 3 6 -h o ur), res pecti vel y.  T he sa m ples 
at 3 0, 6 0, a n d 9 0 da ys p ost last L Y 3 4 3 4 1 7 2 d ose ha ve sa m pli n g wi n d o ws of ± 7 da ys.
g  Tiss ue bi o ps y s a m ple wit hi n 3 da ys pri or t o C 3 D 1 .
C CI


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Appendix 5.
Restricted and Prohibited Concomitant 
Medications
The table below describes the drug class and associated medications that will be restricted during 
the study treatment period.  Patients who, in the opinion of the investigator, require the use of 
any of the prohibited treatments for clinical management should be discontinued from the trial.  
Patients may receive other supportive therapy that the investigator deems to be medically 
necessary.  
Therapy
As Needed
Chronic Use
Exceptions or Conditions for Use
Antiplatelet therapy
Yes
Yes, with 
restrictions
Chronic use of aspirin up to 325 mg/day is permitted
Anticoagulation 
therapy
No
Yes, with 
restrictions
Patients who are on full-dose anticoagulation must be on 
a stable dose (minimum duration 14 days) of oral 
anticoagulant or low-molecular-weight heparin or 
similar agent.  If on warfarin, the patient must have an 
INR of ≤ 3 and no active bleeding or pathological 
condition present that carries a high risk of bleeding (for 
example, tumor involving major vessels or known 
varices).
Colony-stimulating 
factors
Yes
No
Follow local guidelines.  No prophylactic use
Erythroid growth 
factors
Yes
No
Follow local guidelines
Experimental 
medicines or 
investigational agents
No
No
Glucocorticoids
Yes, with 
restrictions
Yes, with 
restrictions
Use of corticosteroids for the management of 
investigational product-related AEs or in patients with 
contrast allergies is acceptable.  A temporary course of 
corticosteroids will be allowed for other indications, at 
the discretion of the principal investigator (for example, 
chronic obstructive pulmonary disease, radiation, 
nausea).  Systemic corticosteroids doses should not 
exceed 10 mg/day of prednisone or equivalent (except as 
stated otherwise in this protocol).
The use of physiologic doses of corticosteroids may be 
approved after consultation with Lilly.
The use of topical, ophthalmic, inhaled, and intranasal 
corticosteroids is permitted.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Therapy
As Needed
Chronic Use
Exceptions or Conditions for Use
Immunosuppressive 
medications other 
than glucocorticoids 
(including, but not 
limited to 
methotrexate, 
azathioprine, and 
TNF-α blockers)
No
No
Use of immunosuppressive medications for the 
management of AEs related to LY3434172 or in patients 
with contrast allergies is acceptable
NSAIDs
Yes
No
See guidance for aspirin on the “antiplatelet therapy” 
line above.
Chronic use of other NSAIDs is not permitted.  
However, in certain medical situations, NSAIDs may be 
the best treatment option (for example, for pain 
management) and are therefore permissible as needed. 
Abbreviations:  AE = adverse event; INR = international normalized ratio; NSAIDs = nonsteroidal 
anti-inflammatory drugs; TNF = tumor necrosis factor.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Appendix 6. Hepatic Monitoring Tests for
Treatment-Emergent Abnormality
Selected tests may be obtained in the event of a treatment emergent hepatic abnormality and may 
be required in follow up with patients in consultation with the Lilly CRP/CRS.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin (HGB)
Hematocrit (HCT)
Hepatic Coagulationa
Erythrocytes (RBC)
Prothrombin Time (PT)
Leukocytes (WBC)
Prothrombin Time, INR
Neutrophilsb
Lymphocytes
Hepatic Serologiesa,c
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets (PLT)
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
Alanine aminotransferase (ALT)
Recommended Autoimmune Serology:
Aspartate aminotransferase (AST)
Anti-nuclear antibodya
Gamma-glutamyl transferase (GGT)
Anti-smooth muscle antibodya
Creatine phosphokinase (CPK)
Anti actin antibodya
Abbreviations:  Ig = immunoglobulin; INR = International Normalised Ratio; RBC = red blood cells; WBC = white 
blood cells.
a
Assayed by Lilly-designated laboratory.
b
Neutrophils reported by automated differential hematology instruments include both segmented and band 
forms. Whenever a manual differential is needed to report the neutrophils, the segmented and band forms should 
be added together and recorded on the CRF, unless the CRF specifically provides an entry field for bands.
c
Reflex/confirmation dependent on regulatory requirements and/or testing availability.


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Appendix 7. Creatinine Clearance Formula
Note:  This formula is to be used for calculating creatinine clearance (CrCl) from local 
laboratory results only.  
For serum creatinine concentration in mg/dL:
CrCl =
(140 – agea) (wt)    0.85 (if female), or 1.0 (if male)
(mL/min) 
72 serum creatinine (mg/dL)
For serum creatinine concentration in mol/L:
CrCl  =
(140 – agea) (wt)  0.85 (if female), or 1.0 (if male)
(mL/min)
               0.81 x serum creatinine (µmo/L)
a age in years, weight (wt) in kilograms.
Reference:  Cockcroft and Gault 1976.


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Appendix 8.
Dose-Finding Algorithm of the Modified 
Toxicity Probability Interval (mTPI-2) Method Showing 
Number of Patients Treated
Source:  Guo et al. 2016.
The number of patients dosed at a given dose level is shown in the columns (X-axis), while the 
number of DLTs experienced is shown in the rows (Y-axis).  The rules in this figure will be used 
for each dose level evaluated; the patient numbers and DLTs do not carry over from cohort to 
cohort.  By locating the intersection of the number of patients dosed and the number of DLTs, 1 
of 4 predefined rules is used:

E:  Escalate the dose

S:  Stay at the same dose

D:  De-escalate the dose

DU:  De-escalate the dose due to unacceptable toxicity.  The dose cannot be re-escalated 
to this dose level at a future point in the escalation.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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For example, within a cohort:

If 1 of 3 patients experiences a DLT, stay at the same dose (see “S” in column 3, row 1).  
The fourth patient must be treated at the same dose level.

If 1 of 6 patients experiences a DLT, escalate the dose (see “E” at column 6, row 1).

If 2 of 3 patients experience a DLT the dose to treat the next patient is de-escalated (see 
“D” at column 3, row 2).

If 5 of 7 patients experience a DLT, the dose is determined to be unacceptably toxic, and 
the previous dose is defined as the MTD.


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Appendix 9.
Definition of Woman of Childbearing Potential
Definitions:
Woman of Childbearing Potential (WOCBP)
A female is not considered to be of childbearing potential due to surgical sterilization confirmed 
by medical history (at least 6 weeks post-surgical bilateral oophorectomy with or without 
hysterectomy or tubal ligation) or menopause.
Menopausal women include women with either:
a.
spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as 
anorexia nervosa, and not taking medications during the amenorrhea that induced the 
amenorrhea (for example, oral contraceptives, hormones, gonadotropin-releasing hormone, 
antiestrogens, selective estrogen receptor modulators, or chemotherapy), or
b. spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level 
>40 mIU/mL.
For individuals with permanent infertility due to an alternate medical cause other than the above,
(for example, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
Exceptions to those listed above would be if female and of childbearing potential, has a negative 
serum or urine pregnancy test within 7 days prior to the first dose of study medication, agrees to 
use a highly effective method of birth control during the study and for 6 months following the 
last dose of the study drugs, and is not breastfeeding.  If the urine pregnancy test is positive or 
cannot be confirmed as negative, a serum pregnancy test will be required.


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Appendix 10. Protocol Amendment J1E-MC-JZEA(b) 
Summary A Phase 1 Study of LY3434172, a Bispecific 
Antibody Administered as a Monotherapy in Advanced 
Solid Tumors
Overview
Protocol J1E-MC-JZEA(a), A Phase 1 study of LY3434172, a bispecific antibody administered 
as a monotherapy in advanced solid tumors, has been amended.  The new protocol is indicated 
by Amendment (b) and will be used to conduct the study in place of any preceding version of the 
protocol.
The overall changes and rationale for the changes made to this protocol are as follows:

The following phrase was made applicable for Cohorts A1 to A5/A6: “Once 
dose-limiting toxicity (DLT) period is completed for respective Cohorts A1 to A5/6 up to
approximately 12 to 15 additional patients may be added to two dose levels selected from 
these cohorts.” Corresponding revisions were made to Synopsis (Overall Design), Section 
5.1 (Overall Design), Section 7.1 (Treatment Administered), Section 10.1 (Sample Size 
Determination), and Section 10.3.4 (Interim Analyses).

A clarification of the 4-hour observation period and the sampling times relative to
infusion time was made throughout the document.  All observation periods and post-dose 
sampling times are now relative to the end of LY3434172 administration/infusion.

A correction to the timing of tumor imaging for Cohorts A7 and A8 after Cycle 1 Day 1 
was made. For Cycle 3 and beyond, Day 8 visits were deleted from the Schedule of 
Activities for these cohorts, since there are no infusions and sample collections for the D8 
visits.

A correction to vital signs collected during the post study treatment schedule was made to 
include oxygen saturation.

A change was made to exclusion criterion 14 in Section 6.2 to clarify active hepatitis and 
active tuberculosis.

A statement about repeating screening tests was deleted from Section 6.4.

A clarification that anaphylaxis will be considered a DLT was made to Section 7.2.2.2.1
and a clarification that study treatment will be immediately and permanently discontinued 
was added to Table JZEA 9.

