A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Phase: PHASE1
Conditions: Pharmacokinetics, Solid Tumor, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title:
NCT number:
Document Date:
NCT03396445
A Phase 1 Study of MK 5890 as 
Monotherapy and in Combination with 
Pembrolizumab in Participants with 
Advanced Solid Tumors
04-Aug-2022

Product:  MK-5890 
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Title Page
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME LLC, RAHWAY, NJ, USA (MSD).
Protocol Title: A Phase 1 Study of MK-5890 as Monotherapy and in Combination with 
Pembrolizumab in Participants with Advanced Solid Tumors
Protocol Number: 001-06
Compound Number: MK-5890
Sponsor Name and Legal Registered Address: 
Merck Sharp & Dohme LLC
(hereafter referred to as the Sponsor or MSD)
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Regulatory Agency Identifying Number(s):
IND NUMBER: 136304
EudraCT NUMBER: 2017-004550-41
Approval Date:  04 August 2022
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Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor Contact information can be found in the Investigator Trial 
File Binder (or equivalent). 
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 6
04-AUG-2022
Merck Sharp and & Dohme Corp. underwent an entity name and address change 
to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted 
only in an entity name change and update to the address. 
Amendment 5
27-OCT-2021
To update the frequency of hematology and chemistry panel sample collection in 
participants with TNBC treated in Arm 4.
Amendment 4
15-JUL-2021
To update the dose modification and toxicity management guidelines for irAEs.
Amendment 3
25-JAN-2021
Cohort expansion to evaluate the efficacy and safety of MK-5890 in combination 
with pembrolizumab and nab-paclitaxel for the treatment of participants with 
locally recurrent inoperable TNBC cancer not previously treated with 
chemotherapy and which cannot be treated with curative intent or with 
previously not treated metastatic TNBC whose tumor PD-L1 CPS is less than 10. 
Amendment 2
01-JUL 2019
Based on a review of currently available preclinical and clinical data, several 
expansion cohorts were added to further examine safety and exploratory efficacy 
of MK-5890 when used as monotherapy and in combination with 
pembrolizumab in select tumor types. Furthermore, an additional cohort of 
participants with nonsquamous NSCLC was added to assess the safety and 
tolerability of MK-5890 in combination with pembrolizumab and standard 
chemotherapy.
Amendment 1
09-MAR-2018
The protocol was amended to clarify eligibility of participants; infusion time for 
MK-5890; noncompliance due to drug-related AE(s); and the assessment and 
management of potential infusion reactions to MK-5890.
Original Protocol 
23-OCT-2017
Not applicable.
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment 06
Overall Rationale for the Amendment:
Sponsor underwent an entity and name change and update to the address. 
Summary of Changes Table:
Section # and Name
Description of 
Change
Brief Rationale
Title Page 
12.1 Appendix 1: Study 
Governance Considerations, 
Code of Conduct for Clinical 
Trials
Throughout
Sponsor entity 
name and address 
change. 
Merck Sharp & Dohme Corp. underwent an entity name and address change 
to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted 
only in an entity change and update to address. 
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................4
1.
Synopsis.......................................................................................................................15
2.
Schedule of Activities (SoA)......................................................................................19
2.1
Schedule of Activities for the Screening & Treatment Periods - Dose 
Escalation and Confirmation Phase (Arms 1 and 2).............................................19
2.2
Schedule of Activities for the Screening & Treatment Periods – Dose 
Escalation and Confirmation Phase (Arm 3: 30 mg MK-5890 + 
200 mg Pembrolizumab + 500 mg/m2 Pemetrexed + 
AUC 5 mg/mL/min Carboplatin, all Q3W in Participants With 
Nonsquamous NSCLC)...........................................................................................23
2.3
Schedule of Activities for the Screening & Treatment Periods - Dose 
Expansion Phase (Arm 1a: 30 mg MK-5890 Q3W as Monotherapy in 
Participants With Endometrial Cancer)...............................................................27
2.4
Schedule of Activities for the Screening & Treatment Periods - Dose 
Expansion Phase (Arm 2a: 30 mg MK-5890 + 200 mg 
Pembrolizumab, Both Q3W in Participants With TNBC AND 
Arm 2b: 30 mg MK-5890 + 200 mg Pembrolizumab, Both Q3W in 
Participants With Endometrial Cancer)...............................................................31
2.5
Schedule of Activities for the Screening & Treatment Periods - Dose 
Expansion Phase (Arm 2c: 30 mg MK-5890 + 400 mg Pembrolizumab, 
Both Q6W in Participants With Endometrial Cancer) .......................................35
2.6
Schedule of Activities for the Screening & Treatment Periods - Cohort 
Expansion Phase (Arm 4: MK-5890 + Pembrolizumab, Both Q6W, 
Plus nab-Paclitaxel in Participants With Locally Recurrent 
Inoperable TNBC not Previously Treated With Chemotherapy and 
Which Cannot be Treated With Curative Intent or With not 
Previously Treated Metastatic TNBC Whose Tumor PD-L1 CPS is 
Less Than 10)...........................................................................................................40
2.7
Schedule of Activities for the End of Treatment and Post-Treatment 
Follow-Up Periods – Dose Escalation and Confirmation Phase and 
Dose Expansion Phase ............................................................................................49
2.8
Schedule of Activities for the Cross-Over Treatment Phase – Dose 
Escalation and Confirmation Phase (Arm 1) and Dose Expansion 
Phase (Arm 1a)........................................................................................................51
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3.
Introduction................................................................................................................55
3.1
Study Rationale .......................................................................................................55
3.2
Background..............................................................................................................55
3.2.1
Pharmaceutical and Therapeutic Background .....................................................55
3.2.1.1
MK-5890 Background ..................................................................................55
3.2.1.2
Pembrolizumab (MK-3475) Background .....................................................57
3.2.2
Pre-Clinical and Clinical Studies.........................................................................57
3.2.2.1
MK-5890 Pre-Clinical and Clinical Studies .................................................57
3.2.2.2
Pembrolizumab (MK-3475) Pre-Clinical and Clinical Studies ....................57
3.2.3
Ongoing Clinical Studies .....................................................................................58
3.2.3.1
MK-5890 Ongoing Clinical Studies .............................................................58
3.2.3.2
Pembrolizumab Ongoing Clinical Studies....................................................58
3.2.4
Information on Other Study-Related Therapy .....................................................58
3.3
Benefit/Risk Assessment.........................................................................................58
4.
Objectives/Hypotheses and Endpoints.....................................................................58
5.
Study Design...............................................................................................................61
5.1
Overall Design .........................................................................................................61
5.1.1
Study Diagram .....................................................................................................65
5.2
Number of Participants ..........................................................................................66
5.3
Beginning and End of Study Definition ................................................................67
5.3.1
Clinical Criteria for Early Study Termination .....................................................67
5.4
Scientific Rationale for Study Design....................................................................67
5.4.1
Rationale for Endpoints .......................................................................................69
5.4.1.1
Efficacy Endpoints........................................................................................69
5.4.1.2
Safety Endpoints...........................................................................................69
5.4.1.3
70
5.4.1.4
70
5.4.1.5
70
5.4.1.6
.70
5.4.1.6.1
71
5.4.1.6.2
71
5.4.1.6.3
71
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5.4.1.6.4
71
5.4.1.6.5
72
5.4.1.6.6
72
5.4.2
Rationale for The Use of Comparator/Placebo....................................................72
5.5
Justification for Dose ..............................................................................................72
5.5.1
72
5.5.2
.76
5.5.3
76
5.5.3.1
.76
5.5.3.2
Pembrolizumab (MK-3475)..........................................................................77
5.5.4
Rationale for Pemetrexed and Carboplatin Doses in NSCLC .............................77
5.5.5
Rationale for Nab-paclitaxel Doses in Previously Untreated Metastatic 
TNBC...................................................................................................................77
5.5.6
Dose Finding Using a Modified Toxicity Probability Interval Design................78
5.5.7
.81
6.
Study Population........................................................................................................83
6.1
Inclusion Criteria....................................................................................................83
6.2
Exclusion Criteria ...................................................................................................87
6.3
Lifestyle Restrictions...............................................................................................90
6.3.1
Meals and Dietary Restrictions............................................................................90
6.3.2
Caffeine, Alcohol, and Tobacco Restrictions ......................................................90
6.3.3
Activity ................................................................................................................90
6.4
Screen Failures ........................................................................................................91
6.5
Participant Replacement Strategy.........................................................................91
7.
Treatments..................................................................................................................91
7.1
Treatments Administered.......................................................................................91
7.2
Dose Modification (Escalation/Titration/Other)..................................................93
7.2.1
Dose Administration/Escalation ..........................................................................93
7.2.1.1
93
7.2.2
Definition of Dose-limiting Toxicity...................................................................94
7.2.3
Cross-Over Treatment Phase (Optional)..............................................................95
7.2.4
Timing of Dose Administration...........................................................................96
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7.2.5
Immune-Related Events and Dose Modification (Withhold, Treat, 
Discontinue).........................................................................................................97
7.2.5.1
Dose Modification and Toxicity Management for Adverse Events 
Associated With MK-5890 and/or Pembrolizumab......................................97
7.2.5.2
Dose Modification and Toxicity Management for Immune-Related 
AEs Associated With Pembrolizumab........................................................100
7.2.5.3
Toxicity Management of Infusion Reactions Related to 
Pembrolizumab and MK-5890....................................................................104
7.2.5.4
Dose Modification for Chemotherapy ........................................................106
7.2.5.5
Management Guidelines for Overlapping Toxicities..................................107
7.3
Method of Treatment Assignment.......................................................................108
7.3.1
Stratification.......................................................................................................109
7.4
Blinding..................................................................................................................109
7.5
Preparation/Handling/Storage/Accountability ..................................................109
7.5.1
Dose Preparation................................................................................................109
7.5.2
Handling, Storage and Accountability...............................................................109
7.6
Treatment Compliance.........................................................................................110
7.7
Concomitant Therapy...........................................................................................110
7.7.1
Acceptable Concomitant Medication.................................................................110
7.7.2
Prohibited Concomitant Medications.................................................................110
7.7.3
Rescue Medications and Supportive Care .........................................................111
7.7.3.1
Antiemetic Use............................................................................................112
7.7.3.2
Colony-Stimulating Factors........................................................................112
7.7.3.3
Pemetrexed Premedication..........................................................................112
7.7.3.4
Nab-paclitaxel Premedication.....................................................................112
7.8
Treatment After the End of the Study ................................................................112
7.9
Clinical Supplies Disclosure.................................................................................112
8.
Discontinuation/Withdrawal Criteria....................................................................113
8.1
Discontinuation of Study Treatment...................................................................113
8.2
Withdrawal from the Study .................................................................................114
8.3
Lost to Follow Up..................................................................................................115
9.
Study Assessments and Procedures........................................................................115
9.1
Administrative and General Procedures ............................................................116
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9.1.1
Informed Consent...............................................................................................116
9.1.1.1
General Informed Consent..........................................................................116
9.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research......................................................................................................116
9.1.2
Inclusion/Exclusion Criteria ..............................................................................117
9.1.3
Participant Identification Card...........................................................................117
9.1.4
Medical History .................................................................................................117
9.1.5
Prior and Concomitant Medications Review .....................................................117
9.1.5.1
Prior Medications........................................................................................117
9.1.5.2
Concomitant Medications...........................................................................117
9.1.6
Assignment of Screening Number.....................................................................118
9.1.7
Assignment of Treatment/Randomization Number...........................................118
9.1.8
Treatment Administration..................................................................................118
9.1.8.1
Timing of Dose Administration..................................................................118
9.1.9
Discontinuation and Withdrawal .......................................................................119
9.1.9.1
Withdrawal From Future Biomedical Research .........................................119
9.1.10 Participant Blinding/Unblinding........................................................................119
9.1.11 Calibration of Critical Equipment......................................................................119
9.2
Efficacy Assessments.............................................................................................120
9.2.1
Tumor Imaging and Assessment of Disease......................................................120
9.2.1.1
Initial Tumor Imaging.................................................................................120
9.2.1.2
Tumor Imaging During the Study...............................................................120
9.2.1.3
End of Treatment and Follow-Up Tumor Imaging.....................................121
9.2.1.4
RECIST 1.1 Assessment of Disease...........................................................121
9.2.1.5
iRECIST 1.1 Assessment of Disease..........................................................121
9.2.2
Eastern Cooperative Oncology Group (ECOG) Performance Scale .................124
9.3
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Reportable Safety Events .....................................................................................124
9.3.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ................................................................125
9.3.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events............126
9.3.3
Follow-up of AE, SAE, and Other Reportable Safety Event 
Information ........................................................................................................126
9.3.4
Regulatory Reporting Requirements for SAE ...................................................127
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9.3.5
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs................................................................................127
9.3.6
Pregnancy and Exposure During Breastfeeding ................................................127
9.3.7
Events of Clinical Interest (ECIs)......................................................................127
9.4
Treatment of Overdose.........................................................................................128
9.5
Safety......................................................................................................................128
9.5.1
Physical Examinations.......................................................................................128
9.5.2
Vital Signs..........................................................................................................128
9.5.3
Electrocardiograms ............................................................................................129
9.5.4
Clinical Safety Laboratory Assessments............................................................129
9.5.4.1
Laboratory Safety Evaluations (Hematology, Chemistry, and 
Urinalysis)...................................................................................................129
9.5.4.2
Pregnancy Testing.......................................................................................129
9.6
130
9.7
Pharmacodynamics...............................................................................................130
9.8
130
9.9
131
9.10
Visit Requirements................................................................................................131
9.10.1 Screening Period ................................................................................................131
9.10.2 Treatment Period................................................................................................132
9.10.3 Discontinued Participants Continuing to be Monitored in the Study ................132
9.10.3.1 Safety Follow-Up Visit...............................................................................132
9.10.3.2 Imaging Follow-Up Visits ..........................................................................132
9.10.3.3 Survival Follow-Up Visits..........................................................................133
9.10.4 Survival Status ...................................................................................................133
10.
Statistical Analysis Plan ..........................................................................................133
10.1
Statistical Analysis Plan Summary......................................................................133
10.2
Responsibility for Analyses/In-House Blinding..................................................136
10.3
Hypotheses/Estimation .........................................................................................136
10.4
Analysis Endpoints................................................................................................136
10.4.1 Efficacy/Immunogenicity/Pharmacokinetics Endpoints....................................136
10.4.2 Safety Endpoints ................................................................................................137
10.5
Analysis Populations.............................................................................................137
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10.5.1 Safety Analysis Populations ..............................................................................137
10.5.2 Pharmacokinetic Analysis Populations..............................................................137
10.5.3 Efficacy Analysis Populations ...........................................................................138
10.6
Statistical Methods................................................................................................138
10.6.1 Statistical Methods for Efficacy Analysis..........................................................138
10.6.2 Statistical Methods for Safety Analysis.............................................................138
10.6.3 Summaries of Baseline Characteristics, Demographics, and Other 
Analyses.............................................................................................................139
10.6.3.1 Demographic and Baseline Characteristics ................................................139
10.6.3.2
139
10.7
Interim Analyses ...................................................................................................139
10.8
Multiplicity ............................................................................................................140
10.9
Sample Size and Power Calculations ..................................................................140
10.10 Subgroup Analyses................................................................................................141
10.11 Compliance (Medication Adherence)..................................................................141
10.12 Extent of Exposure................................................................................................141
11.
References.................................................................................................................142
12.
Appendices................................................................................................................147
12.1
Appendix 1: Study Governance Considerations ................................................147
Code of Conduct for Clinical Trials...............................................................................147
Financial Disclosure.......................................................................................................149
Data Protection...............................................................................................................150
Confidentiality of Data ..................................................................................................150
Confidentiality of Participant Records...........................................................................150
Confidentiality of IRB/IEC Information........................................................................150
Publication Policy..........................................................................................................151
Compliance with Study Registration and Results Posting Requirements .....................151
Compliance with Law, Audit and Debarment ...............................................................151
Data Quality Assurance .................................................................................................152
Source Documents .........................................................................................................153
Study and Site Closure...................................................................................................153
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12.2
Appendix 2: Collection and Management of Specimens for Future 
Biomedical Research.............................................................................................154
12.3
Appendix 3: Contraceptive Guidance and Pregnancy Testing.........................159
Definitions......................................................................................................................159
Contraception Requirements..........................................................................................159
Pregnancy Testing..........................................................................................................162
12.4
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting............................................163
Definition of AE ............................................................................................................163
Definition of SAE ..........................................................................................................164
Additional Events Reported in the Same Manner as SAE.............................................165
Recording AE and SAE .................................................................................................165
Reporting of AE, SAE, and Other Reportable Safety Events to the Sponsor................169
12.5
Appendix 5: Clinical Laboratory Tests...............................................................170
12.6
Appendix 6: Country-Specific Requirements.....................................................172
12.7
Appendix 7: Description of the iRECIST Process for Assessment of 
Disease Progression...............................................................................................173
12.8
Appendix 8: Abbreviations and Trademarks.....................................................177
12.9
MASCC 2016 Guidelines......................................................................................180
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LIST OF TABLES
Table 1
Pharmacokinetic Parameter Estimates Used in Prediction of Human 
Exposure (Cmax) to MK-5890 ...............................................................................74
Table 2
Whole Body Saturation Corresponding to Predicted Maximum 
Concentration Upon MK-5890 Dosing in Humans..............................................75
Table 3
Chemotherapy Dose Level Definitions ................................................................78
Table 4
Dose-Finding Rules per the Modified Toxicity Probability Interval 
Design...................................................................................................................80
Table 5
Adequate Organ Function Laboratory Values......................................................86
Table 6
Study Treatments..................................................................................................92
Table 7
MK-5890 Dose Modification and Treatment Discontinuation 
Guidelines for Drug-Related Adverse Events ......................................................99
Table 8
Dose Modification and Toxicity Management Guidelines for Immune-
related Adverse Events Associated With Pembrolizumab Monotherapy, 
Coformulations or IO Combinations ..................................................................101
Table 9
Infusion Reaction Treatment Guidelines............................................................105
Table 10
Recommended Dose Modifications for Chemotherapy-Related 
Hematological Toxicities....................................................................................107
Table 11
Recommended Dose Modifications for Chemotherapy-Related 
Non-Hematological Toxicities............................................................................107
Table 12
Imaging and Treatment After First Radiologic Evidence of Progressive 
Disease................................................................................................................123
Table 13
Reporting Time Periods and Timeframes for Adverse Events and Other 
Reportable Safety Events....................................................................................126
Table 14
Confidence Intervals of the True ORR Under Different Hypothetical 
Numbers of Observed Response Scenarios ........................................................141
Table 15
Highly Effective Contraception Methods...........................................................161
Table 16
Protocol-Required Safety Laboratory Assessments ...........................................171
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LIST OF FIGURES
Figure 1
Mechanism of Action of the CD27/CD70 Co-Stimulatory System in 
Regulation of the T Cell Response.......................................................................56
Figure 2
Study Design.........................................................................................................65
Figure 3
Imaging and Treatment for Clinically Stable Participants After First 
Radiologic Evidence of Progressive Disease .....................................................124
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1. SYNOPSIS
Protocol Title:  
A Phase 1 Study of MK-5890 as Monotherapy and in Combination with Pembrolizumab 
in Participants with Advanced Solid Tumors
Short Title: 
A Phase 1 Study of MK-5890 as Monotherapy and in Combination with Pembrolizumab
Objectives/Hypotheses and Endpoints:
In male and female participants with advanced solid tumors who are at least 18 years of age:
Objectives
Endpoints
Primary

Objective: To determine the safety and 
tolerability and to establish a
preliminary recommended Phase 2 dose
(RP2D) of MK-5890 when used as 
monotherapy and in combination with 
pembrolizumab in the dose escalation 
and confirmation phase and the dose 
expansion phase

Number of participants with a 
dose-limiting toxicity (DLT)

Number of participants with ≥1 adverse 
event (AE)

Number of participants who discontinue
study treatment due to an AE
Secondary

Objective: To evaluate the PK of 
MK-5890 when given by IV infusion as 
monotherapy, in combination with 
pembrolizumab, and in combination 
with pembrolizumab, pemetrexed and 
carboplatin and in combination with 
pembrolizumab and nab-paclitaxel, in 
the dose escalation and confirmation 
phase and/or the dose expansion phase

PK parameters including area under the 
curve (AUC), minimum concentration 
(Cmin), and maximum concentration 
(Cmax)

Objective: To evaluate the objective 
response rate (ORR) of MK-5890 when 
used as monotherapy, in combination 
with pembrolizumab, in combination 
with pembrolizumab and nab-paclitaxel
in the dose expansion phase

ORR as assessed by the investigator 
based on Response Evaluation Criteria in 
Solid Tumors, version 1.1 (RECIST 1.1)
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Objectives
Endpoints

Objective: To determine the safety and 
tolerability of MK-5890 in combination 
with pembrolizumab, pemetrexed, and 
carboplatin in participants with 
nonsquamous NSCLC and to establish 
maximum tolerated doses (MTDs) of 
carboplatin and pemetrexed when used 
in combination with MK-5890 and 
pembrolizumab

Number of participants with a DLT

Number of participants with ≥1 AE

Number of participants who discontinue
study treatment due to an AE

Objective: To determine the safety and 
tolerability of MK-5890 in combination 
with pembrolizumab and nab-paclitaxel
in participants with locally recurrent 
inoperable TNBC cancer not previously 
treated with chemotherapy and which 
cannot be treated with curative intent or 
with  previously not treated metastatic 
TNBC and to establish MTDs of nab-
paclitaxel when used in combination 
with MK-5890 and pembrolizumab

Number of participants with a DLT

Number of participants with ≥1 AE

Number of participants who discontinue 
study treatment due to an AE
Overall Design:
Study Phase
Phase 1
Clinical Indication
Dose escalation and confirmation phase: The treatment of 
participants with advanced solid tumors
Dose expansion phase: The treatment of participants with 
triple-negative breast cancer (TNBC), nonsquamous NSCLC or 
endometrial cancer
Population
Participants with a histologically or cytologically confirmed 
advanced/metastatic solid tumor by pathology report who have 
received or been intolerant to all treatment known to confer 
clinical benefit. Participants in the expansion phase (Arm 4) 
have locally recurrent inoperable TNBC not previously treated 
with chemotherapy and which cannot be treated with curative 
intent or with not previously treated metastatic TNBC
Study Type
Interventional
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Type of Design
Multi-site, multi-arm, dose escalation, dose confirmation, dose 
expansion study
Type of Control
No treatment control
Study Blinding
Unblinded open-label
Estimated Duration 
of Study
The Sponsor estimates that the study will require approximately 
6.0 years from the time the first participant (or their legally 
acceptable representative) provides documented informed 
consent until the last participant’s last study-related contact.  
Number of Participants:
Approximately 202 participants will be enrolled.
Treatment Groups and Duration:
Treatment Groups
Participants in the dose escalation/dose confirmation phase will 
be allocated to 1 of 2 treatment arms:
Arm 1: Escalating doses of MK-5890 given once every 
3 weeks (Q3W) as monotherapy; or
Arm 2: Escalating doses of MK-5890 in combination with 
200 mg pembrolizumab, both given Q3W.
Participants in the dose escalation/dose confirmation phase with 
nonsquamous non-small cell lung cancer (NSCLC) enrolled as 
part of Amendment 02 will be allocated to:
Arm 3: 30 mg MK-5890 in combination with 200 mg 
pembrolizumab, 500 mg/m2 pemetrexed, and 
AUC 5 mg/mL/min carboplatin, all given Q3W.
Participants in the dose expansion phase with TNBC will be 
allocated to:
Arm 2a: 30 mg MK-5890 in combination with 200 mg 
pembrolizumab, both given Q3W.
Arm 4: 30 mg MK-5890 in combination with 400 mg 
pembrolizumab, 100 mg/m2 nab-paclitaxel.  MK-5890 and 
pembrolizumab given Q6W for 18 cycles.  Nab-paclitaxel 
administered on a 3-week on (Days 1, 8 and 15)/ 1-week off 
schedule every 28 days.  
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Participants in the dose expansion phase with endometrial cancer 
will be allocated to:
Arm 1a: 30 mg MK-5890 given Q3W as monotherapy;
Arm 2b: 30 mg MK-5890 in combination with 200 mg 
pembrolizumab, both given Q3W; or
Arm 2c: 30 mg MK-5890 in combination with 400 mg 
pembrolizumab, both given once every 6 weeks (Q6W).
Duration of 
Participation
Each participant will participate in the study from the time the 
participant provides documented informed consent form (ICF) 
through the final protocol-specified contact.
After a screening period of up to 28 days, each participant will 
be assigned to receive study treatment until disease progression, 
unacceptable AEs, intercurrent illness that prevents further 
administration of treatment, investigator’s decision to withdraw
treatment, participant withdrawal of consent, pregnancy, 
noncompliance with study treatment or procedure requirements,
the participant completes study treatment, administrative reasons 
requiring cessation of treatment, or death.
After the end of treatment, each participant will be followed for 
the occurrence of AEs and spontaneously reported pregnancy as 
described in Section 9.3.
Participants who discontinue study treatment for reasons other 
than confirmed disease progression will have post-treatment 
follow-up imaging every 9 weeks for disease status until disease 
progression, initiating a new anticancer therapy, participant 
withdrawal of consent, pregnancy, becoming lost to follow-up, 
or death.
After confirmed disease progression, each participant will be 
contacted by telephone approximately every 12 weeks for 
survival until participant withdrawal of consent, becoming lost 
to follow-up, death, or the end of the study.
Study governance considerations are outlined in Appendix 1. A list of abbreviations used in 
this document can be found in Appendix 8.
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2. SCHEDULE OF ACTIVITIES (SOA)
2.1
Schedule of Activities for the Screening & Treatment Periods - Dose Escalation and Confirmation Phase (Arms 1 and 2)
Note: Participants in Arms 1 and 2 of the dose escalation and confirmation phase will follow the SoA in Section 2.7 for the End of 
Treatment and Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2 3 5 8 15 1
2 3 5 8 15
Every 
9 weeks
1
Administrative Procedures
Informed Consent
X
Documented informed consent must be obtained prior to performing any 
protocol-specific procedures. Tests performed prior to consent as part of 
routine clinical management are acceptable if performed within the specified 
timeframe.
Informed Consent for 
Future Biomedical Research (FBR)
X
Inclusion/Exclusion Criteria
X
Participant Identification Card
X
Demographics and Medical History
X
Oncology Disease Status and Prior 
Oncology Treatment History
X
Concomitant Medication
X
X X
X X X X
X X
X
Clinical Procedures/Assessments
Physical Examination
X
X2
X2
X2
A full physical examination should be done at screening. Directed physical 
examinations may be done at the other time points unless a full examination 
is deemed necessary. 
Height
X
Weight
X
X
X
X
Vital Signs
X
X X X
X X X X X
X X
X
To be measured at screening and prior to dosing, and 2 hours, 4 hours, and 
6 hours after the start of the MK-5890 infusion on Day 1 and once daily on 
Day 2, Day 3, Day 8, and Day 15 of Cycles 1-4. In Cycles ≥5, measured 
prior to dosing on Day 1 only. Measurements include temperature, pulse, 
respiratory rate, blood pressure.
ECOG Performance Status
X
X2
X2
X2
Should be performed at screening and prior to dosing on Day 1 of each 
cycle.
12-Lead Electrocardiogram
X
X2
X2
Performed at screening and prior to dosing and within 30 minutes after the 
end of the MK-5890 infusion on Day 1 of Cycles 1-4.
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2 3 5 8 15 1
2 3 5 8 15
Every 
9 weeks
1
 
 
 
 
 