Additional standard safety monitoring language was added to Section 9.4.2.

Stool sample collections were added to Appendix 4 and clarification of the timing of 
predose and post dose samples was added to the footnotes.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1 0 8
L Y 3 4 3 4 1 7 2
R e vi s e d Pr ot o c ol S e cti o n s
N ote:
All deleti o ns ha ve bee n i de nt ifie d b y striket hr o u g hs .
All a d ditio ns ha ve bee n i de nt ifie d b y t he use of u n dersc ore .
Secti o n 1. S y n o psis
O ver all Desi g n:
St u d y  J 1 E-M C -J Z E A (J Z E A) is a mul tice nter, n o nra n d o mize d, o pe n -label P hase 1 st u d y  in 
pati e nts wit h a d va nce d s oli d t u m ors.
P hase 1 st u d y  will assess t he safety a n d t olera bilit y of L Y 3 4 3 4 1 7 2, a d mi nistere d as a 
m o n ot hera p y  in pat ient s wit h select a d va nce d s oli d t u m ors. St u d y  J Z E A will facilitate a 
t hor o u g h safet y e val uat i on a n d e x pl orat i on of p har mac o ki net ics (P K ) a n d p har mac o d y na mics 
effects f or t he e ver y t w o-wee k ( Q 2 W) d osi n g sc he d ule ( C o h orts A 1 t o A 6) .  Once d ose -li miti n g 
t o xicit y ( D L T) perio d is c o m plete d f or res pecti ve C o h orts A 1 t o A 5 / 6 u p t o a p pr o xi matel y 1 2 t o 
1 5 a d ditio n al  pat ient s ma y be a d de d t o t w o d ose le vels selecte d fr o m C o h orts A 4, A 5/ 6. t hese 
c o h orts.  
…
Tre at me nt Ar ms a n d D ur ati o n:
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J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Table JZEA.1
Baseline and On-Study Treatment Schedule of Activities (Cohort 
A1, A2, A3, A4, A5, and A6)
Baseli
ne
(Day 
Relativ
e to 
C1D1)
Cycle = 28 days
Instructions
Cycle 1
(±3 
days)
Cycle 
2
(±3 
days)
Cycle 
3
(±3 
days)
Cycle 
4-n
(±3 
days)

2
8
7
D1
D
1
5
D
1
D
15
D
1
D
1
5
D
1
D
15
Vital signs 
X
X
X
X
X
X
X
X
X
Measure vital signs (height (at baseline), 
weight, temperature, blood pressure, 
pulse rate, oxygen saturation, and 
respiration rate) as follows (±5 minutes):
In Cycles 1 through 3:
within 15 minutes prior to each 
LY3434172 infusion
every 15 minutes during each 
LY3434172 infusion
at the end of each LY3434172 infusion
A 4-hour observation period (See Section 
5.1.1 and 7.4) from the end of following the 
end of LY3434172 administration will 
occur in Cycles 1 to 3.
every 30 (±5) minutes for the first 
hour and 60 (±5) minutes thereafter 
during the 4-hour observation period
In Cycle 4 and beyond, if the patient 
has not experienced an infusion-
related reaction or other infusion-
related AE:
up to 15 minutes prior to each 
LY3434172 infusion
at least once during each LY3434172 
infusion
at the end of each LY3434172 infusion
Administer 
LY343417
2
X
X
X
X
X
X
X
X
LY3434172 will be administered as an IV 
infusion over approximately 60 minutes, 
depending on dose level (doses <100 mg 
may require bolus IV injection 
administration over approximately 5 to 10 
minutes).  A 4-hour observation period from 
the start offollowing the end of LY3434172 
administration will occur in Cycles 1 to 3.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Table JZEA.2
Baseline and On-Study Treatment Schedule of Activities (Cohort 
A7 and A8)
Baseli
ne
(Day 
Relativ
e to 
C1D1)
Cycle = 21 days
Instructions
Cycle 1
(±3 
days)
Cycle 
2
(±3 
days)
Cycle 
3
(±3 
days)
Cycle 
4-n
(±3 
days)

2
8
7
D1
D
8
D
1
D
8
D
1
D
8
D
1
D
8
Procedure
Physical 
examinatio
n
X
X
X
X
X
X
X
X
X

D1 visit should be completed by a 
physician.

Should include palpable tumor 
measurement.
Vital signs 
X
X
X
X
X
Measure vital signs (height (at baseline), 
weight, temperature, blood pressure, 
pulse rate, oxygen saturation, and 
respiration rate) as follows (±5 minutes):
In Cycles 1 through 3:
up to 15 minutes prior to each 
LY3434172 infusion
every 15 minutes during each 
LY3434172 infusion
at the end of each LY3434172 infusion
A 4-hour observation period (See Section 
5.1.1 and 7.4) fromfollowing the end of 
LY3434172 administration will occur in 
Cycles 1 to 3.
every 30 (±5) minutes for the first 
hour and every
60 (±5) minutes thereafter during the 
4-hour observation period
ECOG PS
X
X
X
X
X
X
X
X
X
During study treatment, perform 3 days 
prior to D1 of each cycle.
ECHO
X
See 
instruct
ions
Perform locally, at baseline, at Cycle 4 Day 
1, and as clinically indicated.
ECG
See Appendix 4 for ECG collection 
instructions
Blood tumor 
markers
X
X
X
X
X
As appropriate for particular tumor types 
(local testing).  For example, include alpha-
fetoprotein for patients with HCC.
Hematology
X
X
X
X
X
X
X
X
X
See Appendix 2


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Clinical 
chemistry 
X
X
X
X
X
X
X
X
X
See Appendix 2
Tumor 
imaging/
assessment
X
X
S
ee 
In
st
ru
ct
io
ns
Perform locally according to RECIST 
1.1, using the same method at each 
assessment
Perform as scheduled, even if study 
treatment is delayed or omitted, except 
when deemed not feasible in the opinion 
of the investigator because of the 
patient’s clinical status.
Note:  After C1D1, perform Q8WQ6W
(±7 days) according to RECIST 1.1 for 
the first year, until a discontinuation 
criterion is met. If radiologic imaging 
verifies an initial assessment of PD, 
apply RECIST 1.1 with confirmatory 
scan for disease progression (Section
9.1.1).
If the patient is still on study treatment 
after 1 year, perform tumor imaging 
approximately every 12W.
Sample 
collection
See Appendix 4 for pharmacodynamics, 
pharmacokinetics, immunogenicity, 
pharmacogenetics, tumor tissue, and other 
biomarkers.
Administer 
LY343417
2
X
X
X
X
LY3434172 will be administered as an IV 
infusion over approximately 60 minutes, 
depending on dose level (doses <100 mg 
may require bolus IV injection 
administration approximately 5 to 10 
minutes). A 4-hour observation period 
fromfollowing the startend of LY3434172 
administration will occur in Cycles 1 to 3.


J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1 1 2
L Y 3 4 3 4 1 7 2
T a bl e J Z E A . 3.
P o st st u d y Tr e at m e nt S c h e d ul e of A cti viti e s ( All P art s)
F oll o w -U p Visit
( ± 7 da ys)
I nstr ucti o ns
S h ort -Ter m a
L o n g -
Ter m
( Q9 0 D) b
Visit
3 0-
D a y
6 0 -
D a y
9 0-
D a y
8 0 1 
8 0 2 
8 0 3
8 0 4 t o 
8 X X
Pr oce d ure
P h y sical 
e xa mi nati o n
X
I ncl u di n g wei g ht a n d vital si g ns (te m perat ure, bl o o d 
press ure, p ulse rate, o x y ge n sat urati o n , a n d res pirati o n 
rate)
5. 1. 
O ver all Desi g n
…
T o facilitate a t h or o u g h safet y  e val uati on a n d e x pl orati o n of P K a n d p har mac o d y na mics effects
of t he e ver y t w o wee k ( Q 2 W) d osi n g sc he d ule ( C o h orts A 1 t o A 6) will be e x pl ore d.  O nce 
d ose -li miti n g t o xicity ( D L T) perio d is c o m plete d f or res pecti ve C o h orts A 1 t o A 5 / 6 u p t o
a p pr o xi matel y 1 2 t o 1 5 a d diti o nal pat ient s ma y be a d de d t o t w o d ose le ve ls selecte d fr om 
C o h orts A 4, A 5/ 6 t hese c o h orts (see Fi g ure J Z E A. 1 ). Aft er e val uat i n g P K/p har mac o d y na mic data 
fr om t hese c o h orts, a n y d oses fr o m t he d ose escalatio n ra n ge c o ul d be use d i n or der t o c o ver t he 
e nt ire pre dicte d biol o gicall y  effecti ve d ose ( B E D) a n d all o w f or u ncertai nty ar o u n d it (see 
S ectio n 5. 5). 
 
 
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J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1 1 3
L Y 3 4 3 4 1 7 2
5. 1. 1.
D ose Esc al ati o n
…
 
 
 O nce D L T peri o d of  28 da y s for Q 2 W , e xce pt C o h ort A 1 
wi t h 4 2 da y D L T, is c om p lete d f or res pecti ve d ose le vels wit hi n C o h orts A 1 t o A 5/ A 6,
C o h orts A 4, A 5, a n d A 6 ca n be e x pa n de d bet wee n 1 2 a n d 1 5 patie nts i n t otal at t wo d ose l e vels, 
yet t o be deter mi ne d b ut will be selecte d fr om t hese t hree c o h orts , ca n be e x pa n de d bet wee n 1 2 
a n d 1 5 patie nts i n t otal. P har mac o ki net ic, p har mac o d y na mic a n d sa fety data e val uate d d uri n g 
t he c o urse of t he d ose escalat i on will  be use d t o select t hese t w o d ose le vels. T he p ur p ose of 
e x pa n di n g C o h orts A 4, A 5, a n d A 6 t o a d ditio nal  1 2-1 5 patie nts is t o f urt her i nf or m safety,  P K 
a n d p har mac o d y na mics.  T hese c o h orts wil l c o nti n ue t o e nr oll w hile i nteri m a nal ysis (I A) is 
o n g oi n g.
5. 2.
N u m ber of P atie nts
…
A p pr o xi matel y  1 5 t o 2 0 patie nts will be e nr olle d i n Q 2 W d ose escalati o n, a p pr o xi matel y 1 2 t o 
1 5 a d ditio n al  pat ient s ma y be a d de d t o t w o d ose le vels selecte d f r o m C o h orts A 4, A 1 t o A 5/ A 6 
aft er s electe d d ose le vel has cleare d t he D L T perio d f or a de q uate assess me nt of safety a n d 
e x pl orat i on of P K a n d p har mac o d y na mic effects.   
6. 1
I ncl usi o n Criteri a
P ati e nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if t he y meet all t he f o ll owi n g cri t eria:
[ 1]
Mela n o ma, N S C L C, s q ua m o us cell carci n oma of t he hea d a n d nec k ( S C C H N), 
ur ot helial ca ncer, gastric ca ncer, c ol orectal ca ncer, biliar y tract ca ncer, a nal ca ncer , 
nas o p har y n geal ca ncer , es o p ha geal ca ncer , S C L C, o varia n ca nc er, mes ot heli o ma, 
pa n -t u mor M SI hi  s oli d t u mors, he pat ocell ular carci n o ma , mer kel cell ca ncer , 
c uta ne o us s q ua m o us cell carci n o ma, e n d o met rial ca ncer, breast ca ncer, cer vical 
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J 1 E -M C -J Z E A( b) P h a s e 1 O n c ol o g y Pr ot o c ol
P a g e 1 1 4
L Y 3 4 3 4 1 7 2
ca ncer, t h yr oid ca ncer , sali var y ca ncer, a n d pr ostate ca ncer w h o ha ve recei ve d at least 
o ne li ne of sta n dar d s yste mic t hera p y  for t h ei r res pecti ve t u mor t y pe i n t he m etastatic 
setti n g with pr o gressi ve l ocall y a d va nce d or metastatic disease a n d t hat is n ot 
a me na ble/resista nt t o a p pr o ve d sta n dar d -of -care t hera p y.  Prior a nti -P D -1 a n d a nti -
P D -L 1 all o we d if t he y recei ve d a n ot her t hera p y  im me diatel y pri or t o t his st u d y  or 
t here has bee n a la pse of a p pr o xi matel y ≥9 0 da ys fr o m  prior t hera p y .  If patie nts 
recei ve d pri or a nti-P D -1 or a nti -P D -L 1, t he f o ll owi n g cri t eria nee d t o be met:
6. 2
E xcl usi o n Criteri a
P ati e nts will be e xcl u de d fr o m t he st u d y if t he y meet a n y of t h e fol l owi n g criteria:
[ 1 4] Ha ve a seri o us c o nc o mit a nt s yste mic dis or der t hat, i n t he o pi ni o n of t he i n vest i gat or, 
w o ul d c o m pr o mise t he pati e nt’s a bilit y t o a d here t o t he pr ot oc ol, s u c h as t he 
f oll owi n g:
b.
acti ve he pat itis B or C vir us i nfecti on acc or di n g t o l ocal sta n dar ds (scree ni n g n ot 
re q uire d) (e. g., wit h n o e vi de nce of k n o w n p osi ti ve he patitis B s urface a nti ge n or 
k n o w n p osit i ve he patitis C a nti b o d y a n d q ua ntitati ve he pat itis C R N A greater t ha n 
t he lo wer li mit of detecti o n of t he assa y ).
c.
c urre nt acti veor k n o w n hist or y  of t u berc ulosis
6. 4 .
Scree n F ail ures
Re peat i n g lab orat or y  tests (i ncl u di n g E C Gs) t hat di d n ot meet eli gi bility crit eria d uri n g t he 
2 8- d a y  baseli ne-scree ni n g peri o d d oes n ot c o nstit ute rescree ni n g.  H o we ver, la b orat or y tests ma y 
n ot be re peate d m ore t ha n t wice. If t he res ults of a re peate d la b orat or y test meet t he eli gi bilit y 
criteria, t hat la b orat or y t est must be re peate d a gai n t o c o nfir m eli gi bilit y.
7. 1 .
Tre at me nt A d mi nistere d
L Y 3 4 3 4 1 7 2 will be a d mi nistere d as a n I V i nf usi o n o ver a p pr o xi matel y  6 0 mi n utes, de pe n di n g o n 
d ose l e vel ( d oses < 1 0 0 m g m a y re q uir e b olus I V i nf usi o n, a p pr o xi matel y  o ver 5 t o 1 0 mi n utes).  
A 4 -h o ur o bser vat i on peri o d fr om t he start of f oll owi n g t he e n d of L Y 3 4 3 4 1 7 2 a d mi nistrati o n 
will occ ur i n C ycles 1 t o 3.
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J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
7.2.1. Selection and Timing of Doses
…
The first study treatment will be administered within 7 days after the patient is assigned to a 
treatment cohort.  There should be a minimum of 14 days between doses of study drug for all 
cohorts in Q2W schedule and 21 days between doses of study drug for the Q3W schedule.
However, if there is a delay due to holiday, weekend, bad weather, or other unforeseen 
circumstances, a flexibility of ±3 days is permitted.
7.2.2.2.1.
Events That Are Not Considered to Be DLTs
The following events will not be considered to be DLTs:
…

First occurrence of Grade 3 infusion-related reaction (IRR) during infusion of LY3434172, if 
both of the following criteria are met:
o
the patient did not receive corticosteroid prophylaxis, and
o
the Grade 3 IRR resolves within 6 hours with appropriate clinical management
o
If symptoms reappear, the event would be considered a DLT.
o
If this first occurence is anaphylaxis of any grade, the event would be considered a DLT.
7.4.
Dose Modification
…
A 4-hour observation period from the start offollowing the end of LY3434172 administration 
will occur in Cycles 1 to 3. During observation period, patients treated with LY3434172 should 
be closely monitored for signs and symptoms indicative of an infusion-related reaction by 
medical staff from the start of the infusion, in an area where emergency medical resuscitation 
equipment and other agents (epinephrine, prednisolone, or equivalents, etc.) are available.  
LY3434172 infusion-related reactions will be defined according to the Common Terminology 
Criteria for Adverse Events (CTCAE), version 5.0 definition of IRRs.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Table JZEA.9.
Management of Infusion-Related Reactions (IRR)
Grade
Management
2
First occurrence  
Immediately and permanently discontinue treatment if hypersentivity reaction is 
due to anaphylaxis of any grade.
Stop the infusion for other infusion-related reactions.
1.    If resolved to baseline or Grade 1 within 1 hour after stopping the infusion
a.     restart the infusion at 50% of the original rate (e.g., reduce from 
100 mL/hr to 50 mL/hr)
2.   If NOT resolved to Grade 0 or 1 within 1 hour after stopping the infusion:
a.    delay study treatment until the symptoms resolve in ≤48 hours, and 
b.    premedicate prior to the next scheduled dose.  Premedication should be 
administered 1.5 hours (±30 minutes) prior to the LY3434172 infusion 
with diphenhydramine (or other antihistamine), acetaminophen (or other 
antipyretic), steroids, etc., at the discretion of treating physician.
9.1.
Efficacy Assessments
…
During Study Treatment: 

Performed every 8 weeks (±7 days) for the 28-day cycle cohorts and every 6 weeks (±7 
days) for the 21-day cycle cohorts, by the investigator, with confirmatory assessment 
obtained at the next routine scheduled imaging time point (See Section 9.1.1.).
9.4.2. Safety Monitoring
Lilly will review safety data on a cohort by cohort basis and periodically review evolving 
aggregate safety data within the study by appropriate methods. 
Lilly has systematic and robust internal processes in place that ensure safety surveillance of 
development compounds in line with the US Food and Drug Administration (FDA)’s 
expectations for safety assessment committees (SAC) (FDA Draft Guidance: “Expansion 
Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and 
Biologics”; FDA Draft Guidance: “Master Protocols: Efficient Clinical Trial Design Strategies to 
Expedite Development of Oncology Drugs and Biologics”; FDA Draft Guidance: “Safety 
Assessment for IND Safety Reporting”; FDA Guidance: “Safety Reporting Requirements for 
INDs and BA/BE Studies”). This includes processes with clearly described roles and 
responsibilities that are owned by Lilly’s Global Patient Safety organization.  These processes 
are designed to monitor the evolving safety profile (i.e. review of cumulative SAEs, other 
important safety information) by designated cross-functional teams in a timely manner at pre-
defined intervals or on an ad-hoc basis. In addition, a dedicated process may be used to perform 
unblinded comparisons of event rates for SAEs as necessary.  
This system ensures that the accumulating safety data derived from individual and multiple trials 
across a development program is reviewed on a regular basis and that important new safety 
information such as the need for protocol modification or other relevant safety related material is 
identified and  communicated to regulators and investigators appropriately and in a timely 