 
Adverse Event Monitoring
X
X X X
X X X X X
X X
X
All adverse events that occur after the consent form is signed but before 
treatment allocation must be reported by the investigator if the event causes 
the participant to be excluded from the study or is the result of a 
protocol-specified intervention. Continuous AE reporting from the time of 
treatment allocation.
Tumor Imaging and
Response Assessment
X
X
X
At screening and every 9 weeks from the first dose of study treatment.
Survival Status
Upon Sponsor request, participants may be contacted for survival status at 
any time during the course of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2 X
X X X2
X X
X2
To be collected at screening and prior to dosing and 4 hours after the start of 
the MK-5890 infusion on Day 1 of Cycles 1-4. In Cycle 1, should also be 
collected once daily on Day 2, Day 8, and Day 15. In Cycles 2-4, should 
also be collected once daily on Day 8 and Day 15. In Cycles ≥5, to be 
collected prior to dosing on Day 1 only.
Chemistry Panel
X1
X2 X
X X X2
X X
X2
Prothrombin Time (PT)/International 
Normalized Ratio (INR) and 
Activated Partial Thromboplastin 
Time (aPTT)
X1
Participants on anticoagulant therapy should be monitored throughout the
study.
Lactate Dehydrogenase (LDH) and 
Gamma Glutamyl Transferase (GGT)
X1
X2
X2
X2
Thyroid Function Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are collected every other cycle.
Pregnancy Test (urine or serum β-
human chorionic gonadotropin [β-
hCG]) - Women of childbearing 
potential only
X
X2
Urine pregnancy test to be performed as indicated; if test is positive or 
cannot be confirmed as negative, a serum pregnancy test is required. 
Monthly testing should be conducted per local regulations.
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2 3 5 8 15 1
2 3 5 8 15
Every 
9 weeks
1
HIV/Hepatitis Screen
(at the discretion of the investigator)
X
Per local regulations.
Urinalysis
X1
Blood for RNA Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-5.
Serum for Biomarker Analyses3
X
X X
X
X X
X
X
To be collected at screening and prior to dosing and 2 hours after the start of 
the MK-5890 infusion on Day 1 and once daily on Day 2 and Day 8 of 
Cycles 1-4. In Cycles ≥5, to be collected prior to dosing and 2 hours after 
the start of the MK-5890 infusion on Day 1 only.
Peripheral Blood Mononuclear Cell 
(PBMC) Collection for Biomarker 
Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-4 and every 4 cycles 
thereafter. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
Blood for Immunophenotyping3
X
X
X X X
X X
X
To be collected at screening and prior to dosing on Day 1 and once daily on 
Day 8 and Day 15 of Cycles 1-4. In Cycles ≥5, to be collected prior to 
dosing on Day 1 only. An additional sample will be collected to coincide 
with the optional post-treatment tumor biopsy.
Blood for Genetic Analyses
X
If there is either a documented law or regulation prohibiting collection of 
blood for genetic analyses, or if the IRB/IEC does not approve the 
collection, sampling will not be done at the site. If the planned genetic 
analysis is not approved, but FBR is approved and consent is given, this 
sample will be collected for the purpose of FBR only.
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2 3 5 8 15 1
2 3 5 8 15
Every 
9 weeks
1
Tumor Tissue Collection
X
Required at screening for all participants. Newly obtained tumor tissue is 
defined as tissue collected within 90 days before the first dose of study 
treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is 
not required to be at the study site within the 28-day screening period.
Post-Treatment Tumor Biopsy
X
Requested between Day 8 and Day 15 of Cycle 2.
Blood for Receptor Availability 
Analysis3
X
X X X X X X X X X X X X
X
To be collected at screening and prior to dosing at the end of the MK-5890 
infusion (+10 minutes) and 2 hours after the start of the MK-5890 infusion 
(+/-10 minutes) on Day 1, and once daily on Day 2, Day 3, Day 5, Day 8, 
and Day 15 of Cycles 1-4. In addition, samples should be collected prior to 
dosing on Day 1 of Cycles 5 and 6.
Serum for Soluble Receptor Analysis3
X
X X X X X X X X X X X X
X
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
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2.2
Schedule of Activities for the Screening & Treatment Periods – Dose Escalation and Confirmation Phase (Arm 3: 
30 mg MK-5890 + 200 mg Pembrolizumab + 500 mg/m2 Pemetrexed + AUC 5 mg/mL/min Carboplatin, all Q3W in 
Participants With Nonsquamous NSCLC)
Note: Participants in Arm 3 of the dose escalation and confirmation phase will follow the SoA in Section 2.7 for the End of Treatment 
and Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles 
≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
2
3
8
15
Every 
9 weeks
1
Administrative Procedures
Informed Consent
X
Documented informed consent must be obtained prior to performing any 
protocol-specific procedures. Tests performed prior to consent as part of routine 
clinical management are acceptable if performed within the specified timeframe.
Informed Consent for 
Future Biomedical Research (FBR)
X
Inclusion/Exclusion Criteria
X
Participant Identification Card
X
Demographics and Medical History
X
Oncology Disease Status and Prior 
Oncology Treatment History
X
Concomitant Medication
X
X X
X
X
X X
X X
X
Clinical Procedures/Assessments
Physical Examination
X
X2
X2
X2
A full physical examination should be done at screening. Directed physical 
examinations may be done at the other time points unless a full examination is 
deemed necessary. 
Height
X
Weight
X
X
X
X
Vital Signs
X
X X X X
X
X X X X X
X
To be measured at screening and prior to dosing and 2 hours, 4 hours, and 
6 hours after the start of the MK-5890 infusion on Day 1, and once daily on 
Day 2, Day 3, Day 8, and Day 15 of Cycles 1-4. In Cycles ≥5, measured prior to 
dosing on Day 1 only. Measurements include temperature, pulse, respiratory 
rate, blood pressure.
ECOG Performance Status
X
X2
X2
X2
Should be performed at screening and prior to dosing on Day 1 of each cycle.
12-Lead Electrocardiogram
X
X2
X2
Performed at screening and prior to dosing and within 30 minutes after the end 
of the MK-5890 infusion on Day 1 of Cycles 1-4.
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles 
≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
2
3
8
15
Every 
9 weeks
1
 
 
 
 
 
 
 
 
 
 
Pemetrexed Drug Administration
X
X
X
Carboplatin Drug Administration
X
X
Adverse Event Monitoring
X
X X X X
X
X X X X X
X
All adverse events that occur after the consent form is signed but before 
treatment allocation must be reported by the investigator if the event causes the 
participant to be excluded from the study or is the result of a protocol-specified 
intervention. Continuous AE reporting from the time of treatment allocation.
Tumor Imaging and
Response Assessment
X
X
X
At screening and every 9 weeks from the first dose of study treatment.
Survival Status
Upon Sponsor request, participants may be contacted for survival status at any 
time during the course of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2 X
X
X X2
X X
X2
To be collected at screening and prior to dosing and 4 hours after the start of the 
MK-5890 infusion on Day 1 of Cycles 1-4. In Cycle 1, should also be collected 
once daily on Day 2, Day 8, and Day 15. In Cycles 2-4, should also be collected 
once daily on Day 8 and Day 15. In Cycles ≥5, to be collected prior to dosing on 
Day 1 only.
Chemistry Panel
X1
X2 X
X
X X2
X X
X2
Prothrombin Time (PT)/International 
Normalized Ratio (INR) and Activated 
Partial Thromboplastin Time (aPTT)
X1
Participants on anticoagulant therapy should be monitored throughout the study.
Lactate Dehydrogenase (LDH) and 
Gamma Glutamyl Transferase (GGT)
X1
X2
X2
X2
Creatinine Clearance (CrCl) 
Calculation
X1
X2
X2
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles 
≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
2
3
8
15
Every 
9 weeks
1
Thyroid Function Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are collected every other cycle.
Pregnancy Test (urine or serum β-
human chorionic gonadotropin [β-
hCG]) - Women of childbearing 
potential only
X
X2
Urine pregnancy test to be performed as indicated; if test is positive or cannot be 
confirmed as negative, a serum pregnancy test is required. Monthly testing 
should be conducted per local regulations.
HIV/Hepatitis Screen
(at the discretion of the investigator)
X
Per local regulations.
Urinalysis
X1
Laboratory Procedures/Assessments – CENTRAL
Pharmacokinetic Sampling for 
Pemetrexed3
X X
X X
X
Samples for pemetrexed PK testing should be collected prior to dosing and at 
the end of the pemetrexed infusion (+10 minutes) on Day 1 and once on Day 2 
of Cycles 1 and 2 and prior to dosing and at the end of the pemetrexed infusion 
(+10 minutes) on Day 1 of Cycle 8.
Pharmacokinetic Sampling for 
Carboplatin3
X X
X X
Samples for carboplatin PK testing should be collected prior to dosing and at the 
end of the carboplatin infusion (+10 minutes) on Day 1 and once on Day 2 of 
Cycles 1 and 2.
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles 
≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
2
3
8
15
Every 
9 weeks
1
Blood for circulating tumor DNA 
(ctDNA) Analysis
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-5.
Blood for RNA Analyses
X
X
X
Serum for Biomarker Analyses3
X
X X
X
X
X
To be collected at screening and prior to dosing and 2 hours after the start of the 
MK-5890 infusion on Day 1 and once daily on Day 2 and Day 8 of Cycle 1. In 
Cycles 2-8, to be collected prior to dosing and 2 hours after the start of the 
MK-5890 infusion on Day 1 only.
Peripheral Blood Mononuclear Cell 
(PBMC) Collection for Biomarker 
Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-4 and every 4 cycles 
thereafter. An additional sample will be collected to coincide with the optional 
post-treatment tumor biopsy.
Blood for Immunophenotyping3
X
X
X
X
X
X
To be collected at screening and prior to dosing on Day 1, and once daily on 
Day 8 and Day 15 of Cycle 1. In Cycles 2-8, to be collected prior to dosing on 
Day 1 only. An additional sample will be collected to coincide with the optional 
post-treatment tumor biopsy.
Blood for Genetic Analyses
X
If there is either a documented law or regulation prohibiting collection of blood 
for genetic analyses, or if the IRB/IEC does not approve the collection, sampling 
will not be done at the site. If the planned genetic analysis is not approved, but 
FBR is approved and consent is given, this sample will be collected for the 
purpose of FBR only.
Tumor Tissue Collection
X
Required at screening for all participants. Newly obtained tumor tissue is 
defined as tissue collected within 90 days before the first dose of study 
treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is not 
Serum for Soluble Receptor Analysis3
X
X X X X
X
X
X
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
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2.3
Schedule of Activities for the Screening & Treatment Periods - Dose Expansion Phase (Arm 1a: 30 mg MK-5890 Q3W 
as Monotherapy in Participants With Endometrial Cancer)
Note: Participants in Arm 1a of the dose expansion phase will follow the SoA in Section 2.7 for the End of Treatment and 
Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Administrative Procedures
Informed Consent
X
Documented informed consent must be obtained prior to performing any 
protocol-specific procedures. Tests performed prior to consent as part of 
routine clinical management are acceptable if performed within the 
specified timeframe.
Informed Consent for
Future Biomedical Research (FBR)
X
Inclusion/Exclusion Criteria
X
Participant Identification Card
X
Demographics and Medical History
X
Oncology Disease Status and Prior Oncology 
Treatment History
X
Concomitant Medication
X
X X
X X
X X X
X
Clinical Procedures/Assessments
Physical Examination
X
X2
X2
X2
A full physical examination should be done at screening. Directed physical 
examinations may be done at the other time points unless a full 
examination is deemed necessary. 
Height
X
Weight
X
X
X
X
Vital Signs
X
X X X X X
X X X
X
To be measured at screening and prior to dosing and 2 hours, 4 hours, and 
6 hours after the start of the MK-5890 infusion on Day 1, and once daily on 
Day 2, Day 3, Day 8, and Day 15 of Cycle 1. In Cycles 2-4, measured prior 
to dosing and 2 hours, 4 hours, and 6 hours after the start of the MK-5890 
infusion on Day 1 and once daily on Day 8 and Day 15. In Cycles ≥5, 
measured prior to dosing on Day 1 only. Measurements include 
temperature, pulse, respiratory rate, blood pressure.
ECOG Performance Status
X
X2
X2
X2
Should be performed at screening and prior to dosing on Day 1 of each 
cycle.
12-Lead Electrocardiogram
X
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Adverse Event Monitoring
X
X X X X X
X X X
X
All adverse events that occur after the consent form is signed but before 
treatment allocation must be reported by the investigator if the event causes 
the participant to be excluded from the study or is the result of a 
protocol-specified intervention. Continuous AE reporting from the time of 
treatment allocation.
Tumor Imaging and
Response Assessment
X
X
X
At screening and every 9 weeks from the first dose of study treatment.
Survival Status
Upon Sponsor request, participants may be contacted for survival status at 
any time during the course of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2 X
X X X2 X X
X2
To be collected at screening and prior to dosing and 4 hours after the start 
of the MK-5890 infusion on Day 1 of Cycles 1-4. In Cycle 1, should also 
be collected once daily on Day 2, Day 8, and Day 15. In Cycles 2-4, should 
also be collected once daily on Day 8 and Day 15. In Cycles ≥5, to be 
collected prior to dosing on Day 1 only.
Chemistry Panel
X1
X2 X
X X X2 X X
X2
Prothrombin Time (PT)/International 
Normalized Ratio (INR) and Activated Partial 
Thromboplastin Time (aPTT)
X1
Participants on anticoagulant therapy should be monitored throughout the
study.
Lactate Dehydrogenase (LDH) and Gamma 
Glutamyl Transferase (GGT)
X1
X2
X2
X2
Thyroid Function Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are collected every other cycle.
Pregnancy Test (urine or serum β-human 
chorionic gonadotropin [β-hCG]) - Women of 
childbearing potential only
X
X2
Urine pregnancy test to be performed as indicated; if test is positive or 
cannot be confirmed as negative, a serum pregnancy test is required. 
Monthly testing should be conducted per local regulations.
HIV/Hepatitis Screen
(at the discretion of the investigator)
X
Per local regulations.
Urinalysis
X1
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Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Laboratory Procedures/Assessments – CENTRAL
Blood for circulating tumor DNA (ctDNA) 
Analysis
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-5.
Blood for RNA Analyses
X
X
X
Serum for Biomarker Analyses3
X
X X
X
X
X
To be collected at screening and prior to dosing and 2 hours after the start 
of the MK-5890 infusion on Day 1 and once daily on Day 2 and Day 8 of 
Cycle 1. In Cycles ≥2, to be collected prior to dosing and 2 hours after the 
start of the MK-5890 infusion on Day 1 only.
Peripheral Blood Mononuclear Cell (PBMC) 
Collection for Biomarker Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-4 and every 4 cycles 
thereafter. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
Blood for Immunophenotyping3
X
X
X X
X
X
To be collected at screening and prior to dosing on Day 1 and once daily on 
Day 8 and Day 15 of Cycle 1. In Cycles ≥2, to be collected prior to dosing 
on Day 1 only. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
Blood for Genetic Analyses
X
If there is either a documented law or regulation prohibiting collection of 
blood for genetic analyses, or if the IRB/IEC does not approve the 
collection, sampling will not be done at the site. If the planned genetic 
analysis is not approved, but FBR is approved and consent is given, this 
sample will be collected for the purpose of FBR only.
Tumor Tissue Collection
X
Required at screening for all participants. Newly obtained tumor tissue is 
defined as tissue collected within 90 days before the first dose of study 
treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is 
not required to be at the study site within the 28-day screening period.
Post-Treatment Tumor Biopsy
X
Requested between Day 8 and Day 15 of Cycle 2.
CCI
08XZ0Q

Product:  MK-5890 
30
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Serum for Soluble Receptor Analysis3
X
X X X X X
X
X
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
CCI
CCI
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Product:  MK-5890 
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Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
2.4
Schedule of Activities for the Screening & Treatment Periods - Dose Expansion Phase (Arm 2a: 30 mg MK-5890 +
200 mg Pembrolizumab, Both Q3W in Participants With TNBC AND Arm 2b: 30 mg MK-5890 + 200 mg 
Pembrolizumab, Both Q3W in Participants With Endometrial Cancer)
Note: Participants in Arms 2a and 2b of the dose expansion phase will follow the SoA in Section 2.7 for the End of Treatment and 
Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Administrative Procedures
Informed Consent
X
Documented informed consent must be obtained prior to performing any 
protocol-specific procedures. Tests performed prior to consent as part of 
routine clinical management are acceptable if performed within the 
specified timeframe.
Informed Consent for
Future Biomedical Research (FBR)
X
Inclusion/Exclusion Criteria
X
Participant Identification Card
X
Demographics and Medical History
X
Oncology Disease Status and Prior Oncology 
Treatment History
X
Concomitant Medication
X
X X
X X
X X X
X
Clinical Procedures/Assessments
Physical Examination
X
X2
X2
X2
A full physical examination should be done at screening. Directed physical 
examinations may be done at the other time points unless a full 
examination is deemed necessary. 
Height
X
Weight
X
X
X
X
Vital Signs
X
X X X X X
X X X
X
To be measured at screening and prior to dosing and 2 hours, 4 hours, and 
6 hours after the start of the MK-5890 infusion on Day 1, and once daily on 
Day 2, Day 3, Day 8, and Day 15 of Cycle 1. In Cycles 2-4, measured prior 
to dosing and 2 hours, 4 hours, and 6 hours after the start of the MK-5890 
infusion on Day 1, and once daily on Day 8 and Day 15. In Cycles ≥5, 
measured prior to dosing on Day 1 only. Measurements include 
temperature, pulse, respiratory rate, blood pressure.
ECOG Performance Status
X
X2
X2
X2
Should be performed at screening and prior to dosing on Day 1 of each 
cycle.
12-Lead Electrocardiogram
X
08XZ0Q

Product:  MK-5890 
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Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Adverse Event Monitoring
X
X X X X X
X X X
X
All adverse events that occur after the consent form is signed but before 
treatment allocation must be reported by the investigator if the event causes 
the participant to be excluded from the study or is the result of a 
protocol-specified intervention. Continuous AE reporting from the time of 
treatment allocation.
Tumor Imaging and
Response Assessment
X
X
X
At screening and every 9 weeks from the first dose of study treatment.
Survival Status
Upon Sponsor request, participants may be contacted for survival status at 
any time during the course of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2 X
X X X2 X X
X2
To be collected at screening and prior to dosing and 4 hours after the start 
of the MK-5890 infusion on Day 1 of Cycles 1-4. In Cycle 1, should also 
be collected once daily on Day 2, Day 8, and Day 15. In Cycles 2-4, should 
also be collected once daily on Day 8 and Day 15. In Cycles ≥5, to be 
collected prior to dosing on Day 1 only.
Chemistry Panel
X1
X2 X
X X X2 X X
X2
Prothrombin Time (PT)/International 
Normalized Ratio (INR) and Activated Partial 
Thromboplastin Time (aPTT)
X1
Participants on anticoagulant therapy should be monitored throughout the
study.
Lactate Dehydrogenase (LDH) and Gamma 
Glutamyl Transferase (GGT)
X1
X2
X2
X2
Thyroid Function Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are collected every other cycle.
Pregnancy Test (urine or serum β-human 
chorionic gonadotropin [β-hCG]) - Women of 
childbearing potential only
X
X2
Urine pregnancy test to be performed as indicated; if test is positive or 
cannot be confirmed as negative, a serum pregnancy test is required. 
Monthly testing should be conducted per local regulations.
HIV/Hepatitis Screen
(at the discretion of the investigator)
X
Per local regulations.
Urinalysis
X1
CCI
08XZ0Q

Product:  MK-5890 
33
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Laboratory Procedures/Assessments – CENTRAL
Blood for circulating tumor DNA (ctDNA) 
Analysis
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-5.
Blood for RNA Analyses
X
X
X
Serum for Biomarker Analyses3
X
X X
X
X
X
To be collected at screening and prior to dosing and 2 hours after the start 
of the MK-5890 infusion on Day 1 and once daily on Day 2 and Day 8 of 
Cycle 1. In Cycles 2-8, to be collected prior to dosing and 2 hours after the 
start of the MK-5890 infusion on Day 1 only.
Peripheral Blood Mononuclear Cell (PBMC) 
Collection for Biomarker Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-4 and every 4 cycles 
thereafter. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
Blood for Immunophenotyping3
X
X
X X
X
X
To be collected at screening and prior to dosing on Day 1 and once daily on 
Day 8 and Day 15 of Cycle 1. In Cycles 2-8, to be collected prior to dosing 
on Day 1 only. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
CCI
08XZ0Q

Product:  MK-5890 
34
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 21 days
Notes
Visit Timing
Up to 28 days 
prior to 1st dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15
1
8
15
Every 
9 weeks
1
Blood for Genetic Analyses
X
If there is either a documented law or regulation prohibiting collection of 
blood for genetic analyses, or if the IRB/IEC does not approve the 
collection, sampling will not be done at the site. If the planned genetic 
analysis is not approved, but FBR is approved and consent is given, this 
sample will be collected for the purpose of FBR only.
Tumor Tissue Collection
X
Required at screening for all participants. Newly obtained tumor tissue is 
defined as tissue collected within 90 days before the first dose of study 
treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is 
not required to be at the study site within the 28-day screening period.
Post-Treatment Tumor Biopsy
X
Requested between Day 8 and Day 15 of Cycle 2.
Serum for Soluble Receptor Analysis3
X
X X X X X
X
X
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
CCI
CCI
08XZ0Q

Product:  MK-5890 
35
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
2.5
Schedule of Activities for the Screening & Treatment Periods - Dose Expansion Phase (Arm 2c: 30 mg MK-5890 +
400 mg Pembrolizumab, Both Q6W in Participants With Endometrial Cancer)
Note: Participants in Arm 2c of the dose expansion phase will follow the SoA in Section 2.7 for the End of Treatment and 
Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15 22 29 36
1
2
8
15
22
Every 
9 weeks
1
Administrative Procedures
Informed Consent
X
Documented informed consent must be obtained prior to performing any 
protocol-specific procedures. Tests performed prior to consent as part of 
routine clinical management are acceptable if performed within the specified 
timeframe.
Informed Consent for
Future Biomedical 
Research (FBR)
X
Inclusion/Exclusion 
Criteria
X
Participant Identification 
Card
X
Demographics and Medical 
History
X
Oncology Disease Status 
and Prior Oncology 
Treatment History
X
Concomitant Medication
X
X X
X X X X
X
X
X
X
X
X
X
Clinical Procedures/Assessments
Physical Examination
X
X2
X X
X
X2
X
X2
A full physical examination should be done at screening. Directed physical 
examinations may be done at the other time points unless a full examination 
is deemed necessary. 
Height
X
Weight
X
X
X X
X
X
X
X
08XZ0Q

Product:  MK-5890 
36
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15 22 29 36
1
2
8
15
22
Every 
9 weeks
1
Vital Signs
X
X X X X X X X
X
X
X
X
X
X
X
To be measured at screening and prior to dosing and 2 hours, 4 hours, and 
6 hours after the start of the MK-5890 infusion on Day 1, and once daily on 
Day 2, Day 3, Day 8, Day 15, Day 22, Day 29, and Day 36 of Cycle 1. In 
Cycles 2-4, measured prior to dosing, and 2 hours, 4 hours, and 6 hours after 
the start of the MK-5890 infusion on Day 1, and once daily on Day 2, Day 8, 
Day 15, and Day 22. In Cycles ≥5, measured prior to dosing on Day 1 only. 
Measurements include temperature, pulse, respiratory rate, blood pressure.
ECOG Performance Status
X
X2
X
X2
X
X2
Should be performed at screening and prior to dosing on Day 1 and once on 
Day 22 of Cycles 1-4. In Cycles ≥5, performed prior to dosing on Day 1 
only.
12-Lead Electrocardiogram
X
Adverse Event Monitoring
X
X X X X X X X
X
X
X
X
X
X
X
All adverse events that occur after the consent form is signed but before 
treatment allocation must be reported by the investigator if the event causes 
the participant to be excluded from the study or is the result of a 
protocol-specified intervention. Continuous AE reporting from the time of 
treatment allocation.
Tumor Imaging and
Response Assessment
X
X
X
At screening and every 9 weeks from the first dose of study treatment.
Survival Status
Upon Sponsor request, participants may be contacted for survival status at 
any time during the course of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2 X
X X X
X2
X
X
X
X2
To be collected at screening and prior to dosing and 4 hours after the start of 
the MK-5890 infusion on Day 1 of Cycles 1-4. In Cycle 1, should also be 
collected once daily on Day 2, Day 8, Day 15, and Day 22. In Cycles 2-4, 
should also be collected once daily on Day 8, Day 15, and Day 22. In 
Cycles ≥5, to be collected prior to dosing on Day 1 only. Additional 
sampling should be performed as clinically indicated.
Chemistry Panel
X1
X2 X
X X X
X2
X
X
X
X2
CCI
08XZ0Q

Product:  MK-5890 
37
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15 22 29 36
1
2
8
15
22
Every 
9 weeks
1
Prothrombin Time 
(PT)/International 
Normalized Ratio (INR) 
and Activated Partial 
Thromboplastin Time 
(aPTT)
X1
Participants on anticoagulant therapy should be monitored throughout the
study.
Lactate Dehydrogenase 
(LDH) and Gamma 
Glutamyl Transferase 
(GGT)
X1
X2
X2
X2
Thyroid Function Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are collected every other cycle.
Pregnancy Test (urine or 
serum β-human chorionic 
gonadotropin [β-hCG]) -
Women of childbearing 
potential only
X
X2
Urine pregnancy test to be performed as indicated; if test is positive or 
cannot be confirmed as negative, a serum pregnancy test is required. 
Monthly testing should be conducted per local regulations.
HIV/Hepatitis Screen (at 
the discretion of the 
investigator)
X
Per local regulations.
Urinalysis
X1
Laboratory Procedures/Assessments – CENTRAL
CCI
08XZ0Q

Product:  MK-5890 
38
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15 22 29 36
1
2
8
15
22
Every 
9 weeks
1
Blood for circulating tumor 
DNA (ctDNA) Analysis
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-5.
Blood for RNA Analyses
X
X
X
Serum for Biomarker 
Analyses3
X
X X
X
X
To be collected at screening and prior to dosing and 2 hours after the start of 
the MK-5890 infusion on Day 1 and once daily on Day 2 and Day 8 of 
Cycle 1. In Cycles 2-4, to be collected prior to dosing and 2 hours after the 
start of the MK-5890 infusion on Day 1 only.
Peripheral Blood 
Mononuclear Cell (PBMC) 
Collection for Biomarker 
Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycles 1-4 and every 2 cycles 
thereafter. An additional sample will be collected to coincide with the 
optional post-treatment tumor biopsy.
Blood for 
Immunophenotyping3
X
X
X X X
X
To be collected at screening and prior to dosing on Day 1 and once daily on 
Day 8, Day 15, and Day 22 of Cycle 1. In Cycles 2-4, to be collected prior to 
dosing on Day 1 only. An additional sample will be collected to coincide 
with the optional post-treatment tumor biopsy.
Blood for Genetic Analyses
X
If there is either a documented law or regulation prohibiting collection of 
blood for genetic analyses, or if the IRB/IEC does not approve the 
collection, sampling will not be done at the site. If the planned genetic 
analysis is not approved, but FBR is approved and consent is given, this 
sample will be collected for the purpose of FBR only.
Tumor Tissue Collection
X
Required at screening for all participants. Newly obtained tumor tissue is 
defined as tissue collected within 90 days before the first dose of study 
treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is 
not required to be at the study site within the 28-day screening period.
Post-Treatment Tumor 
Biopsy
X
Requested between Day 8 and Day 15 of Cycle 2.
CCI
08XZ0Q

Product:  MK-5890 
39
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 1st
dose
Cycle 1
Cycles 2-4
Cycles ≥5
Visit Window (Days)
-28 to -1
1
2
3
8
15 22 29 36
1
2
8
15
22
Every 
9 weeks
1
Serum for Soluble Receptor 
Analysis3
X
X X X X X X
X
X
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
CCI
CCI
08XZ0Q

Product:  MK-5890 
40
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
2.6
Schedule of Activities for the Screening & Treatment Periods - Cohort Expansion Phase (Arm 4: MK-5890 + 
Pembrolizumab, Both Q6W, Plus nab-Paclitaxel in Participants With Locally Recurrent Inoperable TNBC not 
Previously Treated With Chemotherapy and Which Cannot be Treated With Curative Intent or With not Previously 
Treated Metastatic TNBC Whose Tumor PD-L1 CPS is Less Than 10)
Note: Participants in Arm 4 of the dose expansion phase will follow the SoA in Section 2.7 for the End of Treatment and
Post-Treatment Follow-Up Periods.
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Administrative Procedures
Informed Consent
X
Documented informed consent 
must be obtained prior to 
performing any protocol-specific 
procedures. Tests performed prior 
to consent as part of routine 
clinical management are 
acceptable if performed within the 
specified timeframe.
Informed Consent 
for Future 
Biomedical 
Research (FBR)
X
Inclusion/Exclusion 
Criteria
X
Participant 
Identification Card
X
Demographics and 
Medical History
X
Oncology Disease 
Status and Prior 
Oncology 
Treatment History
X
08XZ0Q

Product:  MK-5890 
41
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Concomitant 
Medication
X
X
X
X X X
X X X X X X X X X X X X X X X X X X X X X X
X
X
X
Clinical Procedures/Assessments
Physical 
Examination
X
X2
X X X X X X
X X X X X X
X X X X X X
X X X
X
X
X
A full physical examination 
should be done at screening. 
Directed physical examinations
should be done weekly thereafter as
of Cycle 1, Day 1 unless a full
examination is deemed necessary.
Height
X
Weight
X
X
X
X
X
X
Measured at screening and prior to 
dosing on Day 1 of each cycle.
Vital Signsa
X
X
X
X X X X X X X X X X X X X X X X X X X X X X X X X
X
X
X
Measured at screening and prior to 
dosing and 2 hours, 4 hours, and 6 
hours after the start of MK-5890 
infusion on Day 1, and once daily 
on Day 2, Day 3, Day 8, Day 15, 
Day 22, Day 29, and Day 36 of 
Cycle 1. 
In Cycles 2-4, measured prior to 
dosing, and 2 hours, 4 hours, and 6 
hours after the start of MK-5890 
infusion on Day 1, and once daily 
on Day 2, Day 8, Day 15, Day 22, 
Day 29, and Day 36.
In Cycles ≥5, measured prior to 
dosing on Day 1 only.
a Includes temperature, pulse, 
respiratory rate, blood pressure.
ECOG 
Performance Status
X
X2
X
X
X
X
X
X
X
X
To be performed at screening and 
prior to dosing on Day 1 and once 
on Day 22 of Cycles 1-4.
In Cycles ≥5, performed prior to 
dosing on Day 1 only.
12-Lead 
Electrocardiogram
X
08XZ0Q

Product:  MK-5890 
42
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Every 
9 
1/8/15/
Nab-paclitaxel 
Drug 
Administration
X
X X
X X X
X X X
X
X X
X X X
X X
X
Xb
Nab-paclitaxel will be given on a 
3-week on/1-week off schedule 
every 28 days. Participants should 
receive premedication for nab-
paclitaxel per approved product 
labels.
b In odd-numbered cycles ≥5 (i.e., 
5, 7, 9, etc.), Nab-paclitaxel will 
be administered on Days 1, 8, 15, 
29, and 36. In even-numbered 
cycles ≥5 (i.e., 6, 8, 10, etc.), 
Nab-paclitaxel will be 
administered on Days 1, 15, 22, 
and 29.
CCI
08XZ0Q

Product:  MK-5890 
43
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Adverse Event 
Monitoring
X
X
X
X X X X X X X X X X X X X X X X X X X X X X X X X
X
X
X
All adverse events occurring after 
the consent form is signed but 
before treatment allocation must 
be reported by the investigator if 
the event causes the participant to 
be excluded from the study or is 
the result of a protocol-specified 
intervention. Continuous AE 
reporting from the time of 
treatment allocation.
Tumor Imaging and
Response 
Assessment
X
X
X
At screening and every 9 weeks 
from the first dose of study 
treatment.
Survival Status
Upon Sponsor request, 
participants may be contacted for 
survival status at any time during 
course of study.
08XZ0Q