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
fashion.  An internal review of aggregate safety data occurs on at least a quarterly basis or more 
frequently, as appropriate.  Any serious adverse reactions are reported within the required 
timeline for expedited reporting.
In addition to annual periodic safety updates and to further inform investigators, a line listing 
report of SUSARs is created and distributed to investigators on a biannual (twice yearly) basis. 
Any significant potential risk/safety concerns that are being monitored as well as any results 
being reported in other periodic reports for the compound; SAC decisions; and other significant 
safety data (for example, nonclinical or clinical findings, removal of serious adverse reactions) 
are included in the report.
9.8.2
Other Samples for Biomarker Research
The following samples for biomarker research will be collected for the purposes described in 
Section 9.8, and as specified in Appendix 4, where local regulations allow. 
…

Stool (when applicable, stool specimens may be collected for microbiome 
analyses)
10.1. Sample Size Determination
…
The total sample size in Cohorts A1 to A5/A6 will be determined by the incidence of DLTs.  The 
RP2D could be chosen after the corresponding Q2W cohorts have been enrolled.  After the DLT 
period (Cohorts A1 to A5/A6) is completed, Cohorts A4, A5, or A6 may includean additional 
enrollment of approximately12 to 15 patients at two selected dose levels selected from these 
cohorts will be enrolled for adequate assessment of safety and exploration of PK and 
pharmacodynamic effects.
10.3.4.  Interim Analyses
…
An interim analyses will be performed after all patients from cohorts A1 to A5/6 have completed 
the DLT evaluation period. Additional enrolment of 12-15 patients tofrom these cohorts A4 to 
A5/6at two dose levels (yet to be determined) can continue during IA.
Appendix 2 Clinical Laboratory Tests
b
Performed centrally (required)only, unless and locally laboratory isif clinically indicated.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Appendix 4 Sampling Schedule
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points
Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
Baseline
28 days prior to C1D1
ECG:  2-3 sets of ECGs 
(each set is a triplicate), 
with approximately 15 
minutes between each 
set.d
Tumor tissue: required 
see Section 9.8.1.
X
X
X
Baseline
7 days prior to C1D1 
X
X
C1D1
1
0 hour predosee
PK, IG, and 
biomarkers:  collect 
samples in the morning 
of infusion day prior to 
start of first infusion of 
the day
ECG:  2-3 sets of ECGs 
(each set is a triplicate), 
with approximately 15 
minutes between each 
setd.set.d  Before blood 
draw. 
X
X
X
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C1D1
1 hour post 
LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X
X
X
X
X
C1D1
1
3 hours post 
LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood drawd
X
X
X
X
X
C1D2
2
24 hours post 
LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X
X
X
X
X
C1D4 
4
72 hours post LY3434172 
infusioncinfusionf
X
X
C1D8
8
168 hours post 
LY3434172 
infusioncinfusionf
X
X
X
X
X
X
X
C1D15
15
0 hour 
predosepredosee
PK, IG, and 
biomarkers:  collect 
samples 2 hours prior 
to start of first infusion 
of the day
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C1D15
15
1 hour post LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X (only 
cohort 
A1)
X 
(only 
A1)
X
X
C1D15
15
3 hours post 
LY3434172 
infusioncinfusionf
X
X
C1D16
16
24 hours post start of 
LY3434172 infusionf
X
X (only 
cohort 
A1)
X 
(only 
A1)
X
C1D22 
22
168 hours post 
LY3434172 
infusioncinfusionf
X
X (only 
cohort 
A1)
X
X 
(only 
A1)
X
C2D1
29
0 hour predosee
PK, IG, and 
biomarkers:  collect 
samples in the morning 
of infusion day prior to 
start of first infusion of 
the day
X
X
X
X
X
X
XeXg
X
X
C2D1
29
1 hour post LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X
X
C2D2
30
24 hours post start of 
LY3434172 infusionf
X
X
C2D15
43
0 hour 
predosepredosee
X
X (only 
cohort 
A1)
X
X 
(only 
A1)
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C2D15
43
1 hour post 
LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X
X
C2D16
44
24 hours post 
LY3434172 infusionf
X
X
C3D1
57
0 hour predosee
PK, IG, and 
biomarkers: collect 
samples in the morning 
of infusion day prior to 
start of first infusion of 
the day
X
X
X
X
X
X
C3D1
57
1 hour post 
LY3434172 
infusioncinfusionf
ECG (triplicate) Before 
blood draw.d
X
X
X
C4D1
85
0 hour predosee
PK and biomarkers
X
X
X
C4D1
85

1 hour post 
LY3434172 infusion 

ECG (single) 
X
C5D1
113
0 hour predosed
PK and biomarkers
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
C5D1
113

1 hour post 
LY3434172 infusion 
ECG (single)
X
C6D1
141
0 hour predosee
PK and biomarkers
X
X
X
C6D1
141

1 hour post 
LY3434172 infusion 
ECG (single)
X
C4D1C7D1; 
then, Q3 
(C7…)C10D
1…)
85, 
169, 
197
…
0 hour predosee
PK and biomarkers:  
collect samples in the 
morning of infusion day 
prior to start of first 
infusion of the day
X
X
X
When/if any 
DLT or DLT 
equivalent 
occurs
Anytime
X
X
X
Last 
LY3434172 
dose (if 
known) 
0 hour predosee
PK, IG, and 
biomarkers:  collect 
samples in the morning 
of infusion day prior to 
start of first infusion of 
the day.
X
X
X
30 days post 
last 
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  Before 
blood draw.
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q2W Dosing (Cohort A1, A2, A3, A4, A5, and A6)
Cycle/Day
Stud
y 
Day
Sample Time 
(Relative to STARTthe 
END of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 
and 
sPD-L1
Stoolc
60 days post 
last 
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  Before 
blood draw.
X
X
X
X
90 days post 
last 
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  Before 
blood draw.
X
X
X
Disease 
Progression
Anytime before start of 
next anticancer treatment.
Highly recommended
X
X 
(option
al)
X
c    Fecal collections will begin at baseline with any new patients starting the trial at that time, and as the collection materials become available.
d
Triplicate ECGs: the 3 replicates should be approximately 1 minute apart, with all 3 replicates within a set conducted within a 5-minute timeframe.
e
Collect samples in the morning of infusion day prior to the start of first infusion of the day. 
f
The 1-, 2-, 43-, 24-, 72-, 120- and 168-hour samples are relative to the STARTEND of the corresponding dosing event.  These samples must be collected after 
completion of the infusion.  Their sampling windows are ±15 minutes (1-, 2-, and 43-hour), ± 4 hours (24-hour), ± 24 hours (72-, 120-, and 168-hour), 
respectively.  The samples at 30, 60, and 90 days post last LY3434172 dose have sampling windows of ±7 days.
g
Tissue biopsy sample within 3 days prior to C2D1.


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points
Cohorts with Q3W Dosing (Cohort A7 and A8)
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
Baseline
28 days prior to 
C1D1
ECG: 2-3 sets of 
ECGs (each set 
is a triplicate), 
with 
approximately 
15 minutes 
between each 
set.d  
Tumor tissue:  
required see 
Section 9.8.1
X
X
X
Baseline
7 days prior to 
C1D1
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C1D1
1
0 hour predosee
PK, IG, and 
biomarkers:  
collect samples 
in the morning 
of infusion day 
prior to start of 
first infusion of 
the day
ECG 2-3 sets of 
ECGs (each set 
is a triplicate), 
with 
approximately 
15 minutes 
between each 
set. Before 
blood draw.d
X
X
X
X
X
X
X
X
X
C1D1
1
1 hour post 
LY3434172 
infusionc  
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C1D1
1
3 hours post 
LY3434172 
infusioncinfusi
onf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
X
X
C1D2 
2
24 hours post 
LY3434172 
infusioncinfusi
onf
ECG (triplicate) 
Before blood 
draw.d
X
X
X
X
X
X
C1D4 
4
72 hours post 
LY3434172 
infusioncinfusionf
X
X
C1D8
8
168 hours post 
LY3434172 
infusioncinfusionf
X
X
X
X
X
X
X
C1D15
15
336 hours post 
LY3434172 
infusioncinfusionf
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 127
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C2D1
22
0 hour 
predosece
PK, IG, and 
biomarkers:  
collect samples 
in the morning 
of infusion day 
prior to start of 
first infusion of 
the day
X
X
X
X
X
X
X
C2D1
22
1 hour post 
LY3434172 
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
C2D1
22
3 hours post 
LY3434172 
infusionf
X
X
C2D2 
24
24 hours post 
LY3434172 
infusioncinfusionf
X
X
C2D8
30
168 hours post 
LY3434172 
infusioncinfusionf
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 128
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C3D1
43
0 hour
predosede
PK, IG, and 
biomarkers:  
collect samples 
in the morning 
of infusion day 
prior to start of 
first infusion of 
the day
X
X
X
X
X
X
XeXg
X
X
C3D1
43
1 hour 
postdose
infusionf
ECG
(triplicate).  
Before blood 
draw.d
X
X
X
C4D1
64
0 hour 
predosede
PK, IG, and 
collect samples 
in the morning 
of infusion day 
prior to start of 
first infusion of 
the day
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 129
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Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
C6D1
0 hour 
predosede
PK:  collect 
sample for all 
patients
X
X
X
C8D1; then, 
Q4C (Cycle 
12…) 
148, 
232…
0 hour 
predosede
PK:  collect PK 
sample for all 
patients 
X
X
X
When/if any 
DLT or DLT 
equivalent 
occurs
Anytime
X
X
X
Last 
LY3434172 
dose (if 
known)
0 hour 
predosede
sample
PK, IG, and 
biomarkers:  
collect sample 
2 hours prior 
to start of first 
infusion of the 
day
X
X
X
30 days post 
last 
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  
Before blood 
draw.
X
X
X
X


J1E-MC-JZEA(b) Phase 1 Oncology Protocol
Page 130
LY3434172
Pharmacokinetic, Immunogenicity, Biomarker, and ECG Collection Time Points Cohorts with Q3W Dosing (Cohort A7 and A8)
Cycle/Day
Study 
Day
Sample Time
(Relative to 
STARTthe END
of LY3434172 
Infusion)
PKa
IGa
Whole
Blood
(PGx)
Biomarker Collection
ECG
Plasma
Ex vivo
Whole
Blood & 
PBMCb
Serum
Tissue
sPD-1 and 
sPD-L1
Stoolc
60 days post 
last 
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  
Before blood 
draw.
X
X
X
X
90 days post 
last
LY3434172 
dose
Anytimec
Anytimef
ECG (single).  
Before blood 
draw.
X
X
X
Disease 
progesssion
Anytime before 
next anticancer 
treatment.
Highly 
recommended
X
X 
(optional
)
X
c    Fecal collections will begin at baseline with any new patients starting the trial at that time, and as the collection materials become available.
d
Triplicate ECGs: the 3 replicates should be approximately 1 minute apart, with all 3 replicates within a set conducted within a 5-minute timeframe.
e
Collect samples in the morning of infusion day prior to the start of first infusion of the day. 
f
The 2-, 41-, 36-, 24-, 72-, and 168- and 336-hour samples are relative to the STARTEND of the corresponding dosing event.  They must be collected after the 
completion of the infusion.  Their sampling windows are ±15 minutes (2-,1- and 43-hour), ± 4 hours (24-hour), ± 24 hours (72-, 168- and 336-hour), 
respectively.  The samples at 30, 60, and 90 days post last LY3434172 dose have sampling windows of ± 7 days.
g
Tissue biopsy sample within 3 days prior to C3D1.


L e o  D o c u m e n t  I D  =  3 3 5 6 2 0 9 6 - d b 3 4 - 4 5 b 5 - 9 8 c 0 - e 4 8 e 1 8 2 3 8 0 8 1
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  2 5 - N o v - 2 0 1 9  1 8 : 0 2 : 5 6  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 2 - D e c - 2 0 1 9  1 7 : 1 9 : 5 2  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D

SAP_001.pdf: 
J1E-MC-JZEA Statistical Analysis Plan Version 1 
 
A Phase 1 Study of LY3434172, a Bispecific Antibody Monotherapy in Advance Solid Tumors 
 
NCT03936959 
 
Approval Date: 29-Apr-2019 


J 1 E -M C - J Z E A St ati sti c al A n al y si s Pl a n V er si o n 1
P a g e 1
L Y 3 4 3 4 1 7 2
1.
St ati sti c al A n al y si s Pl a n:  J 1 E -M C -J Z E A
A P h a s e 1 St u d y  of L Y 3 43 4 1 7 2 , a Bi s p e cifi c Anti b o d y  
M o n ot h er a p y  i n A d v a n c e d S oli d T u m or s
C o nfi d e nti al I nf or m ati o n
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d t h e i nf or m ati o n c o nt ai n e d 
wit hi n it m a y n ot b e r e pr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e a p pr o v al of Eli Lill y 
a n d C o m p a n y or it s s u b si di ari e s.
N ot e t o R e g ul at or y A ut h oriti e s:
T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p e r s on al d at a 
a n d/ or c o m m er ci all y c o nfi d e nti al i nf or m ati o n e x e m pt fr o m p u bli c di s cl o s ur e. Eli Lill y a n d 
C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o a n y p u bli c r el e a s e .  I n 
t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) 
E x e m pti o n 4 a n d m a y n ot b e r e pr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n 
a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s.
L Y 3 4 3 4 1 7 2
St u d y J 1 E- M C -J Z E A i s a m ulti c e nt er, n o nr a n d o mi z e d, o p e n-l a b el, d o s e-e s c al ati o n P h a s e 1 
s t u d y of i ntr a v e n o u s L Y 3 4 3 4 1 7 2 i n p ati e nt s wit h a d v a n c e d s oli d t u m or s.
Eli Lill y a n d C o m p a n y
I n di a n a p oli s, I n di a n a U S A 4 6 2 8 5
Pr ot o c ol J 1 E -M C -J Z E A
P h a s e 1
St ati sti c al A n al y si s Pl a n el e ctr o ni c all y si g n e d a n d a p pr o v e d b y Lill y o n 
d at e pr o vi d e d b el o w.
A p pr o v al D at e: 2 9- A pr- 2 0 1 9 G M T


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2.
Table of Contents
Section
Page
1.
Statistical Analysis Plan:  J1E-MC-JZEA A Phase 1 Study of 
LY3434172, a Bispecific Antibody Monotherapy in Advanced Solid 
Tumors ...............................................................................................................................1
2.
Table of Contents................................................................................................................2
3.
Revision History .................................................................................................................6
4.
Study Objectives.................................................................................................................7
4.1.
Primary Objective ..........................................................................................................7
4.2.
Secondary Objectives.....................................................................................................7
4.3.
Tertiary/Exploratory Objectives .....................................................................................7
5.
Study Design.......................................................................................................................8
5.1.
Summary of Study Design..............................................................................................8
6.
A Priori Statistical Methods ................................................................................................9
6.1.
Sample Size Determination ............................................................................................9
6.2.
General Considerations ..................................................................................................9
6.2.1.
Populations ............................................................................................................9
6.2.2.
Definitions and Conventions ................................................................................10
6.3.
Adjustments for Covariates ..........................................................................................10
6.4.
Handling of Dropouts or Missing Data.........................................................................10
6.5.
Multicenter Studies ......................................................................................................11
6.6.
Multiple Comparisons/Multiplicity...............................................................................11
6.7.
Patient Disposition .......................................................................................................11
6.8.
Patient Characteristics ..................................................................................................11
6.8.1.
Demographics......................................................................................................11
6.8.2.
Baseline Disease Characteristics ..........................................................................11
6.8.3.
Prior Therapies.....................................................................................................11
6.8.4.
Historical Illnesses...............................................................................................12
6.9.
Treatment Compliance .................................................................................................12
6.10. Concomitant Therapy...................................................................................................12
6.11. Postdiscontinuation Therapy ........................................................................................12
6.12. Safety Analyses............................................................................................................12
6.12.1.
Extent of Exposure...............................................................................................12
6.12.2.
Dose-Limiting Toxicities and DLT-Equivalent Toxicities ....................................13
6.12.3.
Adverse Events ....................................................................................................13
6.12.4.
Deaths..................................................................................................................14
6.12.5.
Clinical Laboratory Evaluation.............................................................................14


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6.12.6.
Vital Signs and Other Physical Findings...............................................................14
6.12.7.
Electrocardiograms ..............................................................................................14
6.13. Efficacy Analyses ........................................................................................................14
6.13.1.
Tumor Measurement ............................................................................................15
6.13.2.
Objective Response Rate and Disease Control Rate..............................................15
6.13.3.
Time to Response.................................................................................................15
6.13.4.
Progression-Free Survival ....................................................................................16
6.13.5.
Duration of Response...........................................................................................17
6.13.6.
Immuno-Related Efficacy Analysis Variables ......................................................17
6.13.7.
Overall Survival...................................................................................................18
6.14. Subgroup Analyses.......................................................................................................18
6.15. Immunogenicity Analysis.............................................................................................18
6.16. Pharmacokinetic/Pharmacodynamic Analyses..............................................................19
6.17. Biomarker Analysis......................................................................................................19
6.18. Interim Analysis...........................................................................................................19
6.19. Additional Reports to Support the Clinical Trial Registry.............................................20
7.
References ........................................................................................................................22


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Table of Contents
Table
Page
Table JZEA.6.1.
Definitions and Data Handling Conventions ...........................................10
Table JZEA.6.2.
Rules for Determining Date of Progression or Censor for Progression-Free 
Survival..................................................................................................16


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Table of Contents
Figure
Page
Figure JZEA.5.1.
Illustration of study design........................................................................8


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3.
Revision History
Statistical Analysis Plan (SAP) Version 1 was approved prior to the first visit when a subject 
receives study drug or any other protocol intervention.