Product:  MK-5890 
44
Protocol/Amendment No.: 001-06
MK-5890-001-06 Final Protocol
04-Aug-2022
Confidential
Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Laboratory Procedures/Assessments – LOCAL
Hematology
X1
X2
X
X X X X X X
X X X X X X
X X X X X X
X X X
X
X
X
Collected at screening and prior 
to dosing and 4 hours after the 
start of the MK-5890 infusion on 
Day 1 and once daily on Day 2 
(Cycle 1 only), Day 8, Day 15, 
Day 22, Day 29, and Day 36 of 
Cycles 1-4.
In odd-numbered cycles ≥5 (i.e., 
5, 7, 9, etc.), collected once daily 
on Days 1, 8, 15, 29, and 36.
In even-numbered cycles ≥5 (i.e., 
6, 8, 10, etc.), collected once 
daily on Days 1, 15, 22, and 29.
Additional sampling should be 
performed as clinically indicated.
Chemistry Panel
X1
X2
X
X X X X X X
X X X X X X
X X X X X X
X X X
X
X
X
Prothrombin Time 
(PT)/International 
Normalized Ratio 
(INR) and 
Activated Partial 
Thromboplastin 
Time (aPTT)
X1
Participants on anticoagulant 
therapy should be monitored 
throughout the study.
Lactate 
Dehydrogenase 
(LDH) and Gamma 
Glutamyl 
Transferase (GGT)
X1
X2
X
X
X
X
Collected at screening and prior 
to dosing on Day 1 of each cycle.
Thyroid Function 
Testing
(T4, T3, TSH)
X
X2
X
X
After Cycle 1, samples are 
collected prior to dosing on Day 1 
of every other cycle.
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Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Pregnancy Test 
(urine or serum β-
human chorionic 
gonadotropin [β-
hCG]) - Women of 
childbearing 
potential only
X
X2
Urine pregnancy test to be 
performed as indicated; if test is 
positive or cannot be confirmed 
as negative, a serum pregnancy 
test is required. Monthly testing 
should be conducted per local 
regulations.
HIV/Hepatitis 
Screen
(at the discretion of 
the investigator)
X
Per local regulations.
Urinalysis
X1
Laboratory Procedures/Assessments – CENTRAL
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Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Blood for 
circulating tumor 
DNA (ctDNA) 
Analysis
X
X
X
X
X
X
To be collected predose on Day 1 
of Cycles 1, 2, 4, 7, 10, 13, 16 and
on Day 22 of Cycles 1, 2, 5, 8, 11, 
14, and 17.
Blood for RNA 
Analyses
X
X
X
X
To be collected prior to dosing on 
Day 1 of Cycles 1-4.
Serum for 
Biomarker 
Analyses3
X
X
X
X
X
X
X
To be collected at screening, prior 
to dosing and 2 hours after the 
start of the MK-5890 infusion (±
10 minutes) on Day 1, and once 
on Day 2 of Cycle 1, and prior to 
dosing and 2 hours after the start 
of the MK-5890 infusion (± 10 
minutes) on Day 1 of Cycles 2-6.
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Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Peripheral Blood 
Mononuclear Cell 
(PBMC) Collection 
for Biomarker 
Analyses
X
X
X
X
To be collected prior to dosing on 
Day 1 of Cycles 1-4.
Blood for 
Immunopheno-
typing3
X
X
X
X
X
X
X
X
To be collected at screening prior 
to dosing on Day 1 of Cycles 1-4, 
and on Day 22 of Cycles 1-3.
Blood for Genetic 
Analyses
X
To be collected predose. If there 
is either a documented law or 
regulation prohibiting collection 
of blood for genetic analyses, or 
if the IRB/IEC does not approve 
the collection, sampling will not 
be done at the site. If the planned 
genetic analysis is not approved, 
but FBR is approved and consent 
is given, this sample will be 
collected for the purpose of FBR 
only.
Tumor Tissue 
Collection
X
Required at screening for all 
participants. Newly obtained 
tumor tissue is defined as tissue 
collected within 90 days before
the first dose of study treatment. 
Archival tumor tissue is defined 
as tissue collected more than 90 
days before the first dose of study 
treatment. The actual tumor 
sample is not required to be at the 
study site within the 28-day 
screening period.
PD-L1 testing of 
tumor sample for 
CPS <10
X
PD-L1 IHC 22C3 pharmDx assay 
is required for PD-L1 testing to 
calculate CPS; in the case 22C3 
testing cannot be done locally, 
central testing has to be 
performed
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Study Period
Screening
Treatment Period
Cycle = 42 days
Notes
Visit Timing
Up to 
28 days 
prior to 
1st dose
Cycle 1 
Cycles 2
Cycle 3
Cycle 4
Cycle
≥5
Visit Window (Days) -28 to -1
1
2
3
8
15 22 29 36 1
2
8
15 22 29 36 1
2
8 15 22 29 36 1
2 8 15 22 29
36
Every 
9 
weeks
1/8/15/
22/29/36
Post-Treatment 
Tumor Biopsy
(optional)
X
Requested between Day 8 and 
Day 15 of Cycle 2.
1. Laboratory test at screening are to be performed within 7 days before the first dose of study treatment.
2. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Screening procedures/sample collections done within this timeframe do 
not need to be repeated for the Cycle 1, Day 1 time point.
3. If the sample day falls on a weekend or a holiday, please consult the Sponsor for alternate sample collection times.
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2.7
Schedule of Activities for the End of Treatment and Post-Treatment Follow-Up Periods – Dose Escalation and 
Confirmation Phase and Dose Expansion Phase
Study Period
End of 
Treatment
Post-Treatment Follow-Up
Notes
Safety
Disease 
Status1
Survival2
Visit Timing
Treatment 
discontinuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-14
+/-7
+/-14
Administrative / Clinical Procedures / Assessments
Concomitant Medication
X
X
Physical Examination
X
X
A directed physical examination may be done unless a full examination is deemed 
necessary.
Weight
X
X
Vital Signs
X
X
Measurements include temperature, pulse, respiratory rate, blood pressure.
ECOG Performance Status
X
X
Adverse Event Monitoring
X
X
X
After treatment discontinuation, participants will be monitored for AEs for 
30 days and SAEs for 90 days (30 days if the participant initiates new anticancer 
therapy). Participants with an ongoing AE at the time of treatment discontinuation 
will be followed until resolution, stabilization, the event is otherwise explained, or 
the participant is lost to follow-up.
Tumor Imaging and Response Assessment
X
Post-treatment tumor imaging every 9 weeks starting from the first dose of study 
treatment.
New Anticancer Therapy Status
X
X
X
Survival Status
X
Upon Sponsor request, participants may be contacted for survival status at any 
time during the course of the study. After confirmed disease progression, each 
participant will be contacted by telephone for survival until participant withdrawal 
of consent, becoming lost to follow-up, death, or the end of the study.
Laboratory Procedures/Assessments – LOCAL
Hematology
X
X
Chemistry Panel
X
X
Thyroid Function Testing (T4, T3, TSH)
X
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Study Period
End of 
Treatment
Post-Treatment Follow-Up
Notes
Safety
Disease 
Status1
Survival2
Visit Timing
Treatment 
discontinuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-14
+/-7
+/-14
Laboratory Procedures/Assessments – CENTRAL
Blood for circulating tumor DNA (ctDNA) 
Analysis
X
To be collected at End of Treatment visit.
1. Participants who discontinue study treatment for reasons other than confirmed disease progression will have post-treatment follow-up imaging every 9 weeks for disease 
status until disease progression, initiating a new anticancer therapy, participant withdrawal of consent, pregnancy, becoming lost to follow-up, or death.
2. Participants should be contacted for their first scheduled survival follow-up 12 weeks after the Post-Treatment Safety Follow-Up visit.
3. Arms 3, 1a (anti-MK-5890 antibody and pharmacokinetic sampling for MK-5890 only), 2a, 2b, 2c, and 4 only.
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2.8
Schedule of Activities for the Cross-Over Treatment Phase – Dose Escalation and Confirmation Phase (Arm 1) and 
Dose Expansion Phase (Arm 1a)
Participants who discontinue MK-5890 in the monotherapy arms (Arm 1 and Arm 1a) due to disease progression may, at the 
investigator’s discretion and after consultation with the Sponsor, cross-over to MK-5890 + pembrolizumab combination treatment. 
The list and schedule of procedures to be performed are provided in the following chart.
Study Period /
Treatment Cycle
Treatment Period1, 2, 3
Cycle = 21 days
End of 
Treatment
Post-Treatment Follow-Up Period
Notes
Cycle 1
Cycles ≥2
Safety
Disease 
Status4
Survival5
Visit Timing / Cycle Day
1
8
15
1
Every 9
weeks
Treatment 
dis-
continuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-
2
+/-
3
+/-7
+/-14
+/-7
+/-14
Administrative Procedures
Informed Consent
X
Participants must be re-consented and the risks and benefits of 
continuing treatment after disease progression should be 
reviewed prior to performing any cross-over-related procedures.
Concomitant Medication
X
X
X
X
Clinical Procedures/Assessments
Physical Examination
X6
X6
X
X
A full physical examination should be done at Cycle 1 and at the 
End of Treatment visit. Directed physical examinations may be 
done at the other time points unless a full examination is deemed 
necessary.
Weight
X
X
X
X
Vital Signs
X
X
X
X
Measured prior to dosing, and 2 hours, 4 hours, and 6 hours after 
the start of the MK-5890 infusion on Day 1 of Cycle 1. In 
Cycles ≥2, measured prior to dosing on Day 1 only. Also 
measured at the End of Treatment visit and at the Post-Treatment 
Safety Follow-Up visit.
ECOG Performance Status
X6
X6
X
X
On Day 1, should be performed prior to dosing.
12-Lead Electrocardiogram
X6
X
Performed prior to dosing and within 30 minutes after the end of 
the MK-5890 infusion on Day 1 of Cycles 1-4.
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Study Period /
Treatment Cycle
Treatment Period1, 2, 3
Cycle = 21 days
End of 
Treatment
Post-Treatment Follow-Up Period
Notes
Cycle 1
Cycles ≥2
Safety
Disease 
Status4
Survival5
Visit Timing / Cycle Day
1
8
15
1
Every 9
weeks
Treatment 
dis-
continuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-
2
+/-
3
+/-7
+/-14
+/-7
+/-14
Adverse Event Monitoring
X
X
X
X
X
Continuous AE reporting from the time of treatment allocation. 
After treatment discontinuation, participants will be monitored 
for AEs for 30 days and SAEs for 90 days (30 days if the 
participant initiates new anticancer therapy). Participants with an 
ongoing AE at the time of treatment discontinuation will be 
followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up.
Tumor Imaging and Response 
Assessment
X
X
Every 9 weeks from the first dose of combination treatment.
New Anticancer Therapy Status
X
X
X
Survival Status
X
Upon Sponsor request, participants may be contacted for survival 
status at any time during the course of the study. After confirmed 
disease progression, each participant will be contacted by 
telephone for survival until participant withdrawal of consent, 
becoming lost to follow-up, death, or the end of the study.
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Study Period /
Treatment Cycle
Treatment Period1, 2, 3
Cycle = 21 days
End of 
Treatment
Post-Treatment Follow-Up Period
Notes
Cycle 1
Cycles ≥2
Safety
Disease 
Status4
Survival5
Visit Timing / Cycle Day
1
8
15
1
Every 9
weeks
Treatment 
dis-
continuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-
2
+/-
3
+/-7
+/-14
+/-7
+/-14
Laboratory Procedures/Assessments – LOCAL
Hematology
X6
X
X
X6
X
X
To be collected prior to dosing and 4 hours after the start of the 
MK-5890 infusion on Day 1, and once daily on Day 8 and 
Day 15 of Cycle 1. In Cycles ≥2, to be collected prior to dosing 
on Day 1 only. Samples also to be collected at the End of 
Treatment visit and at the Post-Treatment Safety Follow-Up visit.
Chemistry Panel
X6
X
X
X6
X
X
Lactate Dehydrogenase (LDH) and 
Gamma Glutamyl Transferase 
(GGT)
X6
X6
Thyroid Function Testing
(T4, T3, TSH)
X6
X6
X
To be collected on Day 1 of Cycle 1, every other cycle thereafter, 
and at the Post-Treatment Safety Follow-Up visit.
Laboratory Procedures/Assessments – CENTRAL
Serum for Biomarker Analyses
X
X
MK-5890 infusion on Day 1. 
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Study Period /
Treatment Cycle
Treatment Period1, 2, 3
Cycle = 21 days
End of 
Treatment
Post-Treatment Follow-Up Period
Notes
Cycle 1
Cycles ≥2
Safety
Disease 
Status4
Survival5
Visit Timing / Cycle Day
1
8
15
1
Every 9
weeks
Treatment 
dis-
continuation
30 days 
after the 
last dose
Every 9 
weeks
Every 12 
weeks
Visit Window (Days)
+/-
2
+/-
3
+/-7
+/-14
+/-7
+/-14
Peripheral Blood Mononuclear Cell 
(PBMC) Collection for Biomarker 
Analyses
X
X
X
To be collected prior to dosing on Day 1 of Cycle 1, every 
4 cycles thereafter, and requested at the End of Treatment visit. 
Blood for Immunophenotyping 
X
X
X
To be collected prior to dosing on Day 1 of each cycle, and 
requested at the End of Treatment visit.
Serum for Soluble Receptor 
Analysis
X
X
1. Any participant receiving anticoagulant therapy should have coagulation factors (PT/INR and aPTT) monitored closely throughout the study.
2. For women of childbearing potential, monthly pregnancy testing should be conducted per local regulations where applicable. If a urine pregnancy test is positive or cannot be 
confirmed as negative, a serum pregnancy test is required.
3. Participants will be requested to provide a post-treatment tumor biopsy sample between Day 8 and Day 15 of Cycle 2. Leftover tissue may also be saved for future biomedical 
research (FBR) if the participant signed the FBR consent.
4. Participants who discontinue study treatment for reasons other than confirmed disease progression will have post-treatment follow-up imaging every 9 weeks for disease status 
until disease progression, initiating a new anticancer therapy, participant withdrawal of consent, pregnancy, becoming lost to follow-up, or death.
5. Participants should be contacted for their first scheduled survival follow-up 12 weeks after the Post-Treatment Safety Follow-Up visit.
6. Procedure/sample collection may be performed up to 72 hours before the first dose of study treatment. Procedures/sample collections performed for the End of Treatment visit 
done within this timeframe in the monotherapy arm do not need to be repeated for the cross-over Cycle 1, Day 1 time point.
7. Participants who crossed-over from Arm 1a only.
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3. INTRODUCTION
MK-5890 is a humanized, agonist mAb that binds to the immunomodulatory receptor, CD27, 
providing a co-stimulatory signal that enhances T cell receptor-mediated cellular responses. 
This humanized IgG1 antibody is being developed as a cancer immunotherapeutic with the 
potential to be used as monotherapy or to be combined with pembrolizumab (a humanized 
anti-PD-1 receptor mAb) to increase benefit to patients with various tumor types.
3.1
Study Rationale
MK-5890 is being developed for the treatment of solid tumors. This is the first-in-human 
study of MK-5890 and is designed to assess the safety, tolerability, PK, and PD of escalating 
doses of MK-5890 when used as monotherapy and in combination with pembrolizumab in 
participants with advanced solid tumors who have received or been intolerant to all treatment 
known to confer clinical benefit. The effect of MK-5890 on tumor size will also be explored.
In addition, the Arm 3 cohort in the dose escalation/dose confirmation phase of the study will 
assess the safety and tolerability of treatment with MK-5890 in combination with 
pembrolizumab and standard chemotherapy in participants with nonsquamous NSCLC.
The dose expansion phase of the study will further examine safety and exploratory efficacy 
of MK-5890 when used as monotherapy and in combination with pembrolizumab in specific 
tumor types as described in Inclusion Criterion 1 (Section 6.1).
In addition, the Arm 4 cohort in the dose expansion phase of the study will assess the safety 
and tolerability and efficacy of treatment with MK-5890 in combination with pembrolizumab 
and standard chemotherapy in participants with locally recurrent inoperable TNBC cancer 
not previously treated with chemotherapy and which cannot be treated with curative intent or 
with  previously not treated metastatic TNBC whose tumor PD-L1 CPS is less than 10.
3.2
Background
Refer to the Investigator’s Brochures (IBs) for detailed background information on MK-5890
and pembrolizumab.
3.2.1
Pharmaceutical and Therapeutic Background
3.2.1.1
MK-5890 Background
MK-5890 is a CD27 agonist antibody being developed as a novel cancer immunotherapeutic 
agent with an initial focus to increase benefit to patients with treatment-refractory 
malignancies. CD27 is a co-stimulatory member of the TNF receptor superfamily, which is 
constitutively expressed on naïve, activated and memory T cells, NK T cells, memory 
B cells, and a subset of NK cells [Nolte, M. A., et al 2009] [Borst, J., et al 2005] [Lens, S. 
M., et al 1998]. CD27 signaling is regulated through strict control of expression of its ligand, 
CD70, which is transiently expressed on activated T and B cells, primed dendritic cells, 
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NK cells, and dendritic and epithelial cells of the thymic medulla [Nolte, M. A., et al 2009] 
[Coquet, J. M., et al 2013] [Hishima, T., et al 2000] [Kashii, Y., et al 1999] [Orengo, A. M., 
et al 1997].
CD27 signaling plays an important role in both generation and maintenance of cytotoxic 
T lymphocyte responses and in survival of activated T cells after they traffic to non-lymphoid 
organs (Figure 1). Given that CD27 signaling enhances priming of cytotoxic T lymphocyte
responses even in the absence of primed antigen presenting cells [Ahrends, T., et al 2016],
the CD27 agonistic activity can be exploited as an immunotherapeutic approach for cancers 
with minimal T cell infiltrate and/or inadequate responses. In combination with anti-PD-1 or 
other immune checkpoint inhibitors, CD27 signaling can be used to protect newly generated 
T cells in the tumor. This rationale has been supported by pre-clinical data from human 
CD27 knock-in mouse model syngeneic tumor studies showing efficacy of MK-5890 as both 
a monotherapy and in combination with anti-PD-1.
Figure 1
Mechanism of Action of the CD27/CD70 Co-Stimulatory System in Regulation of 
the T Cell Response
Adapted from van de Ven and Borst 2015 [van de Ven, K. 2015]
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3.2.1.2
Pembrolizumab (MK-3475) Background
Pembrolizumab is a potent humanized IgG4 mAb with high specificity of binding to the 
PD-1 receptor, thus inhibiting its interaction with PD-L1 PD-L2). Based on preclinical 
in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD-1.
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress 
immune control. The normal function of PD-1, expressed on the cell surface of activated 
T cells under healthy conditions, is to down-modulate unwanted or excessive immune 
responses, including autoimmune reactions. PD-1 (encoded by the gene Pdcd1) is an Ig 
superfamily member related to cluster of differentiation 28 (CD28) and cytotoxic 
T lymphocyte-associated protein 4 (CTLA-4) that has been shown to negatively regulate 
antigen receptor signaling upon engagement of its ligands (PD-L1 and/or PD-L2) 
[Greenwald, R. J., et al 2005] [Okazaki, T., et al 2001].
The structure of murine PD-1 has been resolved [Zhang, X., et al 2004]. PD-1 and its family 
members are Type I transmembrane glycoproteins containing an Ig variable-type (IgV-type) 
domain responsible for ligand binding and a cytoplasmic tail responsible for the binding of 
signaling molecules. The cytoplasmic tail of PD-1 contains 2 tyrosine-based signaling motifs, 
an immunoreceptor tyrosine-based inhibition motif, and an immunoreceptor tyrosine-based 
switch motif. Following T cell stimulation, PD-1 recruits the tyrosine phosphatases, SHP-1 
and SHP-2, to the immunoreceptor tyrosine-based switch motif within its cytoplasmic tail, 
leading to the dephosphorylation of effector molecules such as CD3 zeta (CD3ζ), protein 
kinase C-theta (PKCθ), and zeta-chain-associated protein kinase (ZAP70), which are 
involved in the CD3 T cell signaling cascade [Okazaki, T., et al 2001] [Chemnitz, J. M., et al 
2004] [Sheppard, K-A, et al 2004] [Riley, J. L. 2009]. The mechanism by which PD-1 
down-modulates T cell responses is similar to, but distinct from that of CTLA-4 because both 
molecules regulate an overlapping set of signaling proteins [Parry, R. V., et al 2005] 
[Francisco, L. M., et al 2010]. As a consequence, the PD-1/PD-L1 pathway is an attractive 
target for therapeutic intervention in a variety of cancers.
3.2.2
Pre-Clinical and Clinical Studies
3.2.2.1
MK-5890 Pre-Clinical and Clinical Studies
Pre-clinical studies of MK-5890 are described in the IB. This is the first clinical study of 
MK-5890.
3.2.2.2
Pembrolizumab (MK-3475) Pre-Clinical and Clinical Studies
Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as 
an intravenous (IV) immunotherapy, both as monotherapy and combination therapy, for 
advanced malignancies. Keytruda™ (pembrolizumab) is indicated for the treatment of 
patients across a number of indications. For more details on specific indications, refer to the 
IB and Physician Circular.
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3.2.3
Ongoing Clinical Studies
3.2.3.1
MK-5890 Ongoing Clinical Studies
This study represents the first-in-human use of MK-5890.
3.2.3.2
Pembrolizumab Ongoing Clinical Studies
Over 400 interventional clinical studies involving pembrolizumab are currently ongoing in a 
number of advanced solid tumor indications, as well as in hematological malignancies.
3.2.4
Information on Other Study-Related Therapy
Participants with nonsquamous NSCLC enrolled as part of Amendment 02 will receive 
concomitant chemotherapy with pemetrexed and carboplatin as per their product labels. 
Refer to their respective package inserts for more information.
Participants with locally recurrent inoperable TNBC not previously treated with 
chemotherapy and which cannot be treated with curative intent or with previously not treated 
metastatic TNBC whose tumor PD-L1 CPS is less than 10 enrolled as part of Amendment 03
will receive concomitant chemotherapy with nab-paclitaxel as per its product labels. Refer to 
its respective package inserts for more information.
3.3
Benefit/Risk Assessment
It cannot be guaranteed that participants in clinical studies will directly benefit from 
treatment during participation, as clinical studies are designed to provide information about 
the safety and effectiveness of an investigational medicine.
Additional details regarding specific benefits and risks for participants participating in this 
clinical study may be found in the accompanying IB and informed consent documents.
4. OBJECTIVES/HYPOTHESES AND ENDPOINTS
In male and female participants with advanced solid tumors who are at least 18 years of age:
Objectives
Endpoints
Primary

Objective: To determine the safety and 
tolerability and to establish a preliminary 
recommended Phase 2 dose (RP2D) of 
MK-5890 when used as monotherapy and 
in combination with pembrolizumab in 
the dose escalation and confirmation 
phase and the dose expansion phase

Number of participants with a 
dose-limiting toxicity (DLT)

Number of participants with ≥1 
adverse event (AE)

Number of participants who 
discontinue study treatment due to an 
AE
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Objectives
Endpoints
Secondary

Objective: To evaluate the PK of 
MK-5890 when given by IV infusion as 
monotherapy, in combination with 
pembrolizumab, in combination with 
pembrolizumab, pemetrexed, and 
carboplatin, and in combination with 
pembrolizumab and nab-paclitaxel, in the 
dose escalation and confirmation phase 
and/or the dose expansion phase

PK parameters including area under the 
curve (AUC), minimum concentration 
(Cmin), and maximum concentration 
(Cmax)

Objective: To evaluate the objective 
response rate (ORR) of MK-5890 when 
used as monotherapy, in combination 
with pembrolizumab, in combination 
with pembrolizumab and nab-paclitaxel
in the dose expansion phase

ORR as assessed by the investigator 
based on Response Evaluation Criteria 
in Solid Tumors, version 1.1 
(RECIST 1.1)

Objective: To determine the safety and 
tolerability of MK-5890 in combination 
with pembrolizumab, pemetrexed, and 
carboplatin in participants with 
nonsquamous NSCLC and to establish 
maximum tolerated doses (MTDs) of 
carboplatin and pemetrexed when used in 
combination with MK-5890 and 
pembrolizumab

Number of participants with a DLT

Number of participants with ≥1 AE

Number of participants who 
discontinue study treatment due to an 
AE

Objective: To determine the safety and 
tolerability of MK-5890 in combination 
with pembrolizumab and nab-paclitaxel
in participants with locally recurrent 
inoperable TNBC cancer not previously 
treated with chemotherapy and which 
cannot be treated with curative intent or 
with  previously not treated metastatic 
TNBC and to establish MTDs of nab-
paclitaxel when used in combination 
with MK-5890 and pembrolizumab

Number of participants with a DLT

Number of participants with ≥1 AE

Number of participants who 
discontinue study treatment due to an 
AE
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Objectives
Endpoints
Tertiary/Exploratory

Objective: To evaluate the preliminary 
antitumor activity of MK-5890 when 
used as monotherapy, in combination 
with pembrolizumab, and in combination 
with pembrolizumab, pemetrexed, and 
carboplatin in the dose escalation and 
confirmation phase

ORR and progression-free survival
(PFS) as assessed by the investigator 
based on RECIST 1.1 and modified 
RECIST 1.1 for immune-based 
therapeutics (iRECIST) [Seymour, L., 
et al 2017], and overall survival (OS)

Objective: To evaluate the antitumor 
activity of MK-5890 when used as 
monotherapy, in combination with 
pembrolizumab, in combination with 
pembrolizumab and nab-paclitaxel, in the 
dose expansion phase

ORR as assessed by the investigator 
based on iRECIST, and PFS as 
assessed by the investigator based on 
RECIST 1.1 and iRECIST, and OS

Objective: To evaluate development of 
circulating anti-MK-5890 antibodies and 
anti-pembrolizumab antibodies, as 
appropriate, following administration of 
MK-5890 monotherapy, MK-5890 in 
combination with pembrolizumab, in 
combination with pembrolizumab and 
nab-paclitaxel, and MK-5890 in 
combination with pembrolizumab, 
pemetrexed, and carboplatin, in the dose 
escalation and confirmation phase and/or 
the dose expansion phase

Circulating anti-MK-5890 and 
anti-pembrolizumab antibody levels

Objective: To evaluate the PK of
pembrolizumab when used in 
combination with MK-5890, the PK of 
pembrolizumab, pemetrexed, and 
carboplatin when used in combination 
with MK-5890, and the PK of 
pembrolizumab when used in 
combination with MK-5890 with nab-
paclitaxel in the dose escalation and 
confirmation phase and/or the dose 
expansion phase

PK parameters including AUC, Cmin, 
and Cmax
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Objectives
Endpoints
5. STUDY DESIGN
5.1
Overall Design
This is a first-in-human, multi-site, open-label, dose escalation, dose confirmation, and dose 
expansion study of MK-5890 when used as monotherapy and/or in combination with 
pembrolizumab in participants with a histologically or cytologically confirmed diagnosis of 
advanced solid tumor who have received or been intolerant to all treatment known to confer 
clinical benefit. The study will include 2 parts: a dose escalation and confirmation phase 
(Section 5.5.6) and a dose expansion phase to further examine safety and exploratory 
efficacy of MK-5890 when used as monotherapy and in combination with pembrolizumab 
and chemotherapy in specific tumor types (Section 5.5.7).
The dose escalation and confirmation phase of the study will use a mTPI design [Ji, Y., et al 
2007] with a target DLT rate of 30% to identify a preliminary RP2D of MK-5890 when used 
as monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2). Participants will 
be allocated by non-random assignment to a treatment arm using an interactive voice 
response system/integrated web response system (IVRS/IWRS). Study treatment will be 
administered by IV infusion on Day 1 of each 21-day cycle for up to a maximum of 
35 cycles.
Six pre-determined dose levels of MK-5890 will be explored independently in each treatment 
arm. It may be acceptable to de-escalate to an intermediate dose that was not predefined and 
not previously studied if evaluation of toxicity at such a dose is desired. The dose of 
pembrolizumab in Arm 2 will remain constant at 200 mg. There will be no intraparticipant
dose escalation for participants enrolled in this study except as described in Section 7.2.3.
Enrollment into the MK-5890 + pembrolizumab combination treatment arm (Arm 2) will 
begin once all participants at the second dose level in the MK-5890 monotherapy arm 
(Arm 1) complete the DLT evaluation period and a dose escalation decision has been made. 
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When both treatment arms are open for enrollment, IVRS/IWRS will alternate participant 
assignment between Arms 1 and 2 starting with Arm 1. An observation period of at least 24 
hours will occur between treatment initiation in the first 3 participants enrolled within each 
dose level. Each new dose cohort will open for enrollment without delay once the 21-day 
DLT evaluation period of the previous dose cohort is completed and a dose escalation 
decision has been made.
During dose escalation, a minimum of 3 participants are required at each dose, and up to 
6 participants may be enrolled initially at each new dose. As outlined in Table 4, based on the 
mTPI design, the number of participants who are enrolled at a dose but are not yet fully 
evaluable for DLT assessment may not exceed the number of remaining participants who are 
at risk of developing a DLT before the dose would be considered unacceptably toxic.
Dose escalation and confirmation will end after 14 participants have been treated at any of 
the selected doses (including intermediate doses) as long as the decision based on Table 4 is 
to stay. The pool-adjacent-violators algorithm [Ji, Y. and Wang, S.-J. 2013] will be used to 
estimate the DLT rates across doses in each treatment arm under the assumption of 
monotonicity between DLT rates and dose levels. The dose with an estimated DLT rate 
closest to 30% may be treated as a preliminary RP2D, however, the totality of the data will 
also be considered. The preliminary RP2D of MK-5890 in the combination arm (Arm 2) will 
not exceed, but may equal, the preliminary RP2D in the MK-5890 monotherapy arm 
(Arm 1).
In addition to testing MK-5890 as monotherapy and combination treatment with 
pembrolizumab in participants with advanced solid tumors, the dose escalation and 
confirmation phase will also include a cohort of participants with nonsquamous NSCLC who 
will be treated with 
MK-5890 in combination with 200 mg pembrolizumab, 
500 mg/m2 pemetrexed, and AUC 5 mg/mL/min carboplatin for up to 4 cycles followed by 
maintenance therapy with MK-5890, pembrolizumab, and pemetrexed (Arm 3). MK-5890 
will be given for up to a total of 6 months. Pembrolizumab and pemetrexed will be given for 
up to a total of 35 cycles with the possibility of continuing pemetrexed during the follow-up 
phase of the study at the discretion of the investigator per standard of care. All treatments 
will be given by IV infusion once every 3 weeks (Q3W). For participants who continue 
pemetrexed after 35 cycles, pemetrexed will not be considered a new anticancer therapy. In 
the event of unacceptable toxicity during the chemotherapy combination, the doses of 
chemotherapy will be de-escalated according to the rules outlined in the mTPI design 
(Table 4). The chemotherapy doses that will be tested are outlined in Table 3. Dose finding 
will end after 10 participants have been treated at a dose level of the chemotherapy 
combination as long as the decision based on Table 4 is to stay or escalate. Arm 3 may stop 
early if the number of DLTs exceeds an acceptable rate while at the lowest possible dose 
combination.
The dose expansion phase will assess the safety and antitumor efficacy of 
 MK-5890 in 
combination with 200 mg pembrolizumab, both given Q3W in 15 to 30 participants with 
triple-negative breast cancer (TNBC; [Arm 2a]) using an adaptive design. In the adaptive 
design, the totality of the data will be examined once the first 15 participants with TNBC are 
enrolled and have at least 1 post-baseline scan to decide whether or not to continue 
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enrollment to 30 participants. 
 