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4.
Study Objectives
4.1.
Primary Objective
The primary objective of this study is to assess the safety and tolerability of LY3434172, thereby 
identifying a recommended Phase 2 Dose (RP2D) to be administered to patients with advanced 
solid tumors.
4.2.
Secondary Objectives

  to assess the pharmacokinetics (PK) of LY3434172 in patients with solid tumors

  to assess the preliminary antitumor activity of LY3434172
4.3.
Tertiary/Exploratory Objectives

to characterize tumor tissue and blood biomarkers relevant to LY3434172, including but 
not limited to immune cells/immune functioning, mechanism of action of study drugs, 
cancer-related pathways, and disease state

to explore the association among biomarkers, doses, concentrations, and 
clinical outcomes

to assess the immunogenicity of LY3434172 in patients with advanced solid tumors

to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 
LY3434172 administered as monotherapy


J 1 E -M C -J Z E A St ati sti c al A n al y si s Pl a n V er si o n 1
P a g e 8
L Y 3 4 3 4 1 7 2
5.
St u d y  D e si g n
5. 1.
S u m m ar y of St u d y D e si g n
 
 
T he d ose esc alat i on will e m pl o y a mo difie d t o xi cit y pr o ba bilit y int er val 2 ( m T PI 2) m et h o d alo n g 
wi t h P K/ p har mac o d y na mic a nal ysis t o ide nt if y an R P 2 D. T he R P 2 D will be deter mi ne d base d 
o n t he n u m ber of o bser ve d d ose -li miti n g t o xicities ( D L Ts) a n d P K/p har mac o d y na mic data. T he 
R P 2 D m a y be belo w t h e m a xi m u m t olerate d d ose ( M T D), w hic h ma y n ot necessaril y be reac he d 
d uri n g t he d ose escalat i ons. 
T he D L T o bser vat i on will i ncl u de t he o bser vati o n peri o d ( C y cle 1, 4 2 da ys) for C o h ort A 1 
( C ycle 1, 2 8 da ys) ; f or C o h ort s A 2 t o A 5 ( A 2 t o A 6 if C o h ort A 6 is o pe ne d ; C ycle 1 a n d 2 ,
4 2 d a y s); a n d f or C o h orts A 7 a n d A 8.  O nce t he D L T peri o d i s c om p lete d f or res pecti ve 
C o h orts A 1 t o A 5/ 6 , u p t o a p pr o xi matel y 1 2 t o 1 5 a d dit i onal patie nts ma y be a d de d t o 2 d ose 
le vels selecte d fr om C o h or ts A 4 a n d A 5/ 6 ( Fi g ure J Z E A. 5. 1).
C CI
C
C
I
C CI
C CI


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6.
A Priori Statistical Methods
6.1.
Sample Size Determination
The sample size determination is described in Section 10.1 of Protocol JZEA.
6.2.
General Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company (Lilly) or 
its designee.
Sponsor standard tables, figures, and listings (TFLs) and supporting programs and software 
(eg, SAS®) will be utilized for all analyses where a suitable standard exists. Data derivations in 
this SAP are defined based upon current sponsor reporting standards at the time of writing, and 
may be updated at the time of analysis in order to maintain accordance with the most current 
sponsor standards at that time.
Unless otherwise noted, summaries of continuous variables will include a mean, median, 
standard deviation, minimum, and maximum.  When appropriate, lower and upper quartiles will 
also be presented.
Unless otherwise noted, summaries of categorical variables will include the frequency and 
percentage (relative to the population being analyzed) of each category.
Unless otherwise stated, data will be summarized by dose escalation cohorts that will indicate the 
assigned treatment regimen and dose schedule for LY3434172.
In addition, safety data may be summarized by the same treatment regimen and dose schedule, 
and efficacy data may be summarized by the same indication and treatment regimen.
Additional exploratory analyses of the data will be conducted as deemed appropriate.
6.2.1. Populations
The following population will be defined for this study:
Entered population:  will include all patients who sign the informed consent document.
Enrolled/safety population:  will include all patients who received any quantity of study 
treatment (LY3434172), regardless of their eligibility for the study.  The safety and efficacy 
evaluation will be performed based on the first dose of study treatment a patient actually 
received.  This population will be used for all dosing/exposure, safety, and efficacy analyses.
Dose-limiting toxicity–evaluable population:  will include all patients from the study who have 
completed the DLT observation period (Cycle 1) or discontinued treatment before the end of the 
DLT observation period but with a documented DLT assessment. Exposure and safety 
summaries may be repeated for this population.
Pharmacokinetic population:  will include all enrolled patients from whom a valid assay result 
(according to laboratory guidelines) has been obtained.


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Biomarker population:  will include the subset of enrolled patients from whom a valid assay 
result has been obtained.  No imputation will be performed for missing data due to the limitation 
of small sample size.
6.2.2. Definitions and Conventions
The following definitions and data handling conventions will be used in the analysis.
Table JZEA.6.1.
Definitions and Data Handling Conventions
Term
Definition or Rule
Relative Study Day
If assessment is on or after date of first dose, then
(date of assessment) – (date of first study drug dose) +1
If assessment precedes first dose of drug, then
(date of assessment) – (date of first study drug dose)
There is no Study Day 0. Study Day 1 is the date of first dose and Study Day -1 is the day 
before the first dose.
Cycle Day
If assessment is on or after date of first dose in cycle, then
(date of assessment) – (date of first study drug dose in cycle) +1
There is no Cycle Day 0. Cycle Day 1 is the date of first dose in that cycle.
Baseline
For change from baseline analyses, baseline value is defined as the last reported measure on 
or before the first dose date (prior to the dose administration), unless otherwise specified.
Age (years)
Age is based on date of birth and informed consent date.  If only a year and month are 
provided in the date of birth, set day to 15.  If only a year is provided, set day to 1 and month 
to 7 (July).
Duration
Duration (days): (End Date – Start Date + 1)
Duration (weeks):
(End Date – Start Date + 1)/7
Duration (months):
(End Date – Start Date + 1)/30.4375 (Days in months = 
(1/12)*average number of days in a year)
Duration (years): (End Date – Start Date + 1)/365.25 (Average days in a year = 365.25, 
reflecting the Julian Year of 3 years with 365 days each and 1 leap year of 366 days)
Time-to-Event
The event or censoring time (days) is calculated as:
Date of event/censoring Date of first dose of study drug + 1
6.3.
Adjustments for Covariates
Given the small sample size for each tumor type and treatment, no formal analysis investigating 
the impact of covariates is planned.  If data warrant, exploratory analyses may incorporate 
patient disease characteristics in evaluation of efficacy parameters.
6.4.
Handling of Dropouts or Missing Data
Missing data, except for dates, will not be imputed. They will be kept as missing in the data 
analyses, except for dates when used in calculations of relative study day, for which sponsor 
reporting standards will be utilized for imputation rules, defined as: Missing start days will be 
replaced with 1 and missing day/month with 01 JAN. Missing end days will be replaced with the 
last day of the month, and missing day/month with 31 DEC. The imputation rule may be 
updated at the time of study reporting if necessary to maintain accordance with most recent 
sponsor standards. Partial dates should be reported in all listings and not the imputed date.


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For time-to-event endpoints, the method for handling missing data will be censoring. Additional 
sensitivity analyses may be conducted applying different censoring rules if data warrant and will 
follow sponsor-defined standards.
6.5.
Multicenter Studies
Given the small number of patients for each tumor type and treatment, patients across all sites
will be grouped together for analysis purposes.
6.6.
Multiple Comparisons/Multiplicity
No formal hypothesis testing is planned for this study; thus, there will be no adjustments 
for multiplicity.
6.7.
Patient Disposition
Patient disposition will be summarized and listed for all patients entered into the study.  It will
include a summary of the number and percentage of patients entered into the study, enrolled in 
the study, and treated as well as number and percentage of patients completing the study, or 
discontinuing (overall and by reason for discontinuation of study drug).  All patient 
discontinuation data collected on the case report form will be listed.
Important protocol deviations that potentially compromise the data integrity and patients’ safety 
will be summarized for the safety population.  These deviations will include those that can be 
identified programmatically and those that can only be identified by the clinical research 
associate during monitoring.  Important protocol deviations are described in a separate
document within the study Trial Master File.
6.8.
Patient Characteristics
Patient characteristics will be summarized and listed for the safety population.  Details of the 
patient characteristics are described in the following sections.  Other patient characteristics will 
be summarized as deemed appropriate.
6.8.1. Demographics
Patient demographics will include sex, race, ethnicity, country, age, age group (<65 years; 
≥65 years; <70 years; ≥70 years), height, weight, and body mass index.
6.8.2. Baseline Disease Characteristics
Baseline disease characteristics will include Eastern Cooperative Oncology Group (ECOG) 
performance status (PS), initial pathological diagnosis, basis for initial diagnosis, disease stage, 
histopathological grade, tobacco usage (never, current, former), and alcohol use.
6.8.3. Prior Therapies
Prior radiotherapy, surgery, and systemic therapy will be summarized.  Prior radiotherapy will be 
categorized by reason for the regimen (neoadjuvant, adjuvant, neoadjuvant plus adjuvant, 
advanced/metastatic), and prior surgery will be categorized by intent (curative, palliative).  Prior 


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systemic therapies will be categorized by setting (neoadjuvant, adjuvant, locally advanced, 
metastatic).  Frequency of each specific therapy will be tabulated within each type of regimen 
and reason for regimen.  
Patients who received any prior anti‒programmed death 1 (PD-1) and/or anti‒programmed death 
ligand 1 (PD-L1) therapies will be summarized and listed.
6.8.4. Historical Illnesses
Historical illnesses are events in the past that ended before the date on which the informed 
consent form was signed.  Historical illnesses (coded according to the Medical Dictionary for 
Regulatory Activities [MedDRA]) will be listed for all enrolled patients.  
6.9.
Treatment Compliance
LY3434172 will be administered intravenously at the investigational sites only. As a result, 
patient compliance will be ensured. Any cases deemed as not compliant will be reported as 
protocol deviations.
6.10. Concomitant Therapy
Concomitant medications will be summarized and listed for the safety population.
For corticosteroids and/or immunosuppressives, the indication, administration route, individual 
dose, duration, dose adjustment, and reason for use will be summarized and listed.
6.11. Postdiscontinuation Therapy
The numbers and percentages of patients reporting postdiscontinuation therapies will be 
provided overall, by type of therapy (surgery, radiotherapy, or systemic therapy), and by 
drug name.
6.12. Safety Analyses
All patients who receive any quantity of LY3434172 will be evaluated for safety and toxicity.  
Details of the analyses are described in the following subsections.
6.12.1. Extent of Exposure
A summary of exposure will be provided for study drug, including cycle received, cumulative 
dose, and duration of therapy.  Duration of therapy is defined as Discontinuation date – Date of 
first dose + 1.
A summary of dose intensity will be provided for study drug. Dose intensity expressed 
in mg/week will be calculated as the actual cumulative amount of drug taken divided by 
the duration of exposure in weeks.  Duration of exposure in weeks is defined as (Date of last 
dose – Date of first dose + 14)/7 for every 2 weeks (Q2W) dose, and (Date of last dose – Date of 
first dose + 21)/7 for every 3 weeks (Q3W) dose.


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Relative dose intensity will be calculated as:
100% (actual cumulative dose taken [mg] / planned cumulative dose [mg])
Note that planned dose is the same as actual dose if there is no dose modification or cycle delay.
A summary of dose adjustments will be provided for study drug, including dose omissions, dose 
reductions, dose increases, dose delays, treatment interrupted, and the corresponding reasons for 
dose adjustments for each cohort.  
6.12.2. Dose-Limiting Toxicities and DLT-Equivalent Toxicities
Definitions of DLTs and DLT-equivalent toxicities (DETs) are provided in Section 7.2.2.2 
of Protocol JZEA.
Dose-limiting toxicities will be summarized and listed for the DLT-evaluable population
(defined in Section 7.6.1 of Protocol JZEA), and DETs will be listed and summarized for the 
safety population.
6.12.3. Adverse Events
A listing of all adverse events (AEs) by patient will be presented. This listing will include 
patient number, AE (reported term and preferred perm [PT]), event start and end dates, Common 
Terminology Criteria for Adverse Events (CTCAE) grade, relationship to study drug/procedure, 
seriousness, and outcome. A listing of serious adverse events (SAEs) will be produced using a
similar format.
An overall summary will be provided for AEs. The summary will provide counts for all AEs and 
AEs related to study treatment.  Specifically, the number and percent of evaluable patients will 
be summarized by treatment for each category below:

patients with at least one treatment-emergent adverse event (TEAE)

patients with at least one Grade 3 or higher TEAE

patients with at least one SAE

patients who discontinued due to AE

patients who discontinued due to SAE

patients who died due to AE on study treatment

patients who died due to AE within 30 days of discontinuation from study treatment 
The following summaries will also be produced:

summary of all preexisting conditions

summary of TEAEs by PT (any grade and Grade ≥3)

summary of TEAEs by system organ class (SOC) and PT (any grade and Grade ≥3)

summary of TEAEs by SOC and PT and maximum grade (1-5)


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
summary of treatment-emergent SAEs by SOC and PT (any grade and Grade ≥3)

summary of AEs as reason for study treatment discontinuation by SOC and PT

summary of TEAEs leading to dose omissions, reductions, and hospitalization
In addition, immune-related adverse events (irAEs) may be summarized.  A list of what is 
considered an irAE will be defined in a separate document.
6.12.4. Deaths
All deaths recorded in this study will be included as part of the complete AE listing, where 
appropriate, and listed separately.  A summary of deaths may be presented for all patients on 
therapy if the number of events is sufficient for this to be deemed useful.
6.12.5. Clinical Laboratory Evaluation
All laboratory results will be reviewed using Spotfire® to assess changes over time and 
differences between cohort/dose levels.  Key findings will be summarized in tables and/or 
illustrated graphically using line plots over time or box plots, for example.  
Any abnormal results of clinical laboratory tests will be listed for all patients on therapy and,
where appropriate, the calculated CTCAE grades using CTCAE version 4.0 (or higher) will be 
given.  Calculated CTCAE grades will also be summarized by cohort/dose level for laboratory 
parameters where CTCAE grades are available.  A shift table of baseline grade by maximum 
postbaseline grade will be produced.
6.12.6. Vital Signs and Other Physical Findings
All vital sign results will be reviewed using Spotfire to assess changes over time and differences 
between cohorts/dose levels.  Key findings will be summarized in tables and/or illustrated 
graphically using line plots over time or box plots, for example.
Any significant physical examination findings and results will be listed.
6.12.7. Electrocardiograms
Any abnormal electrocardiogram data based on local testing will be listed and summarized for 
the safety population.  Further exploratory analyses may be conducted as warranted.
6.13. Efficacy Analyses
All efficacy analyses will be performed on the safety population.  This study is not designed to 
perform hypothesis testing on efficacy; however, all efficacy data will be listed and summarized.
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009)
will be applied as the primary criteria for assessment of tumor response.  Local tumor imaging 
(investigator assessment with site radiological reading) will be used.  
Two sets of analyses will be provided, with 1 set based on RECIST version 1.1 and the other set 
based on RECIST version 1.1 with confirmatory scan for disease progression.  The notation “ir” 


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(immune-related) will be used to denote the analyses based on RECIST version 1.1 with 
confirmatory scan for disease progression; it does not indicate that any of the assessments based 
on irRECIST, irRC, or iRECIST will be used in the study or analyses.
6.13.1. Tumor Measurement
Tumor size is the sum of the uni-dimensional measurements for each lesion. Change in tumor 
size is defined as the percent change in tumor size from the baseline evaluation to the postdose 
evaluation at each assessment. 
Individual changes in the tumor size over time will be presented graphically by waterfall and 
spider plots within a tumor type.  
6.13.2. Objective Response Rate and Disease Control Rate
Objective response rate (ORR) and disease control rate (DCR) are summary measures of best 
overall response (BOR) as defined by RECIST version 1.1.  Best overall response is derived 
from time point responses.  All time point responses observed while on study treatment and 
during the short-term follow-up period will be included in the derivation.  Patients’ responses 
after objective progression or start of new anticancer therapy are excluded from the 
determination of best response.  Best overall response of complete response (CR) and partial 
response (PR) should be confirmed by repeated assessment at least 4 weeks following the 
initial observation.  Each patient’s BOR will be categorized as CR, PR, stable disease (SD), 
partial disease (PD), or not evaluable (NE).  If appropriate, the best overall tumor response 
may be calculated by Lilly using all available lesion measurement data to confirm the 
investigator assessments.  
Objective response rate will be estimated by dividing the total number of confirmed responders 
(CR+PR) by the number of enrolled patients who have received any quantity of study treatment.
Patients who do not have any postbaseline tumor response assessments for any reason are
considered NE and will be included in the denominator when calculating the response rate.
Disease control rate is defined as the number of patients with SD, confirmed PR, or confirmed 
CR (CR+PR+SD) divided by the number of enrolled patients who have received any quantity of 
study treatment.
The estimates of ORR and DCR along with exact 95% confidence interval (CI) will be reported. 
6.13.3. Time to Response
Time to response (TTR) is the time from the date of first study treatment until the first evidence 
of a confirmed CR or PR.  If a patient did not experience a confirmed CR or PR, the TTR will be 
censored at the treatment starting date.
Time to response will be estimated using the Kaplan-Meier (KM) method (Kaplan and 
Meier 1958) and summary statistics including median and 95% CI will be presented.  


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6.13.4. Progression-Free Survival
Progression-free survival is defined as the time from the date of first dose until the date of the 
first observed radiographic documentation of progression or death due to any cause, whichever 
is earlier.  
Table JZEA.6.2 lists rules for determining date of progression or censor for PFS.  
Table JZEA.6.2.
Rules for Determining Date of Progression or Censor for 
Progression-Free Survival
Abbreviation:  PD = partial disease.
Note: 1) If there are multiple dates associated with 1 radiological tumor assessment, the 
assessment date will be set to the first date when the overall response is PD and the last date 
otherwise; 2) Symptomatic deteriorations (ie, symptomatic progressions, which are not 
radiologically confirmed) will not be considered as progressions; and 3) A radiological tumor 
assessment is considered adequate if its response is among CR, PR, SD, or PD.
Progression-free survival will be estimated using the KM method.  Median PFS and 95% CI as 
well as PFS rates (and 95% CI) at 12, 18, and 24 weeks will be presented. 
Situation
Event/Censor
Date of Event or Censor
Tumor progression or death
Event
Earliest date of PD or death
No tumor progression and no death
Censored
Date of last adequate radiological 
assessment or date of first dose
(whichever is later)
unless
No baseline radiological tumor assessment 
available
Censored
Date of first dose
No adequate postbaseline radiological 
tumor assessment available
and death reported after 2 consecutively 
missed tumor assessment intervals
following enrollment 
Censored
Date of first dose
New anticancer treatment started
Censored
Date of adequate radiological
assessment prior to start of new 
therapy or date of first dose 
(whichever is later)
Tumor progression or death
documented immediately after 2 or more 
consecutively missed tumor assessment 
intervals following last adequate radiological 
tumor assessment or enrollment (whichever 
is later)
Censored
Date of last adequate radiological 
assessment or date of first dose 
(whichever is later)


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6.13.5. Duration of Response
The duration of response (DoR) time is defined only for responders (patients with a confirmed 
CR or PR).  It is measured from the date of first evidence of CR or PR to the date of the first 
observed radiographically documented PD or the date of death due to any cause, whichever is 
earlier.  For clarity, the start date should be determined by the initial assessment of CR or PR, 
not the date of confirmation of CR or PR.  Start date is calculated as date of progression or 
death – date of first response evaluation of CR or PR + 1.
Duration of response will be censored according to the same rules as PFS, with the addition of 
the following rule:  if a patient begins postdiscontinuation therapy, DoR will be censored on the 
day of the last response evaluation prior to the initiation of postdiscontinuation therapy.
Duration of response will be estimated using the KM method and summary statistics including 
median and 95% CI will be presented.  
6.13.6. Immuno-Related Efficacy Analysis Variables
Study JZEA will use RECIST version 1.1 with confirmatory scan for disease progression.  
Detailed application of RECIST version 1.1 with confirmatory scan for PD can be found in 
Section 9.1.1.2 of Protocol JZEA.  
Immune-related objective response rate (irORR) is defined as the proportion of treated 
patients achieving a BOR of CR or PR per RECIST version 1.1 with confirmatory scan for PD—
particularly, the BOR by RECIST version 1.1 with confirmatory scan for PD closely related to 
confirmed response by RECIST. Immune-related objective response rate further captures 
responses after unconfirmed PD and does not require confirmation.  For example:

If the best response by RECIST version 1.1 is CR, then the best response by RECIST 
version 1.1 with confirmatory scan for PD is CR.