.
Enrollment will not be held after the first 15 participants; data will be analyzed on an 
ongoing basis.
The dose expansion phase will also assess the safety and antitumor efficacy of 
 
MK-5890 given Q3W as monotherapy (Arm 1a), 30 mg MK-5890 in combination with 
200 mg pembrolizumab, both given Q3W (Arm 2b), and 30 mg MK-5890 in combination 
with 400 mg pembrolizumab, both given once every 6 weeks (Q6W; Arm 2c) in 
60 participants with endometrial cancer (20 participants per arm) using an adaptive design. 
Participants with endometrial cancer will be randomized at a 1:1:1 ratio to an arm using 
IVRS/IWRS. In the adaptive design, the totality of the data will be examined once the first 
10 participants with endometrial cancer per treatment arm are enrolled and have at least 
1 post-baseline scan to decide whether or not to continue enrollment to 20 participants in that 
arm.
 
 
Enrollment will not be held after the first 10 participants per treatment arm; data will be 
analyzed on an ongoing basis.
In addition, the dose expansion phase will assess the safety and antitumor efficacy of 
 
MK-5890 in combination with 400 mg pembrolizumab and 100 mg/m2 nab-paclitaxel; MK-
5890 and pembrolizumab given Q6W up to 18 cycles (approximately 2 years) and nab-
paclitaxel will be administered on a 3-week on (Days 1, 8, and 15)/1-week off schedule every 
28 days (Arm 4), in participants with locally recurrent inoperable TNBC not previously 
treated with chemotherapy and which cannot be treated with curative intent or with
previously not treated metastatic TNBC whose tumor PD-L1 CPS is less than 10. This cohort 
will first evaluate the safety with 10 participants. In the event of unacceptable toxicity, the 
doses of nab-paclitaxel will be de-escalated according to the rules outlined in the mTPI 
design (Table 4). The nab-paclitaxel doses that will be tested are outlined in Table 3. Dose 
finding will end after 10 participants have been treated at a dose level of the chemotherapy 
combination as long as the decision based on Table 4 is to stay or escalate. Arm 4 may stop 
early if the number of DLTs exceeds an acceptable rate while at the lowest possible dose 
combination. After Arm 4 has demonstrated a tolerable safety profile, additional 30 
participants will be enrolled at the tolerable dose level for further efficacy evaluation. In the 
adaptive design, the totality of the data will be examined once the first 20 participants at the 
tolerable dose level are enrolled (including the 10 participants for safety evaluation) and have 
at least 1 post-baseline scan to decide whether or not to continue enrollment to 
40 participants in Arm 4.
 
 
 
Enrollment will not be held after the first 20 participants enrolled; data 
will be analyzed on an ongoing basis.
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In Arm 1a, MK-5890 will be given for up to 35 cycles. In Arms 2a and 2b, MK-5890 will be 
given for up to 6 months and pembrolizumab will be given for up to 35 cycles. In Arm 2c
and Arm 4, MK-5890 and pembrolizumab will be given for up to 18 cycles.
The doses/schedules of MK-5890 to be tested in the dose expansion phase were determined 
using the totality of the available data from the dose escalation and confirmation phase.
The Sponsor may prematurely terminate enrollment into a tumor type for administrative 
reasons; in such cases, the sites will be notified via an administrative letter. All participants 
already enrolled or in the screening period will be allowed to continue in the study.
Participants in all phases of the study will receive study treatment until disease progression, 
unacceptable AE(s), intercurrent illness that prevents further administration of treatment, 
investigator’s decision to withdraw treatment, participant withdrawal of consent, pregnancy 
of the participant, noncompliance with study treatment or procedure requirements, the 
participant completes study treatment (see Section 8.1 for details), administrative reasons 
requiring cessation of treatment, or death, whichever occurs first.
Participants in the dose escalation and confirmation and dose expansion phases of the study 
who discontinue MK-5890 in the monotherapy arm due to disease progression may, at the 
investigator’s discretion and after consultation with the Sponsor, cross-over to
MK-5890 + pembrolizumab combination treatment (Section 7.2.3).
After treatment discontinuation, participants will be monitored for AEs for 30 days and 
serious adverse events (SAEs) for 90 days (30 days if the participant initiates new anticancer 
therapy). Participants with an ongoing AE at the time of treatment discontinuation will be 
followed until resolution, stabilization, the event is otherwise explained, or the participant is 
lost to follow-up.
Participants who discontinue study treatment for reasons other than confirmed disease 
progression will have post-treatment follow-up imaging every 9 weeks for disease status until 
disease progression, initiating a new anticancer therapy, participant withdrawal of consent, 
pregnancy, becoming lost to follow-up, or death, whichever occurs first.
After confirmed disease progression, each participant will be contacted by telephone 
approximately every 12 weeks for survival until participant withdrawal of consent, becoming 
lost to follow-up, death, or the end of the study, whichever occurs first.
Final RP2D(s) for MK-5890 will be determined using PK and PD endpoints, as well as all 
available safety data, including DLT rates and the cumulative incidence of late toxicities (ie, 
toxicities that occur after the 21-day DLT evaluation period) from participants in all phases 
of the study.
The study will be conducted in conformance with Good Clinical Practice (GCP). Adverse 
events will be evaluated according to criteria outlined in the National Cancer Institute’s 
(NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 or later.
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Specific procedures to be performed during the study, as well as their prescribed times and 
associated visit windows, are outlined in the Study SoA - Section 2. Details of each 
procedure are provided in Section 9 – Study Assessments and Procedures.
5.1.1
Study Diagram
The study design is depicted in Figure 2.
Figure 2
Study Design 
Dose Escalation and Confirmation Phase
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Dose Expansion Phase
IV=intravenous; mTPI=modified toxicity probability interval; ORR=objective response rate; 
RP2D=recommended Phase 2 dose; Q3W=once every 3 weeks; Q6W=once every 6 weeks; TNBC=triple 
negative breast cancer
5.2
Number of Participants
This study is expected to enroll approximately 202 participants.  
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5.3
Beginning and End of Study Definition
The overall study begins when the first participant (or their legally acceptable representative) 
provides documented informed consent. The overall study ends when the last participant 
completes the last study-related contact, withdraws consent, or is lost to follow-up (ie, the 
participant is unable to be contacted by the investigator).
5.3.1
Clinical Criteria for Early Study Termination
Early study termination will be the result of the criteria specified below:
1. The incidence or severity of adverse drug reactions in this, or other, studies suggest a 
potential health hazard to participants;
2. Plans emerge to modify or discontinue the development of the study drug;
3. There is poor adherence to the protocol and/or regulatory requirements; and/or
4. The quality or quantity of data recording is inaccurate or incomplete.
Ample notification will be provided to the sites if the Sponsor decides not to continue to 
supply MK-5890 and/or pembrolizumab.
5.4
Scientific Rationale for Study Design
MK-5890 is being developed for the treatment of solid tumors. This is the first-in-human 
study of this antibody and is designed to assess the safety, tolerability, PK, and PD of 
escalating doses of MK-5890 when used as monotherapy and in combination with 
pembrolizumab in participants with advanced/refractory solid tumors. The effect of 
MK-5890 on tumor size will also be explored. The anti-CD27 agonistic activity of MK-5890 
has been studied in syngeneic mouse tumor models. Administration of this antibody was 
associated with regression of established solid tumors and systemic immune response. 
Preclinical efficacy data demonstrated that the combination of anti-CD27 and anti-PD-1 
antibodies resulted in improved antitumor efficacy. For detailed data from the pre-clinical 
studies, please refer to the IB.
Selection of particular tumor types for the dose expansion phase of the study was based on 
multiple factors including all available clinical and preclinical data, the current therapeutic 
landscape, and the unmet medical need for more efficacious therapies. TNBC represents a 
tumor with high inflammatory phenotype but at the same time low response rate for therapy 
with immune checkpoint inhibitors. Given the mechanism of action of MK-5890, stimulation 
of tumor residing T cells can potentially energize antitumor activity when combined with 
immune checkpoint inhibitors. The early efficacy signal observed in endometrial cancer in 
the MK-5890 monotherapy arm of the dose escalation and confirmation phase helped select 
this tumor type for expansion.
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Addition of Chemotherapy to MK-5890 Plus Pembrolizumab Combination
The Arm 3 cohort in the dose escalation/dose confirmation phase of the study will assess the 
safety and tolerability of treatment with MK-5890 in combination with pembrolizumab and 
standard chemotherapy in participants with non-squamous NSCLC. 
The Arm 4 cohort will test safety/tolerability and antitumor activity of MK-5890 in 
combination with pembrolizumab and nab-paclitaxel in participants with locally recurrent 
inoperable TNBC not previously treated with chemotherapy and which cannot be treated 
with curative intent or with previously not treated metastatic TNBC whose tumor PD-L1 
CPS is less than 10.
Preclinical and clinical evidence suggest that conventional chemotherapies reactivate 
antitumor immune responses by increasing immunogenic cell death and antigen release, 
and/or by inhibiting immunosuppressive factors in the tumor microenvironment [Emens, L. 
A. and Middleton, G. 2015] [Galluzzi, L., et al 2015] [Vincent, J., et al 2010]. Further, 
chemotherapies can enhance tumor antigen presentation by upregulating the expression of 
either tumor T cell receptors (TCRs) themselves, or the MHC1 molecules to which the TCRs 
bind [Emens, L. A. and Middleton, G. 2015]. A substantial body of clinical evidence has 
emerged to suggest that the efficacy of immunotherapy, including PD-1 blockade with 
pembrolizumab, can be enhanced by chemotherapy [Langer, C. J., et al 2016] [Gandhi, L., et 
al 2018]. There is no clinical data for the combination of MK-5890 or other anti-CD27
antibodies with chemotherapeutic agents to date. This study will test the safety and 
tolerability of MK-5890 plus pembrolizumab in combination with pemetrexed and 
carboplatin in patients with non-squamous NSCLC or in combination with nab-paclitaxel in 
participants with locally recurrent inoperable TNBC not previously treated with 
chemotherapy and which cannot be treated with curative intent or with previously not treated
metastatic TNBC whose tumor PD-L1 CPS is less than 10. In the event of unacceptable 
toxicity during the chemotherapy combination, the doses of chemotherapy will be 
de-escalated according to the rules outlined in the mTPI design using the standard dose 
modification guidelines for these regimens. The rationale for de-escalating the doses of 
chemotherapies is that maximum doses of chemotherapeutic agents are defined by MTDs, 
with doses limited by the rate of DLTs. Biologics are not typically MTD-limited. In this 
study, DLTs have been observed in association with infusion-related reactions, but not with 
other adverse events during dose escalation, whether alone or in combination with 
pembrolizumab. In an attempt to manage occurrence of infusion-related reactions, a 
recommendation to premedicate participants was made. If the triple combination is tolerable 
and doses of chemotherapy are determined, the safety and efficacy of this triple combination 
in patients with NSCLC and TNBC may be further evaluated in a separate study. The overall 
intention is to determine whether addition of MK-5890 to pembrolizumab and chemotherapy 
provides superior efficacy benefit to combination of immune checkpoint inhibitor and 
chemotherapy, which is a current standard of care treatment for patients with untreated 
advanced NSCLC of nonsquamous histology and TNBC.
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5.4.1
Rationale for Endpoints
5.4.1.1
Efficacy Endpoints
Efficacy endpoints include ORR, PFS, and OS and are secondary and tertiary/exploratory 
endpoints in this study. Tumor response will be assessed by investigators using RECIST 1.1
and iRECIST.
Immune-modified RECIST 1.1 for immune-based therapeutics [Seymour, L., et al 2017]
accounts for the unique tumor response characteristics seen with immunotherapeutic agents. 
iRECIST was developed and published by the RECIST Working Group, with input from 
leading experts from industry and academia, along with participation from the US Food and 
Drug Administration and the European Medicines Agency.
Immunotherapeutic agents such as MK-5890 and pembrolizumab may produce antitumor 
effects by potentiating endogenous cancer-specific immune responses. The response patterns 
seen with such an approach may extend beyond the typical time course of responses seen 
with cytotoxic agents, and can manifest a clinical response after an initial increase in tumor 
burden or even the appearance of new lesions. Standard RECIST may, thus, not provide an 
accurate response assessment of immunotherapeutic agents. These findings support the need 
to apply a modification to RECIST 1.1 that takes into account the unique patterns of atypical 
response in immunotherapy and enables treatment beyond initial radiographic progression, if 
the participant is clinically stable.
The unidimensional measurement of target lesions, qualitative assessment of non-target 
lesions, and response categories are identical to RECIST 1.1, until progression is seen by 
RECIST 1.1. If a participant is clinically stable, additional imaging may be performed to 
confirm radiographic progression. In this study, iRECIST will be used by investigators to 
assess tumor response and progression, and make treatment decisions.
5.4.1.2
Safety Endpoints
The primary objectives of this study include characterizing the safety and tolerability of 
MK-5890 when used as monotherapy and in combination with pembrolizumab in 
participants with advanced solid tumors. Secondary objectives include determining the safety 
and tolerability of MK-5890 in combination with pembrolizumab, pemetrexed, and 
carboplatin in participants with nonsquamous NSCLC. The secondary objectives also include 
determining the safety and tolerability of MK-5890 in combination with pembrolizumab and 
nab-paclitaxel in participants with locally recurrent inoperable TNBC not previously treated 
with chemotherapy and which cannot be treated with curative intent or with previously not 
treated metastatic TNBC whose tumor PD-L1 CPS is less than 10.  
The primary safety analyses will be based on the number of participants who experience 
toxicities as defined by the NCI CTCAE, version 4.0 or later.
The attribution to study treatment, time of onset, duration of the event, resolution of the 
event, and any concomitant medications administered as a result of the event will be 
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recorded. Safety data will include, but are not limited to, AEs, SAEs, fatal AEs, and 
laboratory changes. Furthermore, specific events will be collected and designated as events 
of clinical interest (ECIs) as described in Section 9.3.7.
5.4.1.3
5.4.1.4
5.4.1.5
5.4.1.6
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5.4.1.6.1
5.4.1.6.2
5.4.1.6.3
5.4.1.6.4
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5.4.1.6.5
5.4.1.6.6
e 
5.4.2
Rationale for The Use of Comparator/Placebo
No comparator/placebo is proposed for this study.
5.5
Justification for Dose
5.5.1
C
C
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5.5.2
5.5.3
5.5.3.1
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5.5.3.2
Pembrolizumab (MK-3475)
The planned dose of pembrolizumab for Arms 2, 3, 2a, and 2b of this study is 200 mg given 
Q3W. Based on the totality of data generated in the Keytruda development program, 200 mg 
given Q3W is the appropriate dose of pembrolizumab for adults across all indications and 
regardless of tumor type.
In Arms 2c and 4, pembrolizumab will be given at a dose of 400 mg Q6W. Based on the 
robust understanding of pembrolizumab clinical pharmacology, including well-established 
exposure-response profiles over a 5-fold dose range (dataset of 2993 participants), a 400 mg 
Q6W dosing regimen is expected to produce similar efficacy and safety in all clinical 
treatment settings where 200 mg (or 2 mg/kg) Q3W pembrolizumab dosing is currently 
approved.
5.5.4
Rationale for Pemetrexed and Carboplatin Doses in NSCLC
The starting doses of chemotherapies in this study: 500 mg/m2 pemetrexed and 
AUC 5 mg/mL/min carboplatin, both administered by IV infusion Q3W for up to 4 cycles,
with the possibility of maintenance therapy with pemetrexed at the discretion of the 
investigator, represent the standard of care per the approved product labels.
5.5.5
Rationale for Nab-paclitaxel Doses in Previously Untreated Metastatic TNBC
Nab-paclitaxel is a combination of albumin and paclitaxel that forms particles of a mean 130 
nm in diameter. Unlike previous taxanes, the nab-paclitaxel formulation is solvent-free and 
does not require premedication to prevent solvent-related hypersensitivity reactions. It 
received US FDA approval in 2005 for the treatment of breast cancer after failure of 
combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant 
chemotherapy (prior therapy should have included an anthracycline, unless clinically 
contraindicated). Nab-paclitaxel is also approved in the EU as 2L monotherapy for mBC. 
These approvals were based on a randomized Phase 3 study, which compared nab-paclitaxel 
260 mg/m2 Q3W to paclitaxel 175 mg/m2 Q3W with corticosteroid or antihistamine 
premedication [Gradishar, W. J., et al 2005]. Treatment with nab-paclitaxel led to a 
significantly higher ORR compared with paclitaxel based on the ITT population (33% versus
19%, respectively; p = 0.001). The ORR was also significantly higher in participants who 
received nab-paclitaxel as 1L therapy (42% versus 27%; p = 0.029) or 2L and above (2L+) 
therapy (27% versus 13%; p = 0.006). Participants who received nab-paclitaxel had a 25% 
lower risk of progression compared with those receiving paclitaxel (HR 0.75; p = 0.006). The 
incidence of Grade 4 neutropenia was significantly lower with nab-paclitaxel treatment (9% 
versus 22%, respectively; p < 0.001). Nab-paclitaxel was associated with higher incidence of
Grade 3 sensory neuropathy (10% versus 2%; p < 0.001), which improved to ≤Grade 2 in 
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about 3 weeks. Nab-paclitaxel demonstrated a statistically significant improvement in OS in 
participants who received it as 2L+ therapy (56.4 versus 46.7 weeks; p = 0.024), but only a 
modest, nonsignificant OS difference in the ITT population (65 versus 56 weeks; p = 0.374). 
In addition, nab-paclitaxel has been approved in combination with  1) atezolizumab (PD-L1 
inhibitor) for treatment of PD-L1 positive unresectable locally advanced or metastatic TNBC
[Kang, C. and Syed, Y. Y. 2020]; 2) pembrolizumab for treatment of locally recurrent 
unresectable or metastatic TNBC whose tumors express PD-L1 with CPS ≥10 [U.S. 
Prescribing Information 2020].  
The starting dose of chemotherapy in Arm 4: 100 mg/m2 nab-paclitaxel, administered by IV 
infusion administered on a 3-week on (Days 1, 8 and 15)/1-week off schedule every 28 days,
represent the standard of care per the approved product labels.
If the mTPI design calls for a de-escalation, the doses of pemetrexed and carboplatin, and 
nab-paclitaxel will be reduced as outlined in Table 3.
Table 3
Chemotherapy Dose Level Definitions
Dose Level 0
Dose Level -1
Dose Level -2
Dose Level -3
Carboplatin
AUC 5 mg/mL/min
Maximum dose 
750 mg
AUC 3.75 
mg/mL/min
Maximum dose 
562.5 mg
AUC 2.5 
mg/mL/min
Maximum dose 
375 mg
Discontinue 
treatment
Pemetrexed
500 mg/m2
375 mg/m2
250 mg/m2
Discontinue 
treatment
Nab-paclitaxel
100 mg/m2
80 mg/m2
64 mg/m2
Discontinue 
treatment
AUC=area under the curve
Dose levels of pemetrexed, carboplatin and nab-paclitaxel below Dose Level -2 will not be 
explored. If the mTPI design calls for an additional de-escalation, enrollment into Arm 3 
and/or Arm 4 will be closed. Arms 3 and/or 4 may stop early if the number of DLTs exceeds 
an acceptable rate while at the lowest possible dose combination
5.5.6
Dose Finding Using a Modified Toxicity Probability Interval Design
During dose escalation and confirmation, an mTPI design [Ji, Y., et al 2007] with a target 
DLT rate of 30% will be applied to identify a preliminary RP2D of MK-5890 when used as
monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2) according to the 
rules outlined in Table 4.
Six pre-determined dose levels of MK-5890 will be explored independently in each arm: 
2 mg, 7 mg, 20 mg, 70 mg, 200 mg and 700 mg. It may be acceptable to de-escalate to an 
intermediate dose that was not predefined and not previously studied if evaluation of toxicity 
at such a dose is desired. All dose escalation decisions will be based on the occurrence of 
DLTs and will be made jointly by the investigators and the Sponsor. The dose of 
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pembrolizumab in Arm 2 will remain constant at 200 mg. Study treatment will be 
administered Q3W. There will be no intraparticipant dose escalation for participants enrolled 
in this study except as described in Section 7.2.3.
Treatment will be allocated by non-random assignment. Enrollment into the 
MK-5890 + pembrolizumab combination treatment arm (Arm 2) will begin once all 
participants at the second dose level in the MK-5890 monotherapy arm (Arm 1) complete the 
DLT evaluation period and a dose escalation decision has been made. This ensures that the 
starting dose of MK-5890 in the combination arm will be at least 2 levels below the dose 
being tested in the MK-5890 monotherapy arm. When both treatment arms are open for 
enrollment, IVRS/IWRS will alternate participant assignment between Arms 1 and 2 starting 
with Arm 1. For example, once the 20 mg dose cohort of Arm 1 (MK-5890 monotherapy) 
and the 2 mg dose cohort of Arm 2 (MK-5890 + pembrolizumab) are open for enrollment, 
the first participant will be allocated to Arm 1, the second participant will be allocated to 
Arm 2, the third participant will be allocated to Arm 1, etc. An observation period of at least 
24 hours will occur between treatment initiation in the first 3 participants enrolled within 
each dose level. Each new dose cohort will open for enrollment without delay once the 
21-day DLT evaluation period of the previous dose cohort is completed and a dose escalation 
decision is made.
In Table 4, the columns indicate the number of participants evaluable for DLT at the current 
dose, and the rows indicate the number of participants with at least one DLT. The entries of 
the table are the dose-finding decisions: escalate to the next higher dose (E), stay at the 
current dose (S), de-escalate to the next lower dose (D), and de-escalate to a lower dose and 
never test this dose again (ie, unacceptably toxic dose; [DU]).
A minimum of 3 participants are required at each dose. Depending on the accrual rate and the 
occurrence of DLTs, 3, 4, 5, or 6 participants may be enrolled within 21 days at each new 
dose. For example, if 0 out of 3 participants at a given dose level develops a DLT, then the 
dose can escalate to the next level. If 1 out of 3 participants at a given dose level develops a 
DLT, then additional participants should be enrolled at that dose level following the rules 
below. If 2 participants out of 3 develop a DLT, the dose will be de-escalated to the next 
lower dose level. If 3 out of 3 participants develop a DLT, the dose should be de-escalated 
and the current dose will not be explored further.
When adding participants to a dose level in response to a “stay” decision, the number of 
additional participants to be enrolled is capped to minimize exposure to a dose that may be 
unacceptably toxic (denoted as DU in Table 4). To determine how many more participants
can be enrolled at the dose level, one can count steps in a diagonal direction (down and to the 
right) from the current cell to the first cell marked DU. For example, if 1 of 3 participants has
experienced a DLT at a given dose level, no more than an additional 3 participants should be 
enrolled at this dose level until additional DLT data are available. This is because this dose 
level would be considered unacceptably toxic if all 3 of the additional participants experience 
a DLT (ie, 4 out of 6 participants). The same principles will be applied whether 3, 4, 5, or 
6 participants are initially enrolled at a dose level.
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A dose-finding decision of D or DU at the lowest dose level will stop the study. An E 
decision at the highest dose level will result in staying at that level.
Dose finding will end after 14 participants have been enrolled at any of the tested doses 
(including intermediate doses). The dose of MK-5890 in the combination arm (Arm 2) may 
not be escalated to a dose that is higher than the MK-5890 dose in the MK-5890 
monotherapy arm (Arm 1), however, once dose escalation of MK-5890 in Arm 1 is stopped, 
the dose of MK-5890 in Arm 2 may be escalated up to that dose.
The pool-adjacent-violators-algorithm [Ji, Y. and Wang, S.-J. 2013] will be used to estimate 
the DLT rates across doses in each treatment arm. The dose with an estimated DLT rate 
closest to 30% will be treated as a preliminary RP2D, however, the totality of the data will be 
considered before deciding on the dose(s) to carry forward to the expansion phase, and the 
escalation schedule may be adjusted based on PD, PK, and safety data emerging throughout 
the study. The preliminary RP2D of MK-5890 in the combination arm (Arm 2) will not 
exceed, but may equal, the preliminary RP2D in the MK-5890 monotherapy arm (Arm 1).
Note that although 30% was the target toxicity rate used to generate the guidelines in
Table 4, the observed rates of participants with DLTs at the RP2Ds may be slightly above or 
below 30%.
Table 4
Dose-Finding Rules per the Modified Toxicity Probability Interval Design
Number of 
Participants with 
at Least 1 DLT
Number of Participants Evaluable for DLT at Current Dose
3
4
5
6
7
8
9
10
11
12
13
14
0
E
E
E
E
E
E
E
E
E
E
E
E
1
S
S
S
E
E
E
E
E
E
E
E
E
2
D
S
S
S
S
S
S
S
E
E
E
E
3
DU
DU
D
S
S
S
S
S
S
S
S
S
4
DU
DU
DU
D
D
S
S
S
S
S
S
5
DU
DU
DU
DU
DU
D
S
S
S
S
6
DU
DU
DU
DU
DU
DU
D
S
S
7
DU
DU
DU
DU
DU
DU
DU
D
8
DU
DU
DU
DU
DU
DU
DU
9
DU
DU
DU
DU
DU
DU
10
DU
DU
DU
DU
DU
11
DU
DU
DU
DU
12
DU
DU
DU
13
DU
DU
14
DU
E=Escalate to the next higher dose
S=Stay at the current dose
D=De-escalate to the next lower dose
DLT=dose-limiting toxicity
DU=The current dose is unacceptably toxic
Target toxicity rate = 30%
Flat non-informative prior Beta (1,1) is used as a prior and ε1=ε2=0.03 [Ji, Y., et al 2007] [Ji, Y. and Wang, 
S.-J. 2013]
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In addition to testing MK-5890 as monotherapy and combination treatment with 
pembrolizumab in participants with advanced solid tumors, the dose escalation and 
confirmation phase will also include a cohort of participants with nonsquamous NSCLC who 
will be treated with 30 mg MK-5890 in combination with 200 mg pembrolizumab, 
500 mg/m2 pemetrexed, and AUC 5 mg/mL/min carboplatin for up to 4 cycles followed by 
maintenance therapy with MK-5890, pembrolizumab, and pemetrexed (Arm 3). MK-5890 
will be given for up to a total of 6 months. Pembrolizumab and pemetrexed will be given for 
up to a total of 35 cycles with the possibility of continuing pemetrexed during the follow-up 
phase of the study at the discretion of the investigator per standard of care. All treatments 
will be given by IV infusion Q3W. For participants who continue pemetrexed after 35 cycles, 
pemetrexed will not be considered a new anticancer therapy. Enrollment in Arm 3 will begin 
with 6 participants. In the event of unacceptable toxicity during the chemotherapy 
combination, the doses of chemotherapy will be de-escalated according to the rules outlined 
in the mTPI design (Table 4). The chemotherapy doses that will be tested are outlined in
Table 3. Arm 3 may stop early if the number of DLTs exceeds an acceptable rate while at the 
lowest possible dose combination.
In Amendment 3, the dose expansion phase will also include a cohort of participants with 
locally recurrent inoperable TNBC not previously treated with chemotherapy and which 
cannot be treated with curative intent or with not previously treated metastatic TNBC whose 
tumor PD-L1 CPS is less than 10 who will be treated with 30 mg MK-5890 in combination 
with 400 mg pembrolizumab (Q6W), 100 mg/m2 nab-paclitaxel, administered by IV infusion 
administered on a 3-week on (Days 1, 8 and 15)/1-week off schedule every 28 days. MK-
5890 and pembrolizumab will be given for up to a total of 18 cycles. Enrollment in Arm 4
will begin with 10 participants. In the event of unacceptable toxicity during the 
chemotherapy combination, the doses of chemotherapy will be de-escalated according to the 
rules outlined in the mTPI design (Table 4). The chemotherapy doses that will be tested are 
outlined in Table 3. Arm 4 may stop early if the number of DLTs exceeds an acceptable rate 
while at the lowest possible dose combination.
Dose finding will end after 10 participants have been treated at a dose level of the 
chemotherapy combination as long as the decision based on Table 4 is to stay or escalate.
The doses of chemotherapy may not be de-escalated to doses lower than the lowest doses 
outlined in Table 3. If the mTPI design calls for a de-escalation beyond the lowest doses in 
Table 3, enrollment into Arm 3 will be closed.
5.5.7
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6. STUDY POPULATION
Male and female participants with advanced solid tumors who are at least 18 years of age on 
the day of signing consent will be enrolled in this study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
6.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Type of Participant and Disease Characteristics
1. a) Dose Escalation/Confirmation Phase (Arms 1 and 2): Have a histologically or 
cytologically confirmed advanced/metastatic solid tumor by pathology report and have 
received or been intolerant to all treatment known to confer clinical benefit.
b) Dose Escalation/Confirmation Phase (Arm 3): Have a histologically or cytologically 
confirmed diagnosis of stage IV (M1a or M1b per current AJCC criteria, edition 8) 
nonsquamous NSCLC.
Note: Mixed tumors will be categorized by the predominant cell type; if small cell 
elements are present, the participant is ineligible.
Participants may be untreated or could have received and progressed on 1 prior 
regimen.
Participants who have epidermal growth factor receptor (EGFR) or anaplastic 
lymphoma kinase (ALK) mutant tumors should have received an approved targeted 
therapy.
c) Dose Expansion Phase (Arm 2a): Have a diagnosis of TNBC. Participants must have 
received or been intolerant to not more than 2 lines of therapy for metastatic disease
known to confer clinical benefit. Prior therapy should have included anthracycline and/or 
taxane for early-stage or metastatic disease. Participants must have lactate dehydrogenase 
(LDH) ≤2 x ULN at screening. Enrollment will be capped at a maximum of 
7-10 participants who are PD-1/PD-L1 inhibitor treatment-refractory*.
d) Dose Expansion Phase (Arm 1a, 2b, and 2c): Have a diagnosis of endometrial cancer.
Participants must have received or been intolerant to no more than 2 prior lines of 
treatment known to confer clinical benefit. Prior therapy should have included
platinum-containing regimens for early-stage or metastatic disease. Enrollment will be 
capped at a maximum of 5-7 participants per treatment arm who are PD-1/PD-L1 
inhibitor treatment-refractory*.
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*Participants will be considered to have PD-1/PD-L1 inhibitor treatment-refractory 
disease if they meet all of the following criteria:
i.Have received at least 2 doses of anti-PD-1/PD-L1 mAb at a local regulatory 
agency-approved dose and schedule.
ii.Have progressive disease after anti-PD-1/PD-L1 mAb defined according to 
RECIST 1.1. The initial evidence of progressive disease is to be confirmed by a 
second assessment no less than 4 weeks from the date of the first documented 
progressive disease, in the absence of rapid clinical progression. Note: This
determination is made by the investigator. If progressive disease is confirmed, the 
initial date of progressive disease documentation will be considered the date of 
disease progression.
iii.Have documented disease progression within 12 weeks of the last dose of 
anti-PD-1/PD-L1 mAb. Participants who were re-treated with anti-PD-1/PD-L1 mAb 
and participants who were on maintenance with anti-PD-1/PD-L1 mAb will not be 
considered to have PD-1/PD-L1 inhibitor treatment-refractory disease if more than 
12 weeks elapse between disease progression and the last treatment date (with 
anti-PD1/PD-L1 therapy).
e) Dose Expansion Phase (Arm 4): Have TNBC with tumor PD-L1 CPS<10** that is
either locally recurrent, inoperable, not previously treated with chemotherapy, and which 
cannot be treated with curative intent or metastatic disease not previously treated with 
chemotherapy.
Note: Participants with a history of locally recurrent TNBC, which was previously 
treated with curative intent, may be eligible.
i. TNBC, as defined by the most recent ASCO/CAP guidelines. Note: Participants
initially diagnosed with hormone receptor–positive and/or HER2-positive breast 
cancer must have TNBC in a tumor biopsy obtained from a local recurrence or distant 
metastasis site.
ii. Have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months 
elapsed between the completion of treatment with curative intent (eg, date of primary 
breast tumor surgery or date of last adjuvant chemotherapy administration, whichever
occurred last) and first documented local or distant disease recurrence.
Note: Adjuvant radiation therapy is not considered treatment with curative intent for 
the purpose of calculating the ≥6-month interval requirement described above.
Note: First documentation of local or distant disease recurrence must be in the form 
of a dated biopsy, pathology, or imaging study report. A laboratory report indicating 
tumor marker elevation cannot be used as documentation of local or distant disease 
recurrence, unless accompanied by dated biopsy, pathology, or imaging study report.
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Note: Participants who received taxane agents in the (neo)adjuvant setting can be 
treated with same class of chemotherapy (taxane), if ≥12 months have elapsed 
between the completion of treatment with curative intent (eg, date of primary breast 
tumor surgery or date of last adjuvant chemotherapy administration, whichever 
occurred last) and first documented local or distant disease recurrence.
iii. Have been treated with (neo)adjuvant anthracycline, if they received systemic 
treatment in the (neo)adjuvant setting, unless anthracycline was contraindicated or not 
considered the best treatment option for the participant in the opinion of the treating 
physician.
Note: Participants presenting with de novo metastatic TNBC are eligible for the 
study, if anthracycline is contraindicated or not considered the best treatment option 
for the participant in the opinion of the treating physician.
**To calculate PD-L1 CPS, the PD-L1 IHC 22C3 pharmDx assay is required for 
PD-L1 testing. Tissue samples may be tested locally to determine eligibility. If local 
testing is used, each site investigator must ensure that PD-L1 testing is compliant with 
local regulations for guiding participant treatment decisions, notably that the PD-L1 
IHC 22C3 pharmDx test kit is used in accordance with instructions on the label.
Tissue samples will also be sent for central testing although participants can enter the 
study based on local PD-L1 IHC 22C3 pharmDx test results.
When PD-L1 IHC 22C3 pharmDx testing cannot be performed locally, central testing 
must be performed to determine eligibility.
2. Have measurable disease by RECIST 1.1. as assessed by the local site 
investigator/radiologist. Target lesions situated in a previously irradiated area are 
considered measurable if progression has been demonstrated in such lesions.
3. Have adequate organ function as defined in Table 5. Specimens must be collected within 
7 days before the first dose of study treatment.
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Table 5
Adequate Organ Function Laboratory Values
System / Parameter
Laboratory Value
HEMATOLOGICAL
Absolute neutrophil count (ANC)
>1500/µL
Platelet count
>100 000/µL
Hemoglobin1
≥9 g/dL or ≥5.6 mmol/L without transfusions within 
2 weeks of treatment initiation
RENAL
Creatinine 
OR
Measured or calculated creatinine 
clearance (CrCl)2
NOTE: Glomerular filtration rate (GFR) 
can be used in place of CrCl
Creatinine ≤1.5 × institutional upper limit of normal 
(ULN)
OR
CrCl (GFR) ≥50 mL/min for participants with 
creatinine levels >1.5 × institutional ULN
HEPATIC
Total bilirubin
OR
Direct bilirubin
Total bilirubin ≤1.5 × ULN
OR
Direct bilirubin ≤ULN for participants with total 
bilirubin levels >1.5 × ULN
Alanine aminotransferase (ALT) or 
serum glutamic-pyruvic transaminase
(SGPT)
AND
Aspartate aminotransferase (AST) or 
serum glutamic oxaloacetic transaminase
(SGOT)
≤2.5 × ULN
OR
≤5 × ULN for participants with liver metastases
COAGULATION
International Normalized Ratio (INR) or
Prothrombin time (PT)
≤1.5 × ULN unless the participant is receiving 
anticoagulant therapy
Activated partial thromboplastin time
(aPTT) or Partial thromboplastin time
(PTT)
≤1.5 × ULN unless the participant is receiving 
anticoagulant therapy
1 Criteria must be met without packed red blood cell (pRBC) transfusion within last 2 weeks. Participants 
can be on a stable dose of erythropoietin (≥ approximately 3 months).
2 Creatinine clearance (CrCl) should be calculated per institutional standard.
Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value 
requirements should be adapted according to local regulations and guidelines for the administration of 
specific chemotherapies.
Demographics
4. Be male or non-pregnant and non-breastfeeding female, ≥18 years of age on the day of 
signing informed consent.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Male participants:
6. A male participant must agree to use contraception as detailed in Appendix 3 of this 
protocol during the treatment period and for at least 120 days after the last dose of 
MK-5890 or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents
and refrain from donating sperm during this period.
Female participants:
7. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not 
breastfeeding, and at least one of the following conditions applies:
a.) She is not a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
b.) She is a WOCBP who agrees to follow the contraceptive guidance in Appendix 3
during the treatment period and for at least 120 days after the last dose of MK-5890 or 
pembrolizumab OR 180 days after the last dose of chemotherapeutic agents.
Informed Consent
8. The participant (or legally acceptable representative if applicable) provides documented 
informed consent/assent for the study. The participant may also provide consent/assent 
for Future Biomedical Research; however, he/she may participate in the study without 
participating in Future Biomedical Research.
Other Study-Specific Criteria
9. Submit an evaluable baseline tumor sample for analysis (either a newly obtained or 
archival tumor sample). Formalin-fixed, paraffin-embedded tissue blocks are preferred to 
slides. Newly obtained biopsies are preferred to archived tissue. Details pertaining to 
tumor tissue submission can be found in the Procedures Manual.
6.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Has a history of a second malignancy, unless potentially curative treatment has been 
completed with no evidence of malignancy for 2 years.
Note: The time requirement does not apply to the disease under study, participants who 
underwent successful definitive resection of basal cell carcinoma of the skin, squamous 
cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other 
in situ cancers.
2. Has clinically active central nervous system (CNS) metastases and/or carcinomatous 
meningitis. Participants with previously-treated brain or meningeal metastases may 
participate and be eligible for treatment provided they are stable and asymptomatic 
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(without evidence of progression by magnetic resonance imaging [MRI] scan of the brain 
separated by at least 4 weeks after treatment), have no evidence of new or enlarging brain 
metastases, are evaluated within 4 weeks before the start of study treatment, and are off 
immunosuppressive doses of systemic steroids for at least 2 weeks prior to enrollment.
3. Has had a severe hypersensitivity reaction to treatment with a mAb and/or other 
components of the study treatment.
4. Has an active infection requiring systemic treatment.
5. Has a history of interstitial lung disease.
6. Has a history of (noninfectious) pneumonitis that required steroids or current 
pneumonitis.
7. Has symptomatic ascites or pleural effusion. Participants who are clinically stable after 
treatment of these conditions (including therapeutic thoracocentesis or paracentesis) will 
not be excluded from participation in this study.
8. Has previously had a stem cell or bone marrow transplant.
9. Has previously had a solid organ transplant.
10. Has an active autoimmune disease that has required systemic treatment in the past 2 years 
(ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) 
except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as 
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or 
pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use 
of nonsystemic steroids is permitted.
11. Has known human immunodeficiency virus ([HIV]; HIV 1 or 2 antibodies) and/or active 
and acute Hepatitis B or C infections (eg, positive for HBsAg/HBV DNA or HCV RNA).
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the study, interfere with the participant’s participation 
for the full duration of the study, make administration of the study treatments hazardous,
or make it difficult to monitor adverse effects such that it is not in the best interest of the 
participant to participate, in the opinion of the treating investigator.
13. Has not fully recovered from any effects of major surgery without significant detectable 
infection. Surgeries that required general anesthesia must be completed at least 2 weeks 
before the start of study treatment. Surgeries that required regional/epidural anesthesia 
must be completed at least 72 hours before the first dose of study treatment and 
participants should be recovered.
14. Has known psychiatric or substance abuse disorders that would interfere with the 
participant’s ability to cooperate with the requirements of the study.
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15. Is pregnant or breastfeeding, or expecting to conceive or father children within the 
projected duration of the study.
16. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose 
of study treatment. If the urine test is positive or cannot be confirmed as negative, a 
serum pregnancy test will be required. In such cases, the participant must be excluded 
from participation if the serum pregnancy test result is positive. Note, in the event that 
72 hours have elapsed between the screening pregnancy test and the first dose of study 
treatment, another pregnancy test (urine or serum) must be performed and must be 
negative in order for the participant to start receiving study treatment.
Prior/Concomitant Therapy
17. Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks 
(2 weeks for palliative radiation) before the first dose of study treatment, or has not 
recovered to CTCAE Grade ≤1 or better from any AEs that were due to cancer 
therapeutics administered more than 4 weeks earlier (this includes participants with 
previous immunomodulatory therapy with residual immune-related AEs [irAEs]). 
Participants receiving ongoing replacement hormone therapy for endocrine irAEs will not 
be excluded from participation in this study.
18. Is expected to require any other form of antineoplastic therapy while participating in this 
study.
19. Has received prior therapy with an agent directed to another stimulatory T cell receptor 
(eg, CD27, OX-40, CD137).
20. Is on chronic systemic steroid therapy in excess of replacement doses (eg, exceeding 
10 mg/day of prednisone equivalent), or on any other form of immunosuppressive 
medication. Participants with reactive airway disease that require intermittent use of 
bronchodilators, inhaled steroids, or local steroid injections will not be excluded from this 
study.
21. Is a regular user (including “recreational use”) of any illicit drugs at the time of signing 
informed consent, or has a recent history (within the last year) of substance abuse 
(including alcohol), as determined by the treating investigator. Participants who use 
cannabis for medicinal purposes or to treat specific symptoms will not be excluded unless 
it is being abused in the opinion of the treating investigator.
22. Has received a live-virus vaccine within 28 days before the first dose of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, 
rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin 
(BCG), and typhoid vaccine. Seasonal flu vaccines that do not contain live viruses are 
permitted. Intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and 
are not permitted.
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Prior/Concurrent Clinical Study Experience
23. Is currently participating and receiving study therapy in a study of an investigational 
agent or has participated and received study therapy in a study of an investigational agent 
or has used an investigational device within 28 days before the first dose of study 
treatment.
Note: Participants who have entered the follow-up phase of an investigational study may 
participate as long as it has been 4 weeks since the last dose of the previous 
investigational agent.
Additional Exclusion Criteria for Participants Treated in Arm 3:
24. Has received radiation therapy to the lung that is >30 Gy within 6 months before the first 
dose of study treatment.
25. Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), 
other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting 
agents, such as piroxicam).
26. Is unable or unwilling to take folic acid or vitamin B12 supplementation.
Additional Exclusion Criteria for Participants Treated in Arm 4:
27. Has a known history of hypersensitivity or allergy to nab-paclitaxel or any of its 
components.
28. Has neuropathy ≥Grade 2. 
29. Has a history of class II-IV congestive heart failure or myocardial infarction within 6 
months of randomization. 
30. Has received previous treatment with immune checkpoint inhibitor(s) (eg, PD-1/PD-L1)
6.3
Lifestyle Restrictions
6.3.1
Meals and Dietary Restrictions
Participants should maintain a normal diet unless modifications are required to manage AEs 
such as diarrhea, nausea, or vomiting.
6.3.2
Caffeine, Alcohol, and Tobacco Restrictions
There are no restrictions on consumption of caffeine, alcohol, or tobacco.
6.3.3
Activity
There are no restrictions on activity.
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6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study.  A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any adverse events or serious adverse events 
(SAE) meeting reporting requirements as outlined in the data entry guidelines.
6.5
Participant Replacement Strategy
In order to adequately evaluate the safety of the doses of study treatment administered in this 
study, all participants enrolled in the dose escalation and confirmation phase and Arm 4 in 
the expansion phase must meet the criteria for DLT evaluability in DLT evaluation period
(see also Section 7.2.2). Participants are considered nonevaluable and will be replaced if:

They are allocated but not treated;

They discontinue from the study prior to completing all the safety evaluations in DLT 
evaluation period for reasons other than treatment-related AEs; and/or

They receive less than 75% of any of the study drugs in Cycle 1 (eg, because the 
infusion had to be discontinued due to an infusion reaction) and do not experience a 
DLT.
Participants who are not evaluable will be replaced unless accrual to the cohort has stopped. 
Nonevaluable participants will not be counted toward the total number of participants in the 
cohort for DLT evaluation.
7. TREATMENTS
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo,
or medical device(s) intended to be administered to a study participant according to the study 
protocol.
Clinical supplies [study treatment(s) provided by the Sponsor] will be packaged to support 
enrollment and replacement participants as required. When a replacement participant is 
required, the Sponsor or designee needs to be contacted prior to dosing the replacement 
supplies.  Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.
7.1
Treatments Administered
The study treatment(s) to be used in this study are outlined below in Table 6.
All study treatments will be administered on an out-patient basis.
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Table 6
Study Treatments
Study Treatment 
Name:
MK-5890 (Arms 1, 2, 3, 1a, 2a, 
2b, 2c, and 4)
Pembrolizumab 
(MK-3475; [Arms 2, 3, 
2a, 2b, 2c and 4])
Pemetrexed 
(Arm 3)
Carboplatin 
(Arm 3)
Nab-paclitaxel
(Arm 4)
Dose 
Formulation:
Solution for infusion
Solution for infusion
Lyophilized 
powder for 
injection
Solution for 
infusion
Lyophilized 
powder for 
injection
Unit Dose 
Strength(s):
50 mg/mL, 1.0 mL vial
25 mg/mL, 4.0 mL vial
500 mg
10 mg/mL, 60 mL 
vial
100 mg  
Dose Level(s):
Arms 1 and 2: Escalating doses 
based on pre-specified 
dose-limiting toxicity (DLT) 
criteria once every 3 weeks
Arms 3, 1a, 2a, 2b: 30 mg once 
every 3 weeks
Arms 2c and 4: 30 mg once 
every 6 weeks
Arms 2, 3, 2a, and 2b: 
200 mg once every 
3 weeks
Arms 2c and 4: 400 mg 
once every 6 weeks
500 mg/m2 once 
every 3 weeks
AUC 5 
mg/mL/min once 
every 3 weeks
100 mg/m2
Route of 
Administration:
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Sourcing:
Provided centrally by the 
Sponsor
Provided centrally by the 
Sponsor
Locally sourced
Locally sourced
Provided centrally 
by the Sponsor or 
locally sourced
IMP/NIMP:
IMP
IMP
IMP
IMP
IMP
AUC=area under the curve; IMP=investigational medicinal product; IV=intravenous; NIMP=non-investigational medicinal product
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All supplies indicated in Table 6 will be provided per the ‘Sourcing’ row depending upon 
local country operational requirements.  Every attempt should be made to source these 
supplies from a single lot/batch number. The study site is responsible for recording the lot 
number, manufacturer, and expiry date for any locally purchased product as per local 
guidelines unless otherwise instructed by the Sponsor.
Refer to Section 9.1.8 for details regarding administration of the study treatment.
7.2
Dose Modification (Escalation/Titration/Other)
7.2.1
Dose Administration/Escalation
7.2.1.1
CCI
CCI
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7.2.2
Definition of Dose-limiting Toxicity
All toxicities will be graded using the NCI CTCAE, version 4.0 or later based on investigator 
assessment.
The DLT evaluation period of observation will be during Cycle 1 (21 days for Arm 1 to Arm 
3).
In Arm 4, the DLT evaluation period will be during Cycle 1 of nab-paclitaxel (28 days).
The occurrence of any of the following toxicities during Cycle 1 will be considered a DLT, if 
assessed by the investigator to be possibly, probably, or definitely related to study treatment 
administration, excluding toxicities clearly not related to study treatment, such as disease 
progression, environmental factors, unrelated trauma, etc.
1. Any Grade 4 nonhematologic toxicity (not laboratory).
2. Any Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia:

Grade 4 thrombocytopenia of any duration;

Grade 3 thrombocytopenia associated with bleeding that requires a platelet 
transfusion.
3. Any nonhematologic AE Grade ≥3 in severity should be considered a DLT, with the 
following exceptions: Grade 3 fatigue lasting ≤3 days; Grade 3 diarrhea, nausea, or 
vomiting without use of anti-emetics or anti-diarrheals per standard of care; Grade 3 rash 
without use of corticosteroids or anti-inflammatory agents per standard of care.
4. Any Grade 3 or Grade 4 non-hematologic laboratory abnormality if:

Clinically significant medical intervention is required to treat the participant;

The abnormality leads to hospitalization;

The abnormality persists for >1 week; 

The abnormality results in a drug-induced liver injury (DILI) (see Sections 9.3.1 and 
9.3.7 for criteria).
CCI
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Exceptions: Clinically nonsignificant, treatable, or reversible laboratory abnormalities 
including liver function tests, uric acid, etc.
5. Grade 3 or Grade 4 febrile neutropenia:

Grade 3 is defined as absolute neutrophil count (ANC) <1000/mm3 with a single 
temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of 
≥38 degrees C (100.4 degrees F) for more than 1 hour.

Grade 4 is defined as ANC <1000/mm3 with a single temperature of >38.3 degrees C 
(101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for 
more than 1 hour, with life-threatening consequences and urgent intervention 
indicated.
6. Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity.
7. Any treatment-related toxicity that causes the participant to discontinue study treatment 
during Cycle 1.
8. Missing >25% of any study drug during the DLT evaluation period as a result of a 
drug-related AE(s).
9. Any Grade 5 toxicity.
If a participant experiences a DLT in DLT evaluation period study treatment may be 
discontinued following discussion between the Sponsor and the investigator. If the 
participant is deriving clinical benefit from the study treatment, the participant may be 
allowed to continue after discussion between the Sponsor and the investigator.
7.2.3
Cross-Over Treatment Phase (Optional)
Participants in the dose escalation and confirmation and dose expansion phases of the study 
with disease progression following treatment with MK-5890 in the monotherapy arms 
(Arm 1 and Arm 1a, respectively) may be eligible to participate in the cross-over treatment 
phase of this study. Participants who permanently discontinue MK-5890 monotherapy due to 
an AE, withdrawal of consent, or for any reason other than disease progression are not 
eligible for cross-over. Cross-over is optional, is at the discretion of the investigator, and 
requires the Sponsor’s approval.
Disease progression must be assessed by imaging study using RECIST 1.1. Imaging must be 
completed to establish a new baseline for the cross-over phase.
Additional eligibility criteria for cross-over include:
•
Participants must have adequate organ function as indicated by the laboratory values in 
Table 5;
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•
Participants must have no evidence of new or enlarging brain metastases; and
•
Participants must have an ECOG performance status of 0 or 1.
If cross-over is being considered, the participant must be re-consented and the risks and 
benefits of continuing study treatment after disease progression should be reviewed prior to 
performing any cross-over-related procedures.
Although intraparticipant dose escalation is not allowed, at cross-over, participants in the 
dose escalation and confirmation phase may be eligible to receive the highest dose of 
MK-5890 that has passed the DLT evaluation period in the MK-5890 + pembrolizumab 
combination treatment arm at the time of cross-over. If that dose is higher than the MK-5890 
dose the participant was receiving in the monotherapy arm, the increase in dose will be 
allowed only if the participant did not experience any drug-related AEs at the dose of 
MK-5890 the participant was receiving in the monotherapy arm. If that dose is lower than the 
MK-5890 dose the participant was receiving in the monotherapy arm, the MK-5890 dose the 
participant will receive in the combination treatment arm after cross-over will be de-escalated 
to the highest dose of MK-5890 that has passed an initial DLT evaluation period in the 
MK-5890 + pembrolizumab combination treatment arm. Participants who cross over to the 
MK-5890 + pembrolizumab combination treatment arm will not be counted toward the total 
number of participants in the cohort for DLT evaluation.
Participants in the dose expansion phase who cross over will receive 30 mg MK-5890.
The first dose of study treatment in the MK-5890 + pembrolizumab combination treatment 
arm should be administered no earlier than 21 days (3 weeks) and no later than 42 days 
(6 weeks) from the last dose of MK-5890 in the monotherapy arm unless otherwise discussed 
with the Sponsor.
Participants who cross over may receive up to 35 cycles of study treatment in the 
combination treatment arm after cross-over. Treatment duration after cross-over will not 
include the treatment duration in the monotherapy arm prior to cross-over.
The study procedures to be completed in the cross-over treatment phase and their timing are 
summarized in Section 2.8 (Schedule of Activities for the Cross-Over Treatment Phase). 
Safety and efficacy data from participants who cross over into the combination arm will be 
presented separately and will include all events starting from the date of the first dose of 
combination study treatment.
7.2.4
Timing of Dose Administration
Study treatment in Arms 1, 2, 3, 1a, 2a, and 2b will be administered by IV infusion Q3W. 
Study treatment in Arm 2c will be administered by IV infusion Q6W. MK-5890 will be 
administered over a period of approximately 90 minutes in all treatment arms. Based on 
preliminary safety information from the ongoing study, the Sponsor recommends that all 
participants treated with MK-5890 be prophylactically premedicated, 1.5 hours
(±30 minutes) before infusion of MK-5890; see Section 7.2.5.3 for details.
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In Arms 2, 3, 2a, 2b, and 2c, MK-5890 will be administered approximately 30 minutes after 
completion of the pembrolizumab infusion.
The order of infusions in Arm 3 will be as follows: pembrolizumab, MK-5890, pemetrexed, 
then carboplatin. Participants should receive premedication per the approved product labels 
for pemetrexed and carboplatin.
The order of infusions in Arm 4 will be as follows: pembrolizumab, MK-5890, then nab-
paclitaxel. Participants should receive premedication for nab-paclitaxel per the approved 
product labels.
Every effort should be made to begin the first dose of study treatment as close as possible to
the day of treatment allocation. All study treatments should be initiated after all pre-dose 
study procedures and assessments have been completed as detailed in Section 2.
In Arms 1 and 2, treatment in Cycle 2 may be administered up to 3 days after the scheduled 
Day 1, if necessary for administrative/logistical reasons. Beginning in Cycle 3, treatment 
may be administered up to 3 days before or 3 days after the scheduled Day 1 of each cycle. In 
Arm 3, treatment in Cycles 2-4 may be administered up to 3 days after the scheduled Day 1. 
Beginning in Cycle 5, treatment may be administered up to 3 days before or 3 days after the 
scheduled Day 1 of each cycle. In Arms 1a, 2a, 2b, and 2c and in participants who cross over 
to MK-5890 + pembrolizumab, treatment may be administered up to 3 days before or 3 days 
after the scheduled Day 1 of each cycle as of Cycle 2.
In addition, dose interruptions are permitted in the case of medical/surgical events or 
logistical reasons not related to study treatment (eg, elective surgery, unrelated medical 
events, participant vacations, and/or holidays). Participants should be placed back on study 
treatment within 3 weeks of the scheduled interruption, unless otherwise discussed with the 
Sponsor.
The reason for any variability in administration of study treatment outside of the 
protocol-specified window should be documented in the participant’s chart and recorded on 
the electronic Case Report Form (eCRF).
7.2.5
Immune-Related Events and Dose Modification (Withhold, Treat, 
Discontinue)
7.2.5.1
Dose Modification and Toxicity Management for Adverse Events Associated 
With MK-5890 and/or Pembrolizumab
Adverse events (both nonserious and serious) associated with MK-5890 and pembrolizumab 
exposure may represent an immunologic etiology. These AEs may occur anywhere from 
shortly after the first dose to several months after the last dose of treatment.
The NCI CTCAE, version 4.0 or later must be used to grade the severity of AEs. The 
investigator may attribute each toxicity event to MK-5890 alone, to pembrolizumab alone, or 
to the combination, and modify the dose as appropriate. If a dose modification for toxicity 
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occurs with MK-5890, the dose may not be re-escalated to the dose that preceded the dose 
modification. Dose modifications are always based on the previous cycle.
Reduction or holding of 1 agent and not the other agent is appropriate if, in the opinion of the 
investigator, the toxicity is clearly related to 1 of the study treatments. For example, in the 
MK-5890 + pembrolizumab combination arms (Arms 2, 3, 2a, 2b, and 2c), if MK-5890 is 
held due to an AE attributed to that treatment, then pembrolizumab may continue to be 
administered. The investigator must appropriately document the attribution of the AE. If, in 
the opinion of the investigator, the toxicity is related to the combination of the 2 agents, then 
both treatments should be held according to recommended dose modifications.
Participants may have up to 2 dose modifications of MK-5890 throughout the course of the 
study, as described in Table 7. If further toxicity occurs or the criteria for resuming treatment 
are not met, the participant must be discontinued from study treatment. If a participant 
experiences several toxicities and there are conflicting recommendations, the most 
conservative dose adjustment recommendation should be followed (ie, dose reduction 
appropriate to the most severe toxicity).
Dose modification and treatment discontinuation guidelines for AEs related to MK-5890 are 
outlined in Table 7. The Sponsor may consider exceptions to the dose modification 
guidelines, after consultation.
Pembrolizumab treatment interruption/discontinuation and toxicity management guidelines
are described in Section 7.2.5.2 and treatment guidelines associated with infusion-related 
reactions are described in Section 7.2.5.3.
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Table 7
MK-5890 Dose Modification and Treatment Discontinuation Guidelines for 
Drug-Related Adverse Events
Toxicity
Hold 
Treatment
Criteria for 
Restarting 
Treatment
Dose/Schedule 
for Restarting 
Treatment
Criteria for 
Discontinuation 
after Consultation 
with Sponsor
Hematological toxicities:
Any Grade 1 hematological 
toxicity
No
N/A
N/A
N/A
Any Grade 2 hematological 
toxicity, or Grade 3 toxicity 
that persists for ≤5 days
Per medical 
assessment 
of the 
investigator
If treatment 
held, may be 
restarted when 
AE resolves to 
baseline or 
Grade 1
Per medical
assessment of the 
investigator; may 
decrease dose by 
1 dose level
If AE persists for 
12 weeks without 
resolution following 
reduction in dose
Any Grade 3 hematologic 
toxicity that persists for 
>5 days, or Grade 4 
hematological toxicity; or
Febrile neutropenia; or
Grade 3 thrombocytopenia 
of any duration if associated 
with bleeding
Yes
Treatment may 
be restarted 
when AE 
resolves to 
baseline or 
Grade 1
Decrease dose by 
1 dose level
If AE persists for 
12 weeks without 
resolution following 
reduction in dose
Permanent study 
treatment 
discontinuation 
should be considered 
for any severe or life-
threatening event
Nonhematological toxicities:
Any Grade 1 
nonhematological toxicity; 
or
Grade 2 alopecia; or
Grade 2 fatigue
No
N/A
N/A
N/A
Any Grade 2 
nonhematological toxicity 
except Grade 2 alopecia and 
Grade 2 fatigue
Per medical 
assessment 
of the 
investigator
If treatment 
held, may be 
restarted when 
AE resolves to 
baseline or 
Grade 1
Per medical 
assessment of the 
investigator; may 
decrease dose by 1 
dose level
If AE persists for 
12 weeks without 
resolution following 
reduction in dose
Any Grade 3 or Grade 4 
nonhematological toxicity 
(not including laboratory
abnormalities, unless 
clinically significant 
medical intervention is 
required, the abnormality 
leads to hospitalization, or 
the abnormality persists for 
>1 week)
Yes
Treatment may 
be restarted 
when AE 
resolves to 
baseline or 
Grade 1
Decrease dose by 
1 dose level
If AE persists for 
12 weeks without 
resolution following 
reduction in dose
Permanent study 
treatment 
discontinuation 
should be considered 
for any severe or life-
threatening event
AE=adverse event; N/A=not applicable
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In case toxicity does not resolve to Grade 0-1 within 12 weeks after the last dose of study 
treatment, MK-5890 should be discontinued after consultation with the Sponsor.
With investigator and Sponsor agreement, participants with a laboratory abnormality still at 
Grade 2 after 12 weeks may continue treatment in the study only if asymptomatic and 
controlled.
After any Grade 4, drug-related AE, participants should not restart study treatment without
consultation with the Sponsor; the toxicity must have resolved to baseline or Grade 0-1 prior 
to restarting.
7.2.5.2
Dose Modification and Toxicity Management for Immune-Related AEs 
Associated With Pembrolizumab
AEs associated with pembrolizumab exposure may represent an immune-related response. 
These irAEs may occur shortly after the first dose or several months after the last dose of 
pembrolizumab treatment and may affect more than one body system simultaneously. 
Therefore, early recognition and initiation of treatment is critical to reduce complications. 
Based on existing clinical study data, most irAEs were reversible and could be managed with 
interruptions of pembrolizumab, administration of corticosteroids, and/or other supportive 
care. For suspected irAEs, ensure adequate evaluation to confirm etiology or exclude other 
causes. Additional procedures or tests such as bronchoscopy, endoscopy, and/or skin biopsy 
may be included as part of the evaluation. Based on the severity of irAEs, withhold or 
permanently discontinue pembrolizumab and administer corticosteroids. 
Dose Modification and Toxicity Management Guidelines for irAEs associated with 
pembrolizumab monotherapy, coformulations, or IO combinations are provided in Table 8.
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Table 8
Dose Modification and Toxicity Management Guidelines for Immune-related Adverse Events Associated With 
Pembrolizumab Monotherapy, Coformulations or IO Combinations
General instructions:
1.
Severe and life-threatening irAEs should be treated with IV corticosteroids followed by oral steroids. Other immunosuppressive treatment should begin 
if the irAEs are not controlled by corticosteroids.
2.
Pembrolizumab monotherapy, coformulations or IO combinations must be permanently discontinued if the irAE does not resolve or the corticosteroid 
dose is not ≤10 mg/day within 12 weeks of the last treatment. 
3.
The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue at least 4 weeks.
4.
If pembrolizumab monotherapy, coformulations or IO combinations have been withheld, treatment may resume after the irAE decreased to ≤Grade 1 
after corticosteroid taper.
irAEs
Toxicity Grade 
(CTCAEv4.0)
Action With 
Pembrolizumab 
Monotherapy, 
Coformulations or 
IO Combinations
Corticosteroid and/or Other 
Therapies
Monitoring and Follow-up
Pneumonitis 
Grade 2
Withhold 
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or equivalent) 
followed by taper
Monitor participants for signs and symptoms of 
pneumonitis
Evaluate participants with suspected pneumonitis 
with radiographic imaging and initiate corticosteroid 
treatment
Add prophylactic antibiotics for opportunistic 
infections
Recurrent Grade 2 
or Grade 3 or 4 
Permanently 
discontinue
Diarrhea / Colitis 
Grade 2 or 3
Withhold
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or equivalent) 
followed by taper
Monitor participants for signs and symptoms of 
enterocolitis (ie, diarrhea, abdominal pain, blood or 
mucus in stool with or without fever) and of bowel 
perforation (ie, peritoneal signs and ileus)
Participants with ≥Grade 2 diarrhea suspecting colitis 
should consider GI consultation and performing 
endoscopy to rule out colitis
Participants with diarrhea/colitis should be advised to 
drink liberal quantities of clear fluids. If sufficient 
oral fluid intake is not feasible, fluid and electrolytes 
should be substituted via IV infusion.
Recurrent Grade 3 
or Grade 4
Permanently 
discontinue
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irAEs
Toxicity Grade 
(CTCAEv4.0)
Action With 
Pembrolizumab 
Monotherapy, 
Coformulations or 
IO Combinations
Corticosteroid and/or Other 
Therapies
Monitoring and Follow-up
AST / ALT 
Elevation or 
Increased 
Bilirubin
Grade 2
Withhold
Administer corticosteroids 
(initial dose of 0.5-1 mg/kg 
prednisone or equivalent) 
followed by taper
Monitor with liver function tests (consider weekly or 
more frequently until liver enzyme value returned to 
baseline or is stable)
Grade 3 or 4 
Permanently 
discontinue
Administer corticosteroids 
(initial dose of 1-2 mg/kg 
prednisone or equivalent) 
followed by taper
T1DM or 
Hyperglycemia
New onset T1DM 
or 
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of β-cell 
failure
Withhold a
Initiate insulin replacement 
therapy for participants with 
T1DM
Administer anti-
hyperglycemic in participants 
with hyperglycemia
Monitor participants for hyperglycemia or other signs 
and symptoms of diabetes
Hypophysitis
Grade 2
Withhold
Administer corticosteroids 
and initiate hormonal 
replacements as clinically 
indicated
Monitor for signs and symptoms of hypophysitis 
(including hypopituitarism and adrenal insufficiency)
Grade 3 or 4
Withhold or 
permanently 
discontinue a
Hyperthyroidism 
Grade 2
Continue
Treat with non-selective 
beta-blockers (eg, 
propranolol) or thionamides 
as appropriate
Monitor for signs and symptoms of thyroid disorders
Grade 3 or 4
Withhold or 
Permanently 
discontinue a
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irAEs
Toxicity Grade 
(CTCAEv4.0)
Action With 
Pembrolizumab 
Monotherapy, 
Coformulations or 
IO Combinations
Corticosteroid and/or Other 
Therapies
Monitoring and Follow-up
Hypothyroidism
Grade 2-4
Continue
Initiate thyroid replacement 
hormones (eg, levothyroxine 
or liothyronine) per standard 
of care
Monitor for signs and symptoms of thyroid disorders
Nephritis and 
renal dysfunction
Grade 2
Withhold
Administer corticosteroids 
(prednisone 1-2 mg/kg or 
equivalent) followed by taper
Monitor changes of renal function
Grade 3 or 4
Permanently 
discontinue
Myocarditis
Grade 1 
Withhold
Based on severity of AE 
administer corticosteroids
Ensure adequate evaluation to confirm etiology 
and/or exclude other causes
Grade 2, 3 or 4
Permanently 
discontinue
All Other irAEs
Persistent Grade 2
Withhold
Based on severity of AE 
administer corticosteroids
Ensure adequate evaluation to confirm etiology or 
exclude other causes
Grade 3
Withhold or 
discontinue b
Recurrent Grade 3 
or Grade 4 
Permanently 
discontinue
AE(s)=adverse event(s); ALT= alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common Terminology Criteria for Adverse Events; DRESS=Drug Rash 
with Eosinophilia and Systemic Symptom; GI=gastrointestinal; IO=immuno-oncology; ir=immune related; IV=intravenous; SJS=Stevens-Johnson Syndrome; T1DM=type 1 
diabetes mellitus; TEN=Toxic Epidermal Necrolysis; ULN=upper limit of normal.
Note: Non-irAE will be managed as appropriate, following clinical practice recommendations.
a
The decision to withhold or permanently discontinue pembrolizumab monotherapy, coformulations or IO combinations is at the discretion of the investigator or treating 
physician. If control achieved or ≤ Grade 2, pembrolizumab monotherapy, coformulations or IO combinations may be resumed.
b
Events that require discontinuation include, but are not limited to: Guillain-Barre Syndrome, encephalitis, myelitis, DRESS, SJS, TEN and other clinically important irAEs (eg, 
vasculitis and sclerosing cholangitis).
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7.2.5.3
Toxicity Management of Infusion Reactions Related to Pembrolizumab and 
MK-5890
Pembrolizumab and MK-5890 may cause severe or life-threatening infusion reactions 
including severe hypersensitivity or anaphylaxis. Signs and symptoms usually develop 
during or shortly after drug infusion and generally resolve completely within 24 hours of 
completion of the infusion.
Based on preliminary safety information from the ongoing study, the Sponsor recommends 
that all participants treated with MK-5890 be prophylactically premedicated, 1.5 hours
(±30 minutes) before infusion of MK-5890 with the following:

Diphenhydramine 50 mg orally (or equivalent dose of antihistamine); and

Acetaminophen 500-1000 mg orally (or equivalent dose of analgesic).
Corticosteroids may be added after consultation with the Sponsor.
Depending on the timing of premedication, these may be administered before 
pembrolizumab, if necessary.
Toxicity management guidelines for pembrolizumab-associated infusion reactions are 
provided in Table 9.
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Table 9
Infusion Reaction Treatment Guidelines
NCI CTCAE Grade
Treatment
Premedication at 
Subsequent Dosing
Grade 1
Mild reaction; infusion 
interruption not 
indicated; intervention 
not indicated
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator
None
Grade 2
Requires therapy or 
infusion interruption but 
responds promptly to 
symptomatic treatment 
(eg, antihistamines, 
nonsteroidal 
anti-inflammatory drugs 
[NSAIDs], narcotics, 
IV fluids); prophylactic 
medications indicated 
for ≤24 hours
Stop infusion
Additional appropriate medical therapy may 
include, but is not limited to:
IV fluids
Antihistamines
NSAIDs
Acetaminophen
Narcotics
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator
If symptoms resolve within 1 hour of stopping drug 
infusion, the infusion may be restarted at 50% of 
the original infusion rate (eg, from 100 mL/hr to 
50 mL/hr). Otherwise dosing will be held until 
symptoms resolve and the participant should be 
premedicated for the next scheduled dose
Participants who develop Grade 2 toxicity 
despite adequate premedication should be 
permanently discontinued from further study 
treatment
Participant may be 
premedicated 1.5 hours 
(±30 minutes) prior to 
infusion of
pembrolizumab with:
Diphenhydramine 
50 mg PO (or 
equivalent dose of 
antihistamine)
Acetaminophen 
500-1000 mg PO (or 
equivalent dose of 
analgesic)
Grade 3 or 4
Grade 3:
Prolonged (ie, not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following 
initial improvement; 
hospitalization indicated 
for other clinical 
sequelae (eg, renal 
impairment, pulmonary 
infiltrates)
Grade 4:
Life-threatening; pressor 
or ventilatory support 
indicated
Stop infusion
Additional appropriate medical therapy may 
include, but is not limited to:
Epinephrine**
IV fluids
Antihistamines
NSAIDs
Acetaminophen
Narcotics
Oxygen
Pressors
Corticosteroids
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator
Hospitalization may be indicated
**In cases of anaphylaxis, epinephrine should be 
used immediately
Participant is permanently discontinued from 
further study treatment
No subsequent dosing
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the 
period of study treatment administration.
For further information, please refer to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 at 
http://ctep.cancer.gov
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7.2.5.4
Dose Modification for Chemotherapy
Participants should receive premedication per the approved product labels for pemetrexed,
carboplatin and nab-paclitaxel.
Recommended dose modifications for key chemotherapy toxicities are outlined in Table 10
and Table 11. These serve only as a guide and do not replace investigator judgment and 
applicable local label recommendations, if more stringent. Please refer to Table 3 for 
definitions of the dose levels.
Dose modifications for individual study treatment(s) must be based on the maximum toxicity 
experienced during the previous treatment period with this(these) drug(s) and must be 
performed in a stepwise manner, as described in Table 10 and Table 11. Toxicity (except for 
alopecia) needs to resolve to ≤Grade 1 or baseline prior to resuming treatment with the same 
drug(s). For participants requiring a study treatment dose modification, the next treatment 
period with this(these) drug(s) may be delayed, if the scheduled off-drug periods are not 
adequate to allow for recovery to ≤Grade 1 or the baseline status of the participant. If a dose 
reduction for toxicity occurs with chemotherapy, the dose(s) may not be re-escalated. 
Participants may have a maximum of 2 dose modifications per chemotherapy (if applicable) 
for toxicities throughout the course of the study. If a participant experiences several toxicities 
and there are conflicting recommendations, the most conservative dose adjustment 
recommended should be followed (dose reduction appropriate to the most severe toxicity). 
If the toxicity may be attributed to both an immunologic etiology (pembrolizumab-related) 
and chemotherapy, pembrolizumab should be interrupted or discontinued and chemotherapy 
should be reduced (if applicable), interrupted, or discontinued, according to local guidelines 
and practices. Participants may have chemotherapy discontinued and continue on 
pembrolizumab and MK-5890. Similarly, participants may discontinue pembrolizumab 
and/or MK-5890 and continue on chemotherapy, if appropriate. Chemotherapy 
administration may be interrupted due to AEs for a maximum of 4 weeks.
Use of colony-stimulating factors (CSFs) for primary prophylaxis is permitted at the 
investigator’s discretion. Refer to the American Society of Clinical Oncology guidelines for 
use of CSFs [Smith, T. J., et al 2006].
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Table 10
Recommended Dose Modifications for Chemotherapy-Related Hematological 
Toxicities
Platelets
ANC
Carboplatin
Pemetrexed
Dose level from Table 3
≥50,000/mcL
AND
≥500/mcL
DL 0
DL 0
≥50,000/mcL
AND
<500/mcL
DL -1
DL -1
<50,000/mcL without 
bleeding
AND
ANY
DL -1
DL -1
<50,000/mcL with 
Grade ≥2 bleeding
AND
ANY
DL -2
DL -2
ANY
AND
<1,000/mcL + fever 
≥38.5°C (101°F)
DL -1
DL -1
DL=dose level
Table 11
Recommended Dose Modifications for Chemotherapy-Related 
Non-Hematological Toxicities
Event
CTCAE Grade
Carboplatin
Pemetrexed
Dose level from Table 3
Nausea or vomiting
Grade 3or 4
DL 0
DL 0
Diarrhea
Grade 3or 4
DL 0
DL -1
Mucositis
Grade 3or 4
DL 0
DL -2
Neurotoxicity
Grade 2
DL 0
DL 0
Grade 3or 4
DL -1
DL -1
Transaminase elevation
Grade 3
DL -1
DL -1
Grade 4
Discontinue treatment
Discontinue treatment
Other non-hematological
toxicities
Grade 3or 4
DL -1
DL -1
CTCAE=Common Terminology Criteria for Adverse Events; DL=dose level
Suggested dose modifications for nab-paclitaxel should follow local guidelines and practices.
Creatinine clearance (CrCl): CrCl will be based on the original weight-based 
Cockcroft-Gault Method or institutional standard. CrCl must be ≥45 mL/min prior to the 
administration of chemotherapy. Carboplatin and/or pemetrexed may be delayed for up to 
42 days to allow the participant time to recover from the toxicity. If a participant’s CrCl 
value has not returned to ≥45 mL/min within 42 days after the previous dose, carboplatin
and/or pemetrexed must be discontinued.
7.2.5.5
Management Guidelines for Overlapping Toxicities
For overlapping toxicities where it is unclear if the event is related to one or a combination of
drugs, it is recommended to hold all applicable drugs, and initiate management per MK-5890 
Dose Modification and Treatment Discontinuation Guidelines for Drug-Related Adverse 
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Events (Table 7) for MK-5890 treatment and per Dose Interruption/Discontinuation and 
Toxicity Management Guidelines for Immune-Related Adverse Events Associated with 
Pembrolizumab (Table 8) for pembrolizumab treatment. Table 10 and Table 11 or standard 
of care should be followed for management of toxicities deemed related to chemotherapy.
7.3
Method of Treatment Assignment
Treatment allocation will occur centrally using an IVRS/IWRS.
Participants in the dose escalation and confirmation phase of the study will be allocated by 
non-random assignment to 1 of 2 treatment arms: escalating doses of MK-5890 Q3W as 
monotherapy (Arm 1) or escalating doses of MK-5890 Q3W in combination with 200 mg 
pembrolizumab Q3W (Arm 2).
Enrollment into the MK-5890 + pembrolizumab combination treatment arm (Arm 2) will 
begin once all participants at the second dose level in the MK-5890 monotherapy arm 
(Arm 1) complete the DLT evaluation period and a dose escalation decision has been made. 
This ensures that the starting dose of MK-5890 in the combination arm will be at least 
2 levels below the dose being tested in the MK-5890 monotherapy arm. When both treatment 
arms are open for enrollment, IVRS/IWRS will alternate participant assignment between 
Arms 1 and 2 starting with Arm 1. For example, once the 20 mg dose cohort of Arm 1 
(MK-5890 monotherapy) and the 2 mg dose cohort of Arm 2 (MK-5890 + pembrolizumab) 
are open for enrollment, the first participant will be allocated to Arm 1, the second 
participant will be allocated to Arm 2, the third participant will be allocated to Arm 1, etc. An 
observation period of at least 24 hours will occur between treatment initiation in the first 
3 participants enrolled within each dose level. Each new dose cohort will open for enrollment 
without delay once the 21-day DLT evaluation period of the previous dose cohort is 
completed and a dose escalation decision is made.
Participants with nonsquamous NSCLC enrolled as part of Amendment 02 will be allocated 
to combination treatment with 30 mg MK-5890, 200 mg pembrolizumab, 500 mg/m2
pemetrexed, and AUC 5 mg/mL/min carboplatin, all given Q3W (Arm 3).
Participants in the dose expansion phase of the study with TNBC will be allocated to 30 mg 
MK-5890 Q3W in combination with 200 mg pembrolizumab Q3W (Arm 2a). Participants in 
the dose expansion phase of the study with endometrial will be allocated by random 
assignment at a 1:1:1 ratio to 30 mg MK-5890 Q3W as monotherapy (Arm 1a), 30 mg 
MK-5890 Q3W in combination with 200 mg pembrolizumab Q3W (Arm 2b), or 30 mg 
MK-5890 Q6W in combination with 400 mg pembrolizumab Q6W (Arm 2c).
In addition, participants with locally recurrent inoperable TNBC cancer not previously 
treated with chemotherapy and which cannot be treated with curative intent or with  
previously not treated metastatic TNBC whose tumor PD-L1 CPS is less than 10 (Arm 4) 
will be allocated to 30 mg MK-5890 in combination with 400 mg pembrolizumab and 100 
mg/m2 nab-paclitaxel; MK-5890 and pembrolizumab given Q6W for 18 cycles and nab-
paclitaxel will be administered on a 3-week on (Days 1, 8 and 15)/1-week off schedule every 
28 days.
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7.3.1
Stratification
No stratification based on age, sex or other characteristics will be used in this study.
7.4
Blinding
This is an open-label study; therefore, the Sponsor, investigator and participant will know the 
treatment administered.
7.5
Preparation/Handling/Storage/Accountability
7.5.1
Dose Preparation
Details on preparation and administration of MK-5890 and pembrolizumab are provided in 
the Pharmacy Manual. Pemetrexed and carboplatin should be prepared and administered per
their approved product labels.
The rationale for selection of doses to be used in this study is provided in 
Section 5.5 - Justification for Dose.  There are no specific calculations or evaluations 
required to be performed in order to administer the proper dose to each participant.
7.5.2
Handling, Storage and Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported 
and resolved before use of the study treatment.
Only participants enrolled in the study may receive study treatment and only authorized site 
staff may supply or administer study treatment. All study treatments must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized site 
staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records).
For all study sites, the local country Sponsor personnel or designee will provide appropriate 
documentation that must be completed for drug accountability and return, or local discard 
and destruction if appropriate.  Where local discard and destruction is appropriate, the 
investigator is responsible for ensuring that a local discard/destruction procedure is 
documented.
The study site is responsible for recording the lot number, manufacturer, and expiry date for 
any locally purchased product as per local guidelines unless otherwise instructed by the 
Sponsor.
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The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of study 
treatments in accordance with the protocol and any applicable laws and regulations.
7.6
Treatment Compliance
Administration of study treatment(s) will be witnessed by the investigator and/or study staff. 
The total volume of study treatment infused will be compared with the total volume prepared 
to determine compliance with each dose administered.
Interruptions from the protocol specified treatment plan for ≥12 weeks require consultation 
between the investigator and the Sponsor and written documentation of the collaborative 
decision on participant management.
7.7
Concomitant Therapy
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the study. If there is a clinical indication for any medication or vaccination 
specifically prohibited, discontinuation from study treatment may be required. The 
investigator should discuss any questions regarding this with the Sponsor. The final decision 
on any supportive therapy or vaccination rests with the investigator and/or the participant’s 
primary physician. The decision to continue the participant on study treatment, however,
requires the mutual agreement of the investigator, the Sponsor, and the participant.
7.7.1
Acceptable Concomitant Medication
All treatments that the investigator considers necessary for a participant’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care except for those that are prohibited as described in Section 7.7.2. All 
concomitant medication will be recorded on the case report form (CRF) including all 
prescription, over-the-counter (OTC), herbal supplements, and IV medications and fluids. If 
changes occur during the study period, documentation of drug dosage, frequency, route, and 
date may also be included on the CRF.
All concomitant medications received within 28 days before the first dose of study treatment 
and up to 30 days after the last dose of study treatment should be recorded. Concomitant 
medications administered after the 30-day post-study treatment period related to SAEs and 
ECIs as defined in Section 9.3 should be recorded.
7.7.2
Prohibited Concomitant Medications
Participants are prohibited from receiving the following concomitant therapies and
vaccinations during the screening and treatment periods of the study:

Immunotherapy not specified in this protocol

Antineoplastic systemic chemotherapy or biological therapy not specified in this 
protocol
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
Investigational agents not specified in this protocol

Radiation therapy (radiotherapy for symptom management is allowed)

Live vaccines within 28 days before the first dose of study treatment and while 
participating in the study. Examples of live vaccines include, but are not limited to, 
the following: measles, mumps, rubella, chickenpox, yellow fever, rabies, BCG, and 
typhoid vaccines. Seasonal influenza vaccines for injection are generally killed virus 
vaccines and are allowed. Intranasal influenza vaccines (eg, FluMist®) are live 
attenuated vaccines, and are not allowed.

Glucocorticoids other than to modulate symptoms from an immune-mediated AE
and/or as pre/post-medication to prevent AEs associated with chemotherapy. Chronic 
systemic replacement doses of steroids and non-systemic steroids including inhaled 
steroids, topical steroids, intra-nasal steroids, intra-articular, and ophthalmic steroids
are allowed.

Phenytoin during treatment with carboplatin

Participants taking NSAIDs or salicylates will not take the NSAID or salicylate (other 
than an aspirin dose ≤1.3 g per day) for 2 days before, the day of, and 2 days after 
receiving pemetrexed. Participants taking NSAIDs or salicylates with a long half-life 
(eg, naproxen, piroxicam, diflunisal, or nabumetone) will not take the NSAID or 
salicylates for 5 days before, the day of, and 2 days after pemetrexed.
There are no prohibited therapies after the Post-Treatment Safety Follow-Up visit.
7.7.3
Rescue Medications and Supportive Care
Participants should receive appropriate supportive care measures as deemed necessary by the 
treating investigator. Suggested supportive care measures for the management of AEs with 
potential immunologic etiology are outlined in Section 7.2.5.2, Table 8. Toxicity 
management guidelines for infusion reactions related to pembrolizumab and MK-5890 are
outlined in Section 7.2.5.3, Table 9. Where appropriate, these guidelines include the use of 
oral or IV treatment with corticosteroids, as well as additional anti-inflammatory agents if 
symptoms do not improve with administration of corticosteroids. Note that several courses of 
steroid tapering may be necessary as symptoms may worsen when the steroid dose is 
decreased. For each disorder, attempts should be made to rule out other causes such as 
metastatic disease or bacterial or viral infection, which might require additional supportive 
care. The treatment guidelines are intended to be applied when the investigator determines 
the events to be related to study treatment.
Note: If after evaluation of the event, it is determined not to be related to MK-5890 and/or 
pembrolizumab, the investigator does not need to follow the treatment guidance.
It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, or 
skin photography as part of the evaluation of the event.
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7.7.3.1
Antiemetic Use
For participants receiving chemotherapy, antiemetic therapy should follow MASCC; 
Section 12.9) or appropriate local guidelines and should, for the first 4 cycles, include a 
5-HT3 receptor antagonist, dexamethasone (or equivalent), and aprepitant (or equivalent 
NK-1 receptor antagonist) as per the guideline followed.
7.7.3.2
Colony-Stimulating Factors
For participants receiving chemotherapy, the ASCO guidelines for use of CSFs, or local 
equivalent, should be used for patient management [Smith, T. J., et al 2006]. Use of CSFs for 
primary prophylaxis is permitted at the investigator’s discretion.
7.7.3.3
Pemetrexed Premedication
All participants must receive the appropriate supplementation of vitamin B12, folic acid, and 
corticosteroid prophylaxis as listed below or per the local label:

Folic acid, 350 μg to 1000 μg orally: At least 5 doses of folic acid must be taken 
during the 7 days preceding the first dose of pemetrexed, through the full course of 
therapy, and for 21 days after the last dose of pemetrexed.

Vitamin B12, 1000 μg by IM injection: Vitamin B12 must be given in the week 
preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent 
vitamin B12 injections may be given on the same day as pemetrexed.

Dexamethasone prophylaxis, 4 mg orally twice per day (or equivalent):
Dexamethasone may be taken the day before, day of, and day after pemetrexed 
administration. Higher or additional doses are permitted for antiemetic prophylaxis 
during Cycles 1 through 4 but are not to exceed doses in MASCC guidelines 
(Section 12.9) or appropriate local guidelines.
7.7.3.4
Nab-paclitaxel Premedication
Premedication for nab-paclitaxel is determined according to local label.
7.8
Treatment After the End of the Study
There is no study-specified treatment following the end of the study.
7.9
Clinical Supplies Disclosure
This study is open-label; therefore, the participant, the study site personnel, the Sponsor 
and/or designee are not blinded. Study treatment (name, strength or potency) is included in 
the label text; random code/disclosure envelopes or lists are not provided.
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8. DISCONTINUATION/WITHDRAWAL CRITERIA
8.1
Discontinuation of Study Treatment
Discontinuation of study treatment does not represent withdrawal from the study.
As certain data on clinical events beyond study treatment discontinuation may be important 
to the study, they must be collected through the participant’s last scheduled follow-up, even 
if the participant has discontinued study treatment.  Therefore, all participants who 
discontinue study treatment prior to completion of the protocol-specified treatment period
will still continue to participate in the study as specified in Section 2 - Schedule of Activities 
(SoA) and Section 9.10.3 – Discontinued Participants Continuing to be Monitored in the 
Study.
Participants may discontinue study treatment at any time for any reason or be dropped from 
the study treatment at the discretion of the investigator should any untoward effect occur.  In 
addition, a participant may be discontinued from study treatment by the investigator or the 
Sponsor if study treatment is inappropriate, the study plan is violated, or for administrative 
and/or other safety reasons.  Specific details regarding procedures to be performed at study 
treatment discontinuation are provided in Section 9.1.9 – Discontinuation and Withdrawal.
A participant must be discontinued from study treatment but continue to be monitored in the 
study for any of the following reasons:
○
The participant or participant’s legally acceptable representative requests to discontinue 
study treatment.
o
The participant experiences confirmed radiographic disease progression as outlined in 
Section 9.2 (except if the Sponsor approves treatment continuation).
o
The participant experiences unacceptable adverse experiences as described in Section 9.3.
o
The participant experiences intercurrent illness that prevents further administration of 
study treatment.
o
The participant has a medical condition or personal circumstance, which in the opinion of 
the investigator and/or the Sponsor, places the participant at unnecessary risk if study 
treatment administration is continued.
o
The participant experiences recurrent Grade 2 pneumonitis.
o
The participant experiences progression or recurrence of any malignancy, or any 
occurrence of another malignancy that requires active treatment.
o
The participant has a confirmed positive serum pregnancy test.
o
The participant does not comply with study treatment or procedure requirements.
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o
The investigator decides to withdraw the participant.
o
The participant completes study treatment (ie, Arms 1 and 1a: 35 cycles of MK-5890; 
Arm 2: 35 cycles of MK-5890/pembrolizumab; Arm 3: 6 months of MK-5890/35 cycles 
of pembrolizumab/35 cycles of pemetrexed [with the possibility of continuing during the 
follow-up phase of the study]/4 cycles of carboplatin; Arms 2a and 2b: 6 months of 
MK-5890/35 cycles of pembrolizumab; Arm 2c: 6 months of MK-5890/18 cycles of 
pembrolizumab; and Arm 4: 30 mg MK-5890 (Q6W) for up to 18 cycles in combination 
with 400 mg pembrolizumab (Q6W) for up to 18 cycles and 100 mg/m2 nab-paclitaxel
administered on a 3-week on (Days 1, 8 and 15)/1-week off schedule every 28 days).
Note: The number of treatment cycles is calculated starting with the first dose.
Participants in the dose escalation and confirmation and dose expansion phases of the study 
who discontinue MK-5890 in the monotherapy arm due to disease progression may, at the 
investigator’s discretion and after consultation with the Sponsor, cross-over to
MK-5890 + pembrolizumab combination treatment as described in Section 7.2.3. The 
number of treatment cycles for cross-over participants will be calculated starting with the 
first dose of MK-5890 + pembrolizumab combination treatment.
If a participant experiences a DLT in DLT evaluation period, study treatment may be 
discontinued following discussion between the Sponsor and the investigator. If the 
participant is deriving clinical benefit from the study treatment, the participant may be 
allowed to continue after discussion between the Sponsor and the investigator.
If a participant initiates another anticancer therapy other than the assigned study treatment(s), 
the study treatment(s) should be discontinued and the participant will move into the survival 
follow-up phase. Note: For participants in Arm 3 who continue pemetrexed after 35 cycles, 
pemetrexed will not be considered a new anticancer therapy.
8.2
Withdrawal from the Study
A participant must be withdrawn from the study if the participant or participant’s legally 
acceptable representative withdraws consent from the study.
If a participant withdraws from the study, they will no longer receive study treatment or be 
followed at scheduled protocol visits.
Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from Future Biomedical Research are 
outlined in Section 9.1.9 – Discontinuation and Withdrawal. The procedures to be performed 
should a participant repeatedly fail to return for scheduled visits and/or if the study site is 
unable to contact the participant are outlined in Section 8.3.
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8.3
Lost to Follow Up
If a participant fails to return to the clinic for a required study visit and/or if the site is unable 
to contact the participant, the following procedures are to be performed:
●
The site must attempt to contact the participant and reschedule the missed visit.  If the
participant is contacted, the participant should be counseled on the importance of
maintaining the protocol-specified visit schedule.
●
The investigator or designee must make every effort to regain contact with the
participant at each missed visit (eg, phone calls and/or a certified letter to the
participant’s last known mailing address or locally equivalent methods). These
contact attempts should be documented in the participant’s medical record.
●
Note:  A participant is not considered lost to follow-up until the last scheduled visit
for the individual participant.  The missing data for the participant will be managed
via the pre-specified statistical data handling and analysis guidelines.
9. STUDY ASSESSMENTS AND PROCEDURES
●
Study procedures and their timing are summarized in the SoA.
●
Adherence to the study design requirements, including those specified in the SoA, is
essential and required for study conduct.
●
The Investigator is responsible for assuring that procedures are conducted by
appropriately qualified or trained staff.  Delegation of study site personnel
responsibilities will be documented in the Investigator Trial File Binder (or
equivalent).
●
All screening evaluations must be completed and reviewed to confirm that potential
participants meet all eligibility criteria. The investigator will maintain a screening log
to record details of all participants screened and to confirm eligibility or record
reasons for screening failure, as applicable.
●
Procedures conducted as part of the participant’s routine clinical management (eg,
blood count) and obtained before signing of ICF may be utilized for screening or
baseline purposes provided the procedure met the protocol-specified criteria and were
performed within the time frame defined in the SoA.
●
Additional evaluations/testing may be deemed necessary by the investigator and or
the Sponsor for reasons related to participant safety. In some cases, such
evaluation/testing may be potentially sensitive in nature (eg, HIV, Hepatitis C, etc.),
and thus local regulations may require that additional informed consent be obtained
from the participant.  In these cases, such evaluations/testing will be performed in
accordance with those regulations.
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The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, is outlined in the Procedures 
Manual.
9.1
Administrative and General Procedures
9.1.1
Informed Consent
The investigator or qualified designee must obtain documented consent from each potential 
participant or each participant’s legally acceptable representative prior to participating in a 
clinical study or Future Biomedical Research. If there are changes to the participant’s status 
during the study (eg, health or age of majority requirements), the investigator or qualified 
designee must ensure the appropriate consent is in place. 
9.1.1.1
General Informed Consent
Consent must be documented by the participant’s dated signature or by the participant’s 
legally acceptable representative’s dated signature on a consent form along with the dated 
signature of the person conducting the consent discussion. 
A copy of the signed and dated consent form should be given to the participant before 
participation in the study.
The initial ICF, any subsequent revised written ICF and any written information provided to 
the participant must receive the IRB/IEC’s approval/favorable opinion in advance of use.  
The participant or his/her legally acceptable representative should be informed in a timely 
manner if new information becomes available that may be relevant to the participant’s 
willingness to continue participation in the study.  The communication of this information 
will be provided and documented via a revised consent form or addendum to the original 
consent form that captures the participant’s dated signature or by the participant’s legally 
acceptable representative’s dated signature.
Specifics about a study and the study population will be added to the consent form template 
at the protocol level.  
The informed consent will adhere to IRB/IEC requirements, applicable laws and regulations 
and Sponsor requirements.
9.1.1.2
Consent and Collection of Specimens for Future Biomedical Research
The investigator or medically qualified designee will explain the FBR consent to the 
participant, answer all of his/her questions, and obtain documented informed consent before 
performing any procedure related to FBR.  A copy of the informed consent will be given to 
the participant before performing any procedure related to FBR.
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9.1.2
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee 
to ensure that the participant qualifies for the study.
9.1.3
Participant Identification Card
All participants will be given a Participant Identification Card identifying them as 
participants in a research study. The card will contain study site contact information 
(including direct telephone numbers) to be utilized in the event of an emergency. The 
investigator or qualified designee will provide the participant with a Participant Identification 
Card immediately after the participant provides documented informed consent. At the time of 
treatment allocation/randomization, site personnel will add the treatment/randomization 
number to the Participant Identification Card.
The participant identification card also contains contact information for the emergency 
unblinding call center so that a health care provider can obtain information about study 
treatment in emergency situations where the investigator is not available.
9.1.4
Medical History
A medical history will be obtained by the investigator or qualified designee.
Medical history will include all active conditions, and any condition diagnosed within the 
prior 10 years that are considered to be clinically significant by the investigator. Details 
regarding the disease for which the participant has enrolled in the study will be recorded 
separately and not listed as medical history.
9.1.5
Prior and Concomitant Medications Review
9.1.5.1
Prior Medications
The investigator or qualified designee will review prior medication use, including any 
protocol-specified washout requirement, and record prior medication taken by the participant 
within 28 days before starting the study. Treatment for the disease for which the participant 
has enrolled in the study will be recorded separately and not listed as a prior medication.
9.1.5.2
Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the participant 
during the study through the Post-Treatment Safety Follow-Up visit.
All medications related to reportable SAEs and ECIs should be recorded as defined in 
Section 9.3.
All new anticancer therapy initiated after the study start must be recorded on the eCRF.
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9.1.6
Assignment of Screening Number
All consented participants will be given a unique screening number that will be used to 
identify the participant for all procedures that occur prior to treatment allocation.  Each 
participant will be assigned only one screening number.  Screening numbers must not be re-
used for different participants.
Any participant who is screened multiple times will retain the original screening number 
assigned at the initial screening visit.
Specific details on the screening visit requirements (screening/rescreening) are provided in 
Section 9.10.1.
9.1.7
Assignment of Treatment/Randomization Number
All eligible participants in the study will be allocated to a study treatment and will receive a 
treatment/randomization number. The treatment/randomization number identifies the 
participant for all procedures occurring after treatment allocation/randomization. Once a 
treatment/randomization number is assigned to a participant, it can never be re-assigned to 
another participant.
A single participant cannot be assigned more than 1 treatment/randomization number.
9.1.8
Treatment Administration
Administration of study treatment will be witnessed by the investigator and/or study staff.
The total volume of study treatment infused will be compared to the total volume prepared to 
determine compliance with each dose administered.
9.1.8.1
Timing of Dose Administration
All study treatments will be administered by IV infusion on an out-patient basis. In Arms 1
and 1a (MK-5890 monotherapy), Arms 2, 2a, and 2b (MK-5890 and pembrolizumab), and 
Arm 3 (MK-5890, pembrolizumab, pemetrexed, and carboplatin), study treatment will be 
administered Q3W, ie, on Day 1 of every 21-day cycle. In Arm 2c, MK-5890 and 
pembrolizumab will be administered Q6W, ie, on Day 1 of every 42-day cycle.
MK-5890 will be administered over a period of approximately 90 minutes in all treatment 
arms. Based on preliminary safety information from the ongoing study, the Sponsor
recommends that all participants treated with MK-5890 be prophylactically premedicated,
1.5 hours (±30 minutes) before infusion of MK-5890; see Section 7.2.5.3 for details.
In Arms 2, 3, 2a, 2b, and 2c, pembrolizumab will be administered first, with administration 
of MK-5890 occurring approximately 30 minutes after completion of the pembrolizumab 
infusion.
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The order of infusions in Arm 3 will be as follows: pembrolizumab, MK-5890, pemetrexed, 
then carboplatin. Participants should receive premedication per the approved product labels 
for pemetrexed and carboplatin.
The order of infusions in Arm 4 will be as follows: pembrolizumab, MK-5890, then nab-
paclitaxel. Participants should receive premedication per the approved product labels for nab-
paclitaxel.  
9.1.9
Discontinuation and Withdrawal
Participants who discontinue study treatment prior to completion of the treatment period
should be encouraged to continue to be followed for all remaining study visits.
When a participant withdraws from participation in the study, all applicable activities 
scheduled for the final study visit should be performed (at the time of withdrawal).  Any 
adverse events which are present at the time of withdrawal should be followed in accordance 
with the safety requirements outlined in Section 9.3.
9.1.9.1
Withdrawal From Future Biomedical Research
Participants may withdraw their consent for Future Biomedical Research.  Participants may 
withdraw consent at any time by contacting the principal investigator for the study.  If 
medical records for the study are still available, the investigator will contact the Sponsor 
using the designated mailbox (clinical.specimen.management@MSD.com).  Subsequently, 
the participant's consent for Future Biomedical Research will be withdrawn.  A letter will be 
sent from the Sponsor to the investigator confirming the withdrawal. It is the responsibility of 
the investigator to inform the participant of completion of withdrawal.  Any analyses in 
progress at the time of request for withdrawal or already performed prior to the request being 
received by the Sponsor will continue to be used as part of the overall research study data 
and results.  No new analyses would be generated after the request is received.
In the event that the medical records for the study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the study records) or the 
specimens have been completely anonymized, there will no longer be a link between the 
participant’s personal information and their specimens.  In this situation, the request for 
specimen withdrawal cannot be processed.
9.1.10
Participant Blinding/Unblinding
This is an open label study; there is no blinding for this study.
9.1.11
Calibration of Critical Equipment
The investigator or qualified designee has the responsibility to ensure that any critical device 
or instrument used for a clinical evaluation/test during a clinical study that provides 
important information about inclusion/exclusion criteria and/or safety or efficacy parameters 
shall be suitably calibrated and maintained to ensure that the data obtained is reliable and/or 
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reproducible.  Documentation of equipment calibration must be retained as source 
documentation at the study site.
Additional guidance regarding critical equipment (if applicable) is provided in the 
Procedures Manual, Pharmacy Manual, and Site Imaging Manual.
9.2
Efficacy Assessments
9.2.1
Tumor Imaging and Assessment of Disease
Tumor imaging should be acquired by computed tomography ([CT], strongly preferred). 
Magnetic resonance imaging should be used when CT is contraindicated or for imaging in 
the brain. The same imaging technique regarding modality, ideally the same scanner, and use 
of contrast should be used in a participant throughout the study to optimize the visualization
and reproducibility of the assessment of existing and new tumor burden and improve the 
accuracy of the assessment of response or progression based on imaging. The schedule of 
disease assessment should not be adjusted for delays, if any, in cycle starts.
Response will be assessed by the investigator; however, scans used for tumor measurements 
may be requested for potential central review.
9.2.1.1
Initial Tumor Imaging
Initial tumor imaging at screening must be performed within 28 days before the first dose of 
study treatment. Scans performed as part of routine clinical management are acceptable for 
use as screening tumor imaging if they are of diagnostic quality and performed within the 
timeframe defined in the SoA. The site study team must review screening images to confirm 
the participant has measurable disease per RECIST 1.1.
Participants with previously-treated brain metastases may participate provided they have 
stable brain metastases, ie, without evidence of progression by imaging (confirmed by MRI if 
MRI was used at prior imaging, or confirmed by CT imaging if CT was used at prior 
imaging) for at least 4 weeks before the first dose of study treatment. Any neurologic 
symptoms must have returned to baseline and participants must have no evidence of new or 
enlarging brain metastases, and have not used steroids for brain metastases for at least 
28 days before starting the study as per local site assessment. This exception does not include 
carcinomatous meningitis, as participants with carcinomatous meningitis are excluded 
regardless of clinical stability.
9.2.1.2
Tumor Imaging During the Study
The first on-study imaging assessment should be performed 9 weeks (±7 days) after the first 
dose of study treatment. Subsequent tumor imaging should be performed every 9 weeks 
(±7 days), or more frequently if clinically indicated. Imaging timing should follow calendar 
days and should not be adjusted for delays in cycle starts. Imaging should continue to be 
performed until disease progression, initiating a new anticancer therapy, participant 
withdrawal of consent, pregnancy, becoming lost to follow-up, or death, whichever occurs 
first.
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Per RECIST 1.1, objective response should be confirmed by a repeat imaging assessment. 
Tumor imaging to confirm partial response (PR) or complete response (CR) should be 
performed at least 4 weeks after the first indication of a response is observed. Participants 
will then return to regular scheduled imaging every 9 weeks, starting with the next scheduled 
imaging time point. Participants who receive additional imaging for confirmation do not need 
to undergo the next scheduled tumor imaging if it is less than 4 weeks later; tumor imaging 
may resume at the subsequent scheduled imaging time point.
Per iRECIST [Seymour, L., et al 2017], disease progression should be confirmed by the site 
4 to 8 weeks after the first radiologic evidence of progressive disease in clinically stable 
participants. Participants who have unconfirmed disease progression may continue on study 
treatment at the discretion of the investigator until progression is confirmed by the site 
provided they have met the conditions detailed in Section 9.2.1.5. Participants who receive 
confirmatory imaging do not need to undergo the next scheduled tumor imaging if it is less 
than 4 weeks later; tumor imaging may resume at the subsequent scheduled imaging time 
point, if clinically stable. Participants who have confirmed disease progression by iRECIST, 
as assessed by the site, will discontinue study treatment. Exceptions are detailed in 
Section 9.2.1.5.
9.2.1.3
End of Treatment and Follow-Up Tumor Imaging
In participants who discontinue study treatment, tumor imaging should be performed at the 
time of treatment discontinuation (±4 weeks). If previous imaging was obtained within 
4 weeks before the date of discontinuation, then imaging at treatment discontinuation is not 
mandatory. For participants who discontinue study treatment due to documented disease 
progression and the investigator elects not to implement iRECIST, this is the final required 
tumor imaging.
For participants who discontinue study treatment without documented disease progression, 
every effort should be made to continue monitoring their disease status by tumor imaging 
using the same imaging schedule used while on treatment (every 9 weeks) to monitor disease 
status until disease progression, initiating a new anticancer therapy, participant withdrawal of 
consent, pregnancy, becoming lost to follow-up, or death, whichever occurs first.
9.2.1.4
RECIST 1.1 Assessment of Disease
RECIST 1.1 will be used as the primary measure for assessment of tumor response, date of 
disease progression, and as a basis for all protocol guidelines related to disease status (eg, 
discontinuation of study treatment). Although RECIST 1.1 references a maximum of 5 target 
lesions in total and 2 per organ, the Sponsor allows a maximum of 10 target lesions in total 
and 5 per organ, if clinically relevant to enable a broader sampling of tumor burden.
9.2.1.5
iRECIST 1.1 Assessment of Disease
iRECIST is based on RECIST 1.1, but adapted to account for the unique tumor response seen 
with immunotherapeutic drugs. iRECIST will be used by the investigator to assess tumor 
response and progression, and make treatment decisions. When clinically stable, participants 
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should not be discontinued until progression is confirmed by the investigator, working with 
local radiology, according to the rules outlined in Appendix 7. This allowance to continue 
treatment despite initial radiologic progressive disease takes into account the observation that 
some participants can have a transient tumor flare in the first few months after the start of 
immunotherapy, and then experience subsequent disease response. This data will be captured 
in the clinical database.
Until radiographic progression based on RECIST 1.1, there is no distinct iRECIST 
assessment.
Clinical stability is defined as the following:
•
Absence of symptoms and signs indicating clinically significant progression of disease
•
No decline in ECOG performance status
•
No requirements for intensified management, including increased analgesia, radiation, or 
other palliative care
Any participant deemed clinically unstable should be discontinued from study treatment at 
site-assessed first radiologic evidence of progressive disease, and is not required to have 
repeat tumor imaging for confirmation of disease progression by iRECIST.
If the investigator decides to continue treatment, the participant may continue to receive 
study treatment and the tumor assessment should be repeated 4 to 8 weeks later to confirm 
disease progression by iRECIST, per investigator assessment. 
If repeat imaging does not confirm disease progression per iRECIST, as assessed by the 
investigator, and the participant continues to be clinically stable, study treatment may 
continue and follow the regular imaging schedule. If disease progression is confirmed, 
participants will be discontinued from study treatment.
If a participant has confirmed radiographic progression (iRECIST confirmed progressive 
disease [iCPD]) as defined in Appendix 7, study treatment should be discontinued; however, 
if the participant is achieving a clinically meaningful benefit, an exception to continue study 
treatment may be considered following consultation with the Sponsor. In this case, if study 
treatment is continued, tumor imaging should continue to be performed following the 
intervals outlined in Section 2.
A description of the adaptations and iRECIST process is provided in Appendix 7, with 
additional details in the iRECIST publication. A summary of imaging and treatment 
requirements after first radiologic evidence of progression is provided in [Table 12]  and 
illustrated as a flowchart in [Figure 3].
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Table 12
Imaging and Treatment After First Radiologic Evidence of Progressive Disease
Clinically Stable
Clinically Unstable
Imaging
Treatment
Imaging
Treatment
First radiologic evidence of 
PD by RECIST 1.1 per 
investigator assessment
Repeat imaging at 4 to 
8 weeks to confirm PD
May continue study treatment at 
the investigator’s discretion 
while awaiting confirmatory 
tumor imaging by iRECIST
Repeat imaging at 4 to 
8 weeks to confirm PD at 
the investigator’s 
discretion ONLY
Discontinue study treatment
Repeat tumor imaging 
confirms PD (iCPD) by 
iRECIST per investigator 
assessment
No additional imaging 
required
Discontinue study treatment 
(exception is possible upon 
consultation with Sponsor)
No additional imaging 
required
Not applicable
Repeat tumor imaging 
shows iUPD by iRECIST 
per investigator assessment
Repeat imaging at 4 to 
8 weeks to confirm PD. 
May occur at next 
regularly scheduled 
imaging visit
Continue study treatment at the 
investigator’s discretion
Repeat imaging at 4 to 
8 weeks to confirm PD at 
the investigator’s 
discretion ONLY
Discontinue study treatment
Repeat tumor imaging 
shows iSD, iPR, or iCR by 
iRECIST per investigator 
assessment.
Continue regularly 
scheduled imaging 
assessments
Continue study treatment at the 
investigator’s discretion
Continue regularly 
scheduled imaging 
assessments
May restart study treatment if 
condition has improved and/or 
clinically stable at the 
investigator’s discretion. Next 
tumor image should occur 
according to the regular imaging 
schedule
iCPD=iRECIST confirmed progressive disease; iCR=iRECIST complete response; iPR=iRECIST partial response; iRECIST=modified Response Evaluation Criteria in Solid 
Tumors 1.1 for immune-based therapeutics; iSD=iRECIST stable disease; iUPD=iRECIST unconfirmed progressive disease; PD=progressive disease; RECIST 1.1=Response 
Evaluation Criteria in Solid Tumors 1.1
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Figure 3
Imaging and Treatment for Clinically Stable Participants After First Radiologic 
Evidence of Progressive Disease
iRECIST=modified Response Evaluation Criteria in Solid Tumors 1.1 for immune-based therapeutics; PD=progressive 
disease; RECIST 1.1=Response Evaluation Criteria in Solid Tumors 1.1
9.2.2
Eastern Cooperative Oncology Group (ECOG) Performance Scale
The investigator or qualified designee will assess ECOG status as specified in the SoA.
9.3
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Reportable 
Safety Events
The definitions of an adverse event (AE) and serious adverse event (SAE), as well as the 
method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting AE, SAE, and other reportable safety event reports can be 
found in Appendix 4.
Progression of the cancer under study is not considered an adverse event unless it results in 
hospitalization or death as described in Section 9.3.5 – Disease-Related Events and/or 
Disease-Related Outcomes Not Qualifying as AEs or SAEs, and Appendix 4.
AEs, SAEs, and other reportable safety events will be reported by the participant (or, when 
appropriate, by a caregiver, surrogate, or the participant's legally authorized representative). 
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The investigator, who is a qualified physician, and any designees are responsible for 
detecting, assessing, documenting, and reporting events that meet the definition of an AE or 
SAE as well as other reportable safety events. Investigators remain responsible for following 
up AEs, SAEs, and other reportable safety events for outcome according to Section 9.3.3.
Adverse events will not be collected for participants during the pre-screening period (for 
determination of archival tissue status) as long as that participant has not undergone any 
protocol-specified procedure or intervention.  If the participant requires a blood draw, fresh 
tumor biopsy etc., the participant is first required to provide consent to the main study and 
AEs will be captured according to guidelines for standard AE reporting.
9.3.1
Time Period and Frequency for Collecting AE, SAE, and Other Reportable 
Safety Event Information
All AEs, SAEs, and other reportable safety events that occur after the participant provides 
documented informed consent but before treatment allocation/randomization must be 
reported by the investigator if the participant is receiving placebo run-in or other run-in 
treatment, if the event causes the participant to be excluded from the study, or is the result of 
a protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, or a procedure. 
●
All AEs from the time of treatment allocation/randomization through 30 days following 
cessation of study treatment must be reported by the investigator. 
●
All AEs meeting serious criteria, from the time of treatment allocation/randomization 
through 90 days following cessation of study treatment, or 30 days following cessation of 
study treatment if the participant initiates new anticancer therapy, whichever is earlier 
must be reported by the investigator. 
●
All pregnancies and exposure during breastfeeding, from the time of treatment 
allocation/randomization through 120 days following cessation of MK-5890 or 
pembrolizumab OR 180 days after the last dose of chemotherapeutic agents, or 30 days 
following cessation of study treatment if the participant initiates new anticancer therapy 
must be reported by the investigator. 
●
Additionally, any SAE brought to the attention of an investigator at any time outside of 
the time period specified above must be reported immediately to the Sponsor if the event 
is considered to be drug-related.
Investigators are not obligated to actively seek AE or SAE or other reportable safety events 
in former study participants. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study treatment or study participation, the 
investigator must promptly notify the Sponsor.
All initial and follow-up AEs, SAEs, and other reportable safety events will be recorded and 
reported to the Sponsor or designee within the timeframes as indicated in Table 13.
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Table 13
Reporting Time Periods and Timeframes for Adverse Events and Other 
Reportable Safety Events
Type of Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-Specified 
Follow-up Period
Reporting Time 
Period:
After the Protocol 
Specified Follow-up 
Period
Timeframe to 
Report Event 
and Follow-
up 
Information 
to 
SPONSOR:
Non-Serious Adverse 
Event (NSAE) 
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is 
receiving placebo 
run-in or other run-in 
treatment
Report all
Not required
Per data entry 
guidelines
Serious Adverse Event 
(SAE) including 
Cancer and Overdose
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is 
receiving placebo 
run-in or other run-in 
treatment
Report all
Report if:
- drug/vaccine related.
(Follow ongoing to 
outcome)
Within 24 
hours of 
learning of 
event
Pregnancy/
Lactation Exposure
Report if:
- due to intervention
- causes exclusion
Report all
Previously reported –
Follow to completion/
termination; report 
outcome
Within 24 
hours of 
learning of 
event
Event of Clinical 
Interest (require 
regulatory reporting)
Report if:
- due to intervention
- causes exclusion
Report
- Potential DILI
- Require regulatory 
reporting
Not required
Within 24 
hours of 
learning of 
event
Event of Clinical 
Interest (Do not 
require regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- non-DILI ECIs and 
those not requiring 
regulatory reporting
Not required
Within 5 
calendar days 
of learning of 
event
9.3.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events
Care will be taken not to introduce bias when detecting AE and/or SAE and other reportable 
safety events. Open-ended and non-leading verbal questioning of the participant is the 
preferred method to inquire about AE occurrence.
9.3.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs, SAEs, and other reportable safety events 
including pregnancy and exposure during breastfeeding, ECI, Cancer and Overdose will be 
followed until resolution, stabilization, until the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 8.3). In addition, the investigator will 
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make every attempt to follow all non-serious AEs that occur in treated participants for 
outcome.  Further information on follow-up procedures is given in Appendix 4.
9.3.4
Regulatory Reporting Requirements for SAE
●
Prompt notification (within 24 hours) by the investigator to the Sponsor of SAE is 
essential so that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are met. 
●
The Sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study treatment under clinical 
investigation. All AEs will be reported to regulatory authorities, IRB/IECs, and 
investigators in accordance with all applicable global laws and regulations, ie, per 
ICH Topic E6 (R1) Guidelines for Good Clinical Practice.
●
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy 
and forwarded to investigators as necessary.
●
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAE) from the Sponsor will file 
it along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate 
according to local requirements.
9.3.5
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs
Progression of the cancer under study is not considered a reportable event unless it results in 
hospitalization or death.
9.3.6
Pregnancy and Exposure During Breastfeeding
Although pregnancy and infant exposure during breastfeeding are not considered adverse 
events, any pregnancy or infant exposure during breastfeeding in a participant (spontaneously 
reported to the investigator or their designee) that occurs during the study are reportable to 
the Sponsor.
All reported pregnancies must be followed to the completion/termination of the pregnancy. 
Pregnancy outcomes of spontaneous abortion, missed abortion, benign hydatidiform mole, 
blighted ovum, fetal death, intrauterine death, miscarriage and stillbirth must be reported as 
serious events (Important Medical Events). If the pregnancy continues to term, the outcome 
(health of infant) must also be reported.
9.3.7
Events of Clinical Interest (ECIs)
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported to the Sponsor.
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Events of clinical interest for this study include: 
1. an overdose of Sponsor's product, as defined in Section 9.4 – Treatment of Overdose, that 
is not associated with clinical symptoms or abnormal laboratory results.
2. an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of 
normal and an elevated total bilirubin lab value that is greater than or equal to 2X the 
upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less 
than 2X the upper limit of normal, as determined by way of protocol-specified laboratory 
testing or unscheduled laboratory testing.*
*Note:  These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require 
an additional evaluation for an underlying etiology. The study site guidance for 
assessment and follow up of these criteria can be found in the Investigator Trial File 
Binder (or equivalent).
9.4
Treatment of Overdose
For purposes of this study, an overdose will be defined as any dose exceeding the prescribed 
dose for MK-5890 by ≥20% of the indicated dose. An overdose of pembrolizumab will be 
defined as any dose of 1000 mg or greater. No specific information is available on the 
treatment of overdose of MK-5890 or pembrolizumab. In the event of overdose, 
MK-5890/pembrolizumab should be discontinued and the participant should be observed 
closely for signs of toxicity.  Appropriate supportive treatment should be provided if 
clinically indicated.
9.5
Safety
Details regarding specific safety procedures/assessments to be performed in this study are 
provided below.
Planned time points for all safety assessments are provided in the SoA.
9.5.1
Physical Examinations
The investigator or qualified designee will perform a full physical examination at screening, 
Cycle 1, and at the End of Treatment visit. Directed physical examinations may be done at 
the other time points unless a full examination is deemed necessary.
Clinically significant abnormal findings at screening should be recorded as medical history. 
After the first dose of study treatment, new clinically significant abnormal findings should be 
recorded as AEs.
9.5.2
Vital Signs
The investigator or qualified designee will take vital sign measurements, which include 
temperature, pulse, respiratory rate, and blood pressure.
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9.5.3
Electrocardiograms
A standard 12-lead ECG will be performed using local standard procedures. Additional 
ECGs at time points not specified in the SoA may be performed as clinically necessary.
Clinically significant abnormal findings before the first dose of study treatment should be 
recorded as medical history. After the first dose of study treatment, new clinically significant 
abnormal findings should be recorded as AEs.
9.5.4
Clinical Safety Laboratory Assessments
Refer to Appendix 5 for the list of clinical laboratory tests to be performed and to the SoA for 
the timing and frequency. 
●
The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
CRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected 
for the participant's condition.
●
All protocol-required laboratory assessments, as defined in Appendix 5, must be 
conducted in accordance with the Laboratory Manual and the SoA.
●
If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in study participant management or 
are considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the appropriate CRF (eg, SLAB).
●
For any laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 30 days after the last dose of study 
treatment, every attempt should be made to perform repeat assessments until the 
values return to normal or baseline or if a new baseline is established as determined 
by the investigator. 
9.5.4.1
Laboratory Safety Evaluations (Hematology, Chemistry, and Urinalysis)
Laboratory tests for hematology, chemistry, and urinalysis are specified in Appendix 5. At 
screening, these tests should be performed within 7 days before the first dose of study 
treatment. Pre-dose hematology and chemistry testing can be conducted up to 72 hours 
before the first dose of study treatment unless otherwise noted in Section 2. If screening tests 
are performed within 72 hours before the first dose of study treatment, they do not need to be 
repeated for the Cycle 1, Day 1 time point.
9.5.4.2
Pregnancy Testing
All women who are being considered for participation in the study, and who are not 
surgically sterilized or postmenopausal, must be tested for pregnancy at screening and within 
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72 hours before the first dose of study treatment. Monthly testing should be conducted per 
local regulations. If a urine test is positive or not evaluable, a serum test will be required. 
Participants must be excluded/discontinued from study treatment in the event of a positive or 
borderline-positive test result.
9.6
9.7
Pharmacodynamics
Venous blood samples of MK-5890 will be collected for measurement of receptor 
availability and soluble receptor analyses. Sample collection, storage, and shipment 
instructions for PD samples will be provided in the Laboratory Manual.
If deemed appropriate, the Sponsor may eliminate the need for PD sampling and testing.
9.8
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9.9
9.10
Visit Requirements
Visit requirements are outlined in Section 2 – Schedule of Activities (SoA).  Specific 
procedure-related details are provided above in Section 9 – Study Assessments and 
Procedures.
9.10.1
Screening Period
During the screening period, potential participants will be evaluated to determine that they 
fulfill the entry requirements as set forth in Section 6.1 and Section 6.2. Screening 
procedures may be repeated after consultation with the Sponsor.
Documented informed consent must be obtained before performing any protocol-specific 
procedure. Results of a test performed prior to the participant signing consent as part of 
routine management are acceptable in lieu of a screening test if performed within the 
specified time frame. Screening procedures are to be completed within 28 days before the 
first dose of study treatment except for the following:

Safety laboratory tests are to be performed within 7 days before the first dose of study 
treatment.

For WOCBP, a urine or serum pregnancy test will be performed within 72 hours before
the first dose of study treatment. If urine pregnancy results cannot be confirmed as 
negative, a serum pregnancy test will be required (performed by the local study site 
laboratory).
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
Newly obtained tumor tissue is defined as tissue collected within 90 days before the first 
dose of study treatment. Archival tumor tissue is defined as tissue collected greater than 
90 days before the first dose of study treatment. The actual tumor sample is not required 
to be at the study site within the 28-day screening period.
9.10.2
Treatment Period
Visit requirements are outlined in Section 2 - Schedule of Activities (SoA). Specific 
procedure-related details are provided above in Section 9 - Study Assessments and 
Procedures.
9.10.3
Discontinued Participants Continuing to be Monitored in the Study
The End of Treatment visit should occur at the time study treatment is discontinued for any 
reason. Visit requirements are outlined in Section 2 - Schedule of Activities (SoA).
If the End of Treatment visit occurs 30 days from the last dose of study treatment, at the time
of the mandatory Safety Follow-Up visit, the End of Treatment visit procedures and any 
additional safety follow-up procedures should be performed.
Additional details regarding participant withdrawal and discontinuation are described in 
Section 8 - Discontinuation/Withdrawal Criteria.
9.10.3.1
Safety Follow-Up Visit
Participants will be required to return to the clinic for the Safety Follow-Up visit 
approximately 30 days after the last dose of study treatment or before initiating a new 
anticancer therapy, whichever occurs first. If the Safety Follow-Up visit occurs less than 
30 days after the last dose of study treatment, a subsequent follow-up phone call should be 
made 30 days after the last dose of study treatment to determine if any AEs occurred since 
the last study visit.
After treatment discontinuation, participants will be monitored for AEs for 30 days and SAEs 
for 90 days (30 days if the participant initiates new anticancer therapy). Participants with an 
ongoing AE at the time of treatment discontinuation will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up.
9.10.3.2
Imaging Follow-Up Visits
Participants who discontinue study treatment for reasons other than confirmed disease 
progression will have post-treatment follow-up imaging every 9 weeks for disease status until 
disease progression, initiating a new anticancer therapy, participant withdrawal of consent, 
pregnancy, becoming lost to follow-up, or death, whichever occurs first.
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9.10.3.3
Survival Follow-Up Visits
Participants, who experience confirmed disease progression or initiate a new anticancer 
therapy will be contacted by telephone approximately every 12 weeks for survival until 
participant withdrawal of consent, becoming lost to follow-up, death, or the end of the study, 
whichever occurs first.
9.10.4
Survival Status
To ensure current and complete survival data is available, updated survival status may be 
requested during the course of the study by the Sponsor. Upon Sponsor notification, all 
participants who do not/will not have a scheduled study visit or study contact during the 
Sponsor-defined time period will be contacted for their survival status (excluding participants 
who have a previously recorded death event in the collection tool).
10. STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategies and procedures for the primary and 
secondary analyses of the study. Exploratory and other non-confirmatory analyses will be 
outlined in a separate sSAP.
If, after the study has begun, changes are made to primary and/or secondary objectives, or the 
statistical methods related to those objectives, then the protocol will be amended (consistent 
with ICH Guideline E9). Changes to exploratory or other non-confirmatory analyses made 
after the protocol has been finalized, but prior to final database lock, will be documented in 
the sSAP as needed and referenced in the CSR for the study. Post hoc exploratory analyses 
will be clearly identified in the CSR.
10.1
Statistical Analysis Plan Summary
This section contains a brief summary of the statistical analyses for this study. Full details are
in the Statistical Analysis Plan (SAP), Section 10.2 through to Section 10.12.
Study Design 
Overview
Phase 1 study of MK-5890 monotherapy, MK-5890 in 
combination with pembrolizumab in participants with advanced 
solid tumors, MK-5890 in combination with pembrolizumab, 
pemetrexed, and carboplatin in participants with nonsquamous 
NSCLC, and MK-5890 in combination with pembrolizumab and 
nab-paclitaxel in participants with locally recurrent inoperable 
TNBC not previously treated with chemotherapy and which 
cannot be treated with curative intent or with not previously 
treated metastatic TNBC whose tumor PD-L1 CPS is less than 
10. The study applies a modified TPI design for dose escalation 
and confirmation of preliminary RPTDs, followed by an 
expansion phase with 3 efficacy cohorts (2 arms with TNBC and 
one arm with endometrial cancer).
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Analysis Populations
Safety: All-Subjects-as-Treated (ASaT)
PK: Per-Protocol (PP)
Efficacy: Full Analysis Set (FAS)
Primary Endpoint(s)
Safety in participants treated with MK-5890 monotherapy and 
MK-5890 in combination with pembrolizumab: Number 
(proportion) of participants with DLT(s), AE(s), and who 
discontinue study treatment due to AE(s)
Secondary Endpoints
PK parameters of MK-5890 when used as monotherapy, in 
combination with pembrolizumab, in combination with 
pembrolizumab, pemetrexed, and carboplatin, and in 
combination with pembrolizumab and nab-paclitaxel
ORR in participants treated with MK-5890 when used as
monotherapy, in combination with pembrolizumab, in 
combination with pembrolizumab and nab-paclitaxel in the 
dose expansion phase of the study
Safety in participants treated with MK-5890 in combination 
with pembrolizumab, pemetrexed, and carboplatin: Number 
(proportion) of participants with DLT(s), AE(s), and who 
discontinue study treatment due to AE(s)
Safety in participants treated with MK-5890 in combination 
with pembrolizumab and nab-paclitaxel: Number (proportion) 
of participants with DLT(s), AE(s), and who discontinue study 
treatment due to AE(s)
Statistical Methods 
for Efficacy/ 
Immunogenicity/ 
Pharmacokinetic 
Analyses
For the secondary endpoint of ORR as assessed by the 
investigator based on RECIST 1.1, the point estimate and 95% 
confidence interval (Clopper-Pearson interval) will be evaluated 
separately in participants in the dose expansion phase treated with 
MK-5890 as monotherapy (Arm 1a), MK-5890 in combination 
with pembrolizumab (Arms 2a, 2b, and 2c), MK-5890 in 
combination with pembrolizumab and nab-paclitaxel (Arm 4) 
using exact binomial distribution. Pairwise comparison will be 
conducted for ORR among Arm 1a (30 mg MK-5890 Q3W), 
Arm 2b (30 mg MK-5890 in combination with 200 mg 
pembrolizumab Q3W), and Arm 2c (30 mg MK-5890 in 
combination with 400 mg pembrolizumab Q6W) administered to 
participants with endometrial cancer using the Miettinen and
Nurminen method [Miettinen, O. and Nurminen, M. 1985]. The 
statistical methods for the tertiary/exploratory efficacy endpoints 
will be documented in a separate sSAP.
PK parameters of study treatments will be summarized by 
planned visit and time for each dose separately.
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Treatment
Assignment
All participants will be allocated to treatment centrally through 
IVRS/IWRS. Participants in the dose escalation and confirmation 
phase will be allocated by non-random assignment to receive 
MK-5890 monotherapy (Arm 1) or MK-5890 in combination 
with pembrolizumab (Arm 2). Participants in the dose escalation 
and confirmation phase with nonsquamous NSCLC enrolled as 
part of Amendment 02 will be allocated to receive MK-5890 in 
combination with pembrolizumab, pemetrexed, and carboplatin
(Arm 3). Participants in the dose expansion phase with TNBC 
will be allocated to receive 30 mg MK-5890 in combination with 
200 mg pembrolizumab Q3W (Arm 2a). Participants in the dose 
expansion phase with endometrial cancer will be randomized at a 
1:1:1 ratio to 30 mg MK-5890 Q3W (Arm 1a), 30 mg MK-5890
in combination with 200 mg pembrolizumab Q3W (Arm 2b), or 
30 mg MK-5890 in combination with 400 mg pembrolizumab
Q6W (Arm 2c). Participants in the dose expansion phase with 
TNBC enrolled as part of Amendment 03 will be allocated to 
30 mg MK-5890 in combination with 400 mg pembrolizumab 
Q6W and 100 mg/m2 nab-paclitaxel (Arm 4).  
Statistical Methods 
for Safety Analyses
Summary statistics will be provided for the safety endpoints as 
appropriate. In the dose escalation and confirmation phase (Arm 
1, Arm 2 and Arm 3) and the expansion phase (Arm 4), the 
pool-adjacent-violators algorithm [Ji, Y. and Wang, S.-J. 2013]
will be used to estimate the DLT rates across doses. The estimate 
of the DLT rate among participants treated at each tested dose 
level of MK-5890 and the 80% Bayesian credible intervals for the 
estimates will be provided.
Interim Analyses
In the dose escalation and confirmation phase (Arm 1, Arm 2 and 
Arm 3) and the expansion phase (Arm 4), data will be examined 
on a continuous basis to allow for dose-finding decisions using 
the mTPI design. In the dose expansion phase, the totality of the 
data will be examined once the first 15 participants with TNBC in 
Arm 2a are enrolled and have at least 1 post-baseline scan to 
decide whether or not to continue enrollment to 30 participants. 
In addition, the totality of the data will be examined once the first 
10 participants with endometrial cancer per treatment arm are 
enrolled and have at least 1 post-baseline scan to decide whether 
or not to continue enrollment to 20 participants in that arm. The 
totality of the data will be examined once the first 20 participants 
with TNBC in Arm 4 are enrolled and have at least 
1 post-baseline scan to decide whether or not to continue 
enrollment to 40 participants in that arm.  Other interim analyses
(eg, for efficacy) may be conducted to enable future study
planning at the Sponsor’s discretion.
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Multiplicity
No multiplicity adjustment is planned in this Phase 1 study.
Sample Size and 
Power
During the dose escalation and confirmation phase, 
approximately 72 participants are expected to be enrolled 
(62 participants in Arms 1 and 2, and 10 participants in Arm 3). 
The actual sample size will depend on the safety profile of 
MK-5890 in each treatment arm but is expected to be in line with 
a typical Phase 1 first-in-human oncology study. In the dose 
expansion phase, approximately 130 participants are expected to 
be enrolled, including 30 participants with TNBC in Arm 2a, 
60 participants with endometrial cancer (20 participants per arm) 
and 40 participants with TNBC in Arm 4. The actual sample size 
will depend on the safety profile of MK-5890 in combination 
with pembrolizumab and nab-paclitaxel (Arm 4) and efficacy 
profile in each arm. In total, approximately 202 participants will 
be used for study planning purposes. 
10.2
Responsibility for Analyses/In-House Blinding
The statistical analyses of the data obtained from this study will be the responsibility of the 
Clinical Biostatistics department of the Sponsor.
The study is open-label, ie, participants, investigators, and Sponsor personnel will be aware 
of participant treatment assignment after each participant is enrolled and treatment is 
assigned. Allocation to treatment will not be randomized.
10.3
Hypotheses/Estimation
Objectives of the study are outlined in Section 4 - Objectives/Hypotheses and Endpoints. No 
hypotheses are being tested in this study.
10.4
Analysis Endpoints
10.4.1
Efficacy/Immunogenicity/Pharmacokinetics Endpoints
ORR as assessed by the investigator based on RECISIT 1.1 for participants treated with 
MK-5890 monotherapy, MK-5890 in combination with pembrolizumab, and MK-5890 in 
combination with pembrolizumab and nab-paclitaxel in the dose expansion phase is a 
secondary endpoint in this study. All other efficacy endpoints described in Section 4 are 
tertiary/exploratory endpoints. A description of efficacy measures is provided in 
Section 9.2 - Efficacy Assessments.
Objective response rate is defined as the proportion of participants who have achieved 
confirmed CR or PR.
Progression-free survival is defined as the time from the first dose of study treatment to the 
first documented disease progression or death due to any cause, whichever occurs first.
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Overall survival is defined as the time from the first dose of study treatment to death due to 
any cause. Participants who do not die will be censored on the date of the last study 
assessment or contact.
Pharmacokinetic endpoints include serum concentrations of MK-5890 and pembrolizumab
and derived PK parameters.
10.4.2
Safety Endpoints
The primary safety endpoint is the number/proportion of participants with DLT(s), AE(s),
and who discontinue study treatment due to AE(s). In addition, safety and tolerability will be 
assessed by clinical review of all relevant parameters including laboratory tests and vital 
signs.
A description of safety measures is provided in Section 9.5 - Safety.
10.5
Analysis Populations
10.5.1
Safety Analysis Populations
The All-Subjects-as-Treated (ASaT) population will be used for the analysis of safety data in
this study. The ASaT population consists of all participants who received at least 1 dose of 
study treatment.
The DLT evaluable population will include ASaT participants who meet the criteria for DLT 
evaluability (eg, finished DLT evaluation period without a DLT or experienced a DLT in 
DLT evaluation period). See Section 7.2.2 for details.
At least 1 laboratory or vital sign measurement obtained subsequent to at least 1 dose of 
study treatment is required for inclusion in the analysis of each specific parameter. To assess 
change from baseline, a baseline measurement is also required.
Safety data from participants who experience disease progression in the monotherapy arms
and cross-over into the MK-5890 + pembrolizumab combination arm will be presented 
separately.
10.5.2
Pharmacokinetic Analysis Populations
The Per-Protocol (PP) population will be used for the analysis of PK and target engagement 
data in this study. The PP population consists of the subset of participants who complied with 
the protocol sufficiently to ensure that their data will be likely to exhibit the effects of 
treatment, according to the underlying scientific model. Compliance includes such 
considerations as exposure to treatment, availability of measurements, and the absence of 
major protocol violations. Any participants or data values excluded from the analyses will be 
identified in the CSR, along with the reasons for exclusion. At the end of the study, all 
participants who were compliant with the study procedures and have available data from at 
least 1 dose of study treatment may be included in the PP analysis dataset.
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10.5.3
Efficacy Analysis Populations
The Full Analysis Set (FAS) population will be used for the analyses of efficacy data in this 
study. The FAS consists of all participants with a baseline scan who demonstrated 
measurable disease by investigator assessment, and who were administered at least 1 dose of 
study treatment.
Efficacy data from participants who experience disease progression in the monotherapy arms
and cross-over into the MK-5890 + pembrolizumab combination arm will be presented 
separately.
10.6
Statistical Methods
This section describes the statistical methods that address the primary and secondary 
objectives. Methods related to tertiary/exploratory objectives will be described in the sSAP.
10.6.1
Statistical Methods for Efficacy Analysis
For the secondary endpoint of ORR as assessed by the investigator based on RECIST 1.1, the 
point estimate and 95% confidence interval will be evaluated separately in participants 
treated with MK-5890 monotherapy (Arm 1a), participants treated with MK-5890 in 
combination with pembrolizumab (Arms 2a, 2b, and 2c), and participants treated with 
MK-5890 in combination with pembrolizumab and nab-paclitaxel (Arm 4) using exact 
binomial distribution. Pairwise comparison will be conducted for ORR among participants 
with endometrial cancer treated in Arm 1a (30 mg MK-5890 Q3W), Arm 2b (30 mg
MK-5890 in combination with 200 mg pembrolizumab Q3W), and Arm 2c (30 mg MK-5890 
in combination with 400 mg pembrolizumab Q6W) using the Miettinen and Nurminen 
method [Miettinen, O. and Nurminen, M. 1985]. The statistical methods for the 
tertiary/exploratory efficacy endpoints will be documented in a separate sSAP.
10.6.2
Statistical Methods for Safety Analysis
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
DLTs, AEs, SAEs, laboratory tests, vital signs, ECG measurements, and physical 
examinations.
Adverse events will be summarized by counts and frequencies for each treatment arm and 
dose level. Laboratory tests, vital signs, and other safety endpoints will be summarized as 
appropriate (eg, counts, percentages).
In the dose escalation and confirmation phase (Arm 1, Arm 2 and Arm 3) and the dose 
expansion phase (Arm 4), DLTs will be listed and summarized by treatment arm and dose 
level. The pool-adjacent-violators algorithm [Ji, Y. and Wang, S.-J. 2013], which forces the 
DLT rate estimates to be non-decreasing with increasing dose levels and pools adjacent 
violators for weighted estimates by sample size, will be used to estimate the DLT rates across 
doses in each treatment arm. The estimate of the DLT rate among participants treated at each 
tested dose level of MK-5890 and the 80% Bayesian credible intervals based on a prior 
distribution of Beta (1,1) for the estimates will be provided.
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10.6.3
Summaries of Baseline Characteristics, Demographics, and Other Analyses
10.6.3.1
Demographic and Baseline Characteristics
Demographic variables, baseline characteristics, primary and secondary diagnoses, and prior 
and concomitant medications will be summarized.
10.6.3.2
10.7
Interim Analyses
In the dose escalation and confirmation phase (Arm 1, Arm 2 and Arm 3) and the dose 
expansion phase (Arm 4), data will be examined on a continuous basis to allow for 
dose-finding decisions using the mTPI design.
In the dose expansion phase, the totality of the data will be examined once the first 
15 participants with TNBC in Arm 2a are enrolled and have at least 1 post-baseline scan to 
decide whether or not to continue enrollment to 30 participants. 
 
 
 
In addition, the totality of the data will be examined once the first 10 participants with 
endometrial cancer per treatment arm are enrolled and have at least 1 post-baseline scan to 
decide whether or not to continue enrollment to 20 participants in that arm.
 
 
 
 
 
The totality of the data will be examined once the first 20 participants with TNBC in Arm 4
are enrolled and have at least 1 post-baseline scan to decide whether or not to continue 
enrollment to 40 participants in Arm 4
 
 
 
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Other interim analyses (eg, for efficacy) may be conducted to enable future study planning at 
the Sponsor’s discretion.
10.8
Multiplicity
There will be no multiplicity control in this study.
10.9
Sample Size and Power Calculations
During the dose escalation and confirmation phase, approximately 72 participants are 
expected to be enrolled (62 participants in Arms 1 and 2, and 10 participants in Arm 3). The 
actual sample size will depend on the safety profile of MK-5890 in each treatment arm but is 
expected to be in line with a typical Phase 1 first-in-human oncology study. In the dose 
expansion phase, approximately 130 participants are expected to be enrolled, including 
30 participants with TNBC in Arm 2a, 60 participants with endometrial cancer
(20 participants per arm) and 40 participants with TNBC in Arm 4. The actual sample size 
will depend on the safety profile of MK-5890 in combination with pembrolizumab and nab-
paclitaxel (Arm 4) and efficacy profile in each arm. In total, approximately 202 participants 
will be used for study planning purposes.
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10.10 Subgroup Analyses
Efficacy endpoints will be analyzed by arm, dose level, and tumor type. 
 
 
10.11 Compliance (Medication Adherence)
Compliance data for study treatment will be collected during the study. Any deviation from 
protocol-directed administration will be reported.
10.12 Extent of Exposure
The extent of exposure will be summarized as duration of treatment in cycles.
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11.
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12.
APPENDICES
12.1
Appendix 1: Study Governance Considerations
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
Code of Conduct for Interventional Clinical Trials
I. Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing, and reporting these trials 
in compliance with the highest ethical and scientific standards. Protection of participants in clinical trials is the 
overriding concern in the design and conduct of clinical trials. In all cases, MSD clinical trials will be conducted 
in compliance with local and/or national regulations (including all applicable data protection laws and 
regulations), and International Council for Harmonisation Good Clinical Practice (ICH-GCP), and also in 
accordance with the ethical principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or 
which are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the 
full control of MSD.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD 
may conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to 
determine patient preferences, etc.
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities 
and staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, 
sites are evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to 
successfully conduct the trial.
Where appropriate, and in accordance with regulatory authority guidance, MSD will make concerted efforts 
to raise awareness of clinical trial opportunities in various communities. MSD will seek to engage 
underrepresented groups and those disproportionately impacted by the disease under study. MSD will support 
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clinical trial investigators to enroll underrepresented groups and expand access to those who will ultimately 
use the products under investigation.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus 
source documentation according to standard operating procedures. Per MSD policies and procedures, if 
potential fraud, scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related 
Significant Quality Issues are reported, such matters are investigated. When necessary, appropriate corrective 
and/or preventative actions are defined and regulatory authorities and/or ethics review committees are 
notified.
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the
extent scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important 
to patients, physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather 
than hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be 
underpowered and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named 
authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in 
publications.
III. Participant Protection
A. Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority 
acceptance/authorization prior to implementation of the trial or amendment, in compliance with local and/or 
national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance 
with local and/or national regulations. Changes to the protocol that are required urgently to eliminate an 
immediate hazard and to protect participant safety may be enacted in anticipation of ethics committee approval. 
MSD will inform regulatory authorities of such new measures to protect participant safety, in compliance with 
local and/or national regulations.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At 
a minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is 
obtained. Participants may withdraw from an MSD trial at any time, without any influence on their access to, or 
receipt of, medical care that may otherwise be available to them.
C. Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible, as well as all 
applicable data protection rights. Unless required by law, only the investigator, Sponsor (or individuals acting on 
behalf of MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records 
that might identify the participant by name.
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D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an 
ethics committee.
IV. Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive. It is MSD’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of MSD trials. MSD does not pay incentives to 
enroll participants in its trials. However, when enrollment is particularly challenging, additional payments may be 
made to compensate for the time spent in extra recruiting efforts.
MSD does not pay for participant referrals. However, MSD may compensate referring physicians for time spent 
on chart review and medical evaluation to identify potentially eligible participants.
B. Clinical Research Funding
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may 
wish to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As 
noted above, all publications resulting from MSD trials will indicate MSD as a source of funding.
C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing the 
protocol, agree to support these ethical and scientific standards.
Financial Disclosure
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54).  It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required.  It is the investigator's/subinvestigator's 
responsibility to comply with any such request.  
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements.  
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes.  This may involve the 
transmission of information to countries that do not have laws protecting personal data.
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Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant names 
or any information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the institutional review board, ethics review committee (IRB/IEC) or similar 
or expert committee; affiliated institution and employees, only under an appropriate 
understanding of confidentiality with such board or committee, affiliated institution and 
employees.  Data generated by this study will be considered confidential by the investigator, 
except to the extent that it is included in a publication as provided in the Publications section 
of this protocol.
Confidentiality of Participant Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC, or regulatory authority representatives may consult and/or copy study documents in 
order to verify worksheet/case report form data.  By signing the consent form, the participant 
agrees to this process.  If study documents will be photocopied during the process of 
verifying worksheet/case report form information, the participant will be identified by unique 
code only; full names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all participant data used and 
disclosed in connection with this study in accordance with all applicable privacy laws, rules 
and regulations.
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC that reviews and 
approves this study.  The Sponsor is also required to document that each IRB/IEC meets 
regulatory and ICH GCP requirements by requesting and maintaining records of the names 
and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
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Publication Policy
The results of this study may be published or presented at scientific meetings. The sponsor 
will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement.
If publication activity is not directed by the sponsor, the investigator agrees to submit all 
manuscripts or abstracts to the sponsor before submission.  This allows the sponsor to protect 
proprietary information and to provide comments.  
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements.
Compliance with Study Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Amendments Act (FDAAA) of 2007 
and the European Medicines Agency (EMA) clinical trial Directive 2001/20/EC, the Sponsor 
of the study is solely responsible for determining whether the study and its results are subject
to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries.  MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD
entries are not limited to FDAAA or the EMA clinical trial directive mandated trials.  
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and site contact information.  
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries.
Compliance with Law, Audit and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of Good 
Clinical Practice (eg, International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use Good Clinical Practice: Consolidated 
Guideline and other generally accepted standards of good clinical practice); and all 
applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical study.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by MSD, is provided in this appendix 
under the Code of Conduct for Clinical Trials.
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The investigator agrees not to seek reimbursement from participants, their insurance 
providers or from government programs for procedures included as part of the study
reimbursed to the investigator by the Sponsor.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this study.
The Investigator agrees to provide the Sponsor with relevant information from inspection 
observations/findings to allow the Sponsor to assist in responding to any citations resulting 
from regulatory authority inspection, and will provide the Sponsor with a copy of the 
proposed response for consultation before submission to the regulatory authority. 
Persons debarred from conducting or working on clinical studies by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s studies. The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the study is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator or 
qualified designee is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
Study documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the study site upon request for inspection, 
copying, review and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities.  The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor or regulatory authority as a result of an audit or inspection to cure 
deficiencies in the study documentation and worksheets/case report forms.
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
Study monitors will perform ongoing source data review and verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that the 
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study is being conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICF, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Study and Site Closure
The sponsor or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable laws, 
regulations, and GCP. 
In the event the Sponsor prematurely terminates a particular study site, the Sponsor will 
promptly notify that study site’s IRB/IEC.
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12.2
 
CCI
CCI
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CCI
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CCI
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CCI
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CCI
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12.3
Appendix 3: Contraceptive Guidance and Pregnancy Testing
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below).
Women in the following categories are not considered WOCBP:
●
Premenarchal
●
Premenopausal female with 1 of the following:
○
Documented hysterectomy
○
Documented bilateral salpingectomy
○
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.
●
Postmenopausal female
○
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.
▪
A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). In the absence of 
12 months of amenorrhea, confirmation with two FSH measurements in the 
postmenopausal range is required.
○
Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment.
Contraception Requirements
Male Participants
Male participants with female partners of childbearing potential are eligible to participate if 
they agree to one of the following during the protocol-defined timeframe in Section 6.1:

Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
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
Use a male condom plus partner use of a contraceptive method with a failure rate of <1% 
per year as described in Table 15 when having penile-vaginal intercourse with a WOCBP
who is not currently pregnant.
o
The following are not acceptable methods of contraception:
▪
Periodic abstinence (calendar, symptothermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM).
▪
Male condom with cap, diaphragm, or sponge with spermicide.
▪
Male and female condom cannot be used together.
○
Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent 
from penile-vaginal intercourse or use a male condom during each episode of penile 
penetration.
Female Participants
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in 
Table 15 during the protocol-defined timeframe in Section 6.1.
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Table 15
Highly Effective Contraception Methods
Highly Effective Contraceptive Methods That Are User Dependenta
Failure rate of <1% per year when used consistently and correctly
●
Combined (estrogen and progestogen) hormonal contraceptionb, c
○
Oral
○
Intravaginal
○
Transdermal
○
Injectable
●
Progestogen only hormonal contraceptionb, c
○
Oral
○
Injectable
Highly Effective Methods That Have Low User Dependency
Failure rate of <1% per year when used consistently and correctly
●
Progestogen only contraceptive implantb, c 
●
Intrauterine hormone-releasing system (IUS)b
●
Intrauterine device (IUD)
●
Bilateral tubal occlusion
●
Vasectomized partner
A vasectomized partner is a highly effective contraception method provided that the partner is the 
sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used.
●
Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant.
Notes: 
Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants of clinical studies.
a) Typical-use failure rates are higher than perfect-use failure rates (ie, when used consistently and 
correctly).
b) If hormonal contraception efficacy is potentially decreased due to interaction with study treatment, 
condoms must be used in addition to the hormonal contraception during the treatment period and for 
at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of 
chemotherapeutic agents.
c) If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, 
acceptable hormonal contraceptives are limited to those that inhibit ovulation.
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Pregnancy Testing
WOCBP should only be included after a negative highly sensitive urine or serum pregnancy 
test.
Following initiation of study treatment additional pregnancy testing will be performed at 
monthly intervals during the treatment period and 120 days after the last dose of MK-5890 or 
pembrolizumab OR 180 days after the last dose of chemotherapeutic agents as required by 
local regulations.
Pregnancy testing will be performed whenever an expected menstrual cycle is missed or 
when pregnancy is otherwise suspected.
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12.4
Appendix 4: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definition of AE
AE Definition
●
An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study treatment, whether or not considered related 
to the study treatment.
●
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment.
●
NOTE: for purposes of AE definition, study treatment (also referred to as Sponsor’s 
product) includes any pharmaceutical product, biological product, vaccine, device, 
diagnostic agent or protocol specified procedure whether investigational (including 
placebo or active comparator product) or marketed, manufactured by, licensed by, 
provided by or distributed by the sponsor for human use in this study.
Events Meeting the AE Definition 
●
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, or are considered clinically significant in the 
medical and scientific judgment of the investigator.
●
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
●
New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study.
●
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
●
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. 
●
For all reports of overdose (whether accidental or intentional) with an associated adverse 
event, the AE term should reflect the clinical symptoms or abnormal test result.  An 
overdose of study treatment without any associated clinical symptoms or abnormal 
laboratory results is reported using the terminology “accidental or intentional overdose 
without adverse effect.”
●
Any new cancer (that is not a condition of the study).  Progression of the cancer under 
study is not considered a reportable event unless it results in hospitalization or death.
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Events NOT Meeting the AE Definition 
●
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
●
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
●
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
●
Surgery planned prior to informed consent to treat a pre-existing condition that has not 
worsened.
●
Refer to section 9.3.5 for protocol specific exceptions
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met 
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b. Is life-threatening
●
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
●
Hospitalization is defined as an inpatient admission, regardless of length of stay, even if 
the hospitalization is a precautionary measure for continued observation.  (Note: 
Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not a serious adverse event.  A pre-existing condition is a clinical condition 
that is diagnosed prior to the use of an MSD product and is documented in the patient’s
medical history.
d. Results in persistent or significant disability/incapacity
●
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.
●
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
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e.
Is a congenital anomaly/birth defect
●
in offspring of participant taking the product regardless of time to diagnosis
f.
Other important medical events:
●
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious.
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse.
Additional Events Reported in the Same Manner as SAE
Additional Events which require reporting in the same manner as SAE
●
In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Sponsor in the same 
timeframe as SAEs to meet certain local requirements. Therefore, these events are 
considered serious by the Sponsor for collection purposes.
●
Is a new cancer (that is not a condition of the study);
●
Is associated with an overdose.
Recording AE and SAE
AE and SAE Recording
●
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) related to 
the event.
●
The investigator will record all relevant AE/SAE information on the Adverse Event case 
report forms/worksheets at each examination.
●
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor in lieu of completion of the AE CRF page.
●
There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be blinded on the copies of the medical records before submission to the 
Sponsor.
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●
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
●
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
●
The investigator will make an assessment of intensity for each AE and SAE (and other 
reportable safety event) according to the NCI Common Terminology for Adverse Events 
(CTCAE), version 4.0 or later. Any adverse event which changes CTCAE grade over the 
course of a given episode will have each change of grade recorded on the adverse event 
case report forms/worksheets.
●
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated.
●
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL.
●
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL.
●
Grade 4: Life threatening consequences; urgent intervention indicated.
●
Grade 5: Death related to AE.
Assessment of Causality
●
Did the Sponsor's product cause the adverse event?
●
The determination of the likelihood that the Sponsor's product caused the adverse 
event will be provided by an investigator who is a qualified physician.  The 
investigator’s signed/dated initials on the source document or worksheet that supports 
the causality noted on the AE form, ensures that a medically qualified assessment of 
causality was done.  This initialed document must be retained for the required 
regulatory time frame.  The criteria below are intended as reference guidelines to 
assist the investigator in assessing the likelihood of a relationship between the test 
product and the adverse event based upon the available information
●
The following components are to be used to assess the relationship between the 
Sponsor's product and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the Sponsor's 
product caused the adverse event:
●
Exposure:  Is there evidence that the participant was actually exposed to the 
Sponsor's product such as:  reliable history, acceptable compliance assessment 
(pill count, diary, etc.), expected pharmacologic effect, or measurement of 
drug/metabolite in bodily specimen?
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●
Time Course:  Did the AE follow in a reasonable temporal sequence from 
administration of the Sponsor's product? Is the time of onset of the AE compatible 
with a drug-induced effect (applies to studies with investigational medicinal 
product)?
●
Likely Cause:  Is the AE not reasonably explained by another etiology such as 
underlying disease, other drug(s)/vaccine(s), or other host or environmental 
factors
●
Dechallenge: Was the Sponsor's product discontinued or 
dose/exposure/frequency reduced?
●
If yes, did the AE resolve or improve?
●
If yes, this is a positive dechallenge. 
●
If no, this is a negative dechallenge.
(Note:  This criterion is not applicable if:  (1) the AE resulted in death or 
permanent disability; (2) the AE resolved/improved despite continuation of the 
Sponsor's product; (3) the study is a single-dose drug study); or (4) Sponsor's 
product(s) is/are only used one time.)
●
Rechallenge:  Was the participant re-exposed to the Sponsor's product in this 
study?
●
If yes, did the AE recur or worsen?
●
If yes, this is a positive rechallenge. 
●
If no, this is a negative rechallenge.
(Note:  This criterion is not applicable if:  (1) the initial AE resulted in death or 
permanent disability, or (2) the study is a single-dose drug study); or (3) Sponsor's 
product(s) is/are used only one time.)
NOTE:  IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS 
SERIOUS AND WHICH MAY HAVE BEEN CAUSED BY THE SPONSOR'S PRODUCT, 
OR IF RE-EXPOSURE TO THE SPONSOR'S PRODUCT POSES ADDITIONAL 
POTENTIAL SIGNIFICANT RISK TO THE PARTICIPANT THEN THE 
RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR CLINICAL 
DIRECTOR AS PER DOSE MODIFICATION GUIDELINES IN THE PROTOCOL, AND 
IF REQUIRED, THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS 
COMMITTEE.
●
Consistency with Study treatment Profile:Is the clinical/pathological 
presentation of the AE consistent with previous knowledge regarding the 
Sponsor's product or drug class pharmacology or toxicology?
●
The assessment of relationship will be reported on the case report forms /worksheets by 
an investigator who is a qualified physician according to his/her best clinical judgment, 
including consideration of the above elements.
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●
Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a Sponsor's product relationship).
●
Yes, there