If the best response by RECIST version 1.1 is PR, SD, or PD, the best response by 
RECIST version 1.1 with confirmatory scan for PD is the best response over the initial 
assessment (prior to PD by RECIST) and the confirmation stage.
Overall, the best response by RECIST version 1.1 with confirmatory scan for PD should be the 
same or better than the best response by RECIST criteria.  In addition, patients who do not have 
any postbaseline tumor response assessments for any reason are considered NE and will be 
included in the denominator when calculating the response rate.
Immune-related disease control rate (irDCR) is defined as the number of patients with 
immune-related stable disease (irSD), immune-related complete response (irCR), or immune-
related partial response (irPR) divided by the number of enrolled patients who have received any 
quantity of study treatment.
Immune-related time to response (irTTR) is the time from the date of first study treatment 
until the first documented irCR or irPR.  


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Immune-related PFS (irPFS):  The date from the treatment start date to the time of PD assessed 
by RECIST version 1.1 with confirmatory scan for PD.

If the initial PD is confirmed, then the date of immune-related partial disease (irPD) is the 
initial PD date by RECIST version 1.1.

If the initial PD is unconfirmed, then the date of irPD is the date of second PD.
Immune-related duration of response (irDoR):  The irDoR is defined from the date of first 
documented irCR or irPR (responder) to the date of irPD or the date of death due to any cause, 
whichever is earlier. 
In addition, the best response after initial PD may be listed.  Other efficacy analysis based on 
irRECIST may be performed for exploratory analysis.
6.13.7. Overall Survival
Overall survival is defined as the time from first study treatment until death due to any cause.  If 
the patient is not known to have died at the data inclusion cutoff date for the analysis (or is lost to 
follow-up), OS data will be censored on the last date on which the patient was known to be alive.
Overall survival will be estimated using the KM method.  Median OS along with 95% CI as well 
as OS rates (and 95% CI) at 1 and 2 years will presented. 
6.14. Subgroup Analyses
Subgroup analyses of efficacy endpoints may be performed for each of the potential prognostic 
subgroup variables listed below.  

sex (male; female)

age (<65 years; ≥65 years; <70 years; ≥70 years)

baseline ECOG PS (0; 1)

ethnicity (White; East Asian; others)

smoking status (never; current; former)

prior lines of therapy (such as first line, second line, third line, and beyond)
Other subgroups may be added as deemed necessary.
6.15. Immunogenicity Analysis
Immunogenicity (anti-LY3434172 antibody) incidence will be tabulated, and correlation to 
drug level, activity, PK parameters, and safety will be assessed, respectively, as appropriate.  
The measures that will be analyzed include baseline presence and level of anti-drug 
antibodies (ADAs), treatment-emergent ADAs (defined in Section 10.3.3.7 of Protocol JZEA), 
levels of neutralizing ADA, and incidence and levels of ADA associated with infusion-related 
reactions.


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6.16. Pharmacokinetic/Pharmacodynamic Analyses
Selected PK descriptors (based on actual sampling times), including approximate maximum 
observed drug concentration (Cmax) and area under the concentration versus time curve 
(AUC), will be calculated by noncompartmental analysis methods. As an exploratory analysis, 
PK descriptor estimates for trough concentrations (minimum observed drug concentration 
[Cmin]) at steady state following repeated dose may be evaluated.
In addition, PK parameter estimates for LY3434172 may be calculated by population PK
analysis methods using nonlinear mixed effects modeling (NONMEM). The version of any
software used for the analysis will be documented, and the program will meet the Lilly
requirements for software validation. It is possible that other validated, equivalent PK 
software programs may be used if appropriate, warranted, and approved by Global 
PK/pharmacodynamic management.
Following review of the biomarker analyses (see Section 6.17), pharmacodynamic biomarker 
analysis with tumor type, changes in biomarker levels over time, and association to dose levels 
or exposure may be explored if applicable. Pharmacokinetic/pharmacodynamic analyses may be 
conducted to explore exposure-response relationships between LY3434172 concentrations in 
systemic circulation and relevant pharmacodynamic measures such as soluble PD-1, soluble 
PD-L1, and interleukin 2 (IL-2) stimulation. Either summary metrics of exposure and effect (for
example, individual trough concentrations) or concentration time profiles of exposure and effect
could be used for these analyses.
6.17. Biomarker Analysis
Association analysis between selected biomarkers and clinical outcome may be assessed if 
applicable. If the ORR is ≥10%, the baseline biomarkers that potentially predict better response 
to LY3434172 may be explored using a single- or multimarker approach. In addition (as 
discussed in Section 6.16), pharmacodynamic/biomarker analyses related to treatment, immune 
functioning, mechanism of action of study drugs, and/or cancer may be explored if applicable. 
Biomarker variations over tumor types, the on-treatment percentage changes in selected 
biomarker(s) from baseline, and potential correlation between biomarker(s) and different 
LY3434172 dose levels (or exposure) may be explored if applicable.
6.18. Interim Analysis
In this Phase 1 dose-finding study, safety, PK, and biomarker data (if available) will be reviewed 
on a cohort-by-cohort basis during the study until the MTD and/or RP2D is determined.  The 
purpose of these cohort-by-cohort data reviews is to evaluate the safety data at each dose level 
and determine if a DLT has been observed.  The decision whether to advance to the next dose 
level will be made following discussion between the investigators and Lilly and will be 
communicated to the sites prior to patients being treated in the subsequent cohort.
Safety and available PK data will be reviewed during the study to inform dose escalation,
modifications to the dose-escalation strategy, or other design elements.


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After all patients in Cohorts 1 to A5/6 have completed the DLT evaluation period or 
discontinuous treatment, an interim safety and PK/pharmacodynamic analysis will be conducted.  
In this interim analysis, early antitumor activity may also be explored.  Additional enrollment of 
patients to Cohorts A4 to A5/6 can continue during the interim analysis.
Interim analysis may also be combined with any prespecified safety review or reporting (ie, Trial 
Level Safety Reviews, Development Safety Update Reviews, or Investigator’s Brochure
update reviews).
The final overall analysis of Study JZEA will be conducted with the safety and efficacy primary 
analysis approximately 52 weeks (12 months) after the last enters/starts study treatment.  If it is 
deemed that enough data have been obtained to assess the primary and secondary objectives, a 
clinical study report may be created before the last patient visit.  In this case, all data collected 
before the data cutoff date will be used for the analysis of safety, efficacy, PK, and 
pharmacodynamic biomarkers.  All data defined in the protocol will continue to be collected 
from patients on treatment after data-cutoff date and results will be listed.  However, summary 
tables including data collected after the data-cutoff date will not be created.
6.19. Additional Reports to Support the Clinical Trial Registry
Additional analyses will be performed for the purpose of fulfilling the Clinical Trial Registry 
(CTR) requirements.
Analyses provided for the CTR requirements include the following:

Summary of AEs, provided as a dataset that will be converted to an XML file.  Both 
SAEs and “Other” AEs are summarized by treatment group and by MedDRA PT.

An AE is considered “Serious” whether or not it is a TEAE.

An AE is considered in the “Other” category if it is both a TEAE and is not serious.

For each SAE and “Other” AE, for each term and treatment group, the following 
are provided:
o
the number of participants at risk of an event (if certain subjects cannot be at risk 
for some reason, for example, gender-specific AEs, then the study team must 
adjust the number to only include the patients at risk)
o
the number of participants who experienced each event term
o
the number of events experienced

Consistent with www.ClinicalTrials.gov requirements, a threshold for frequency of 
“Other” AEs can be implemented rather than presenting all “Other” AEs.  For example, 
“Other” AEs that occur in <5% of patients in any treatment group may not be included if 
a 5% threshold is chosen.  The frequency threshold must be less than or equal to the 
allowed maximum of 5%.


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A participant flow will be created that will describe how many patients completed the study, and 
for those who did not, the frequency of each reason for not completing.  This analysis will be 
based on study discontinuation, not treatment discontinuation.  A patient will be identified as 
having completed the study on the study discontinuation electronic case report form, if available, 
or if information for both primary and secondary endpoints has been observed.


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7.
References
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, 
Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. 
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45(2):228-247.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc.
1958;53(282):457-481.


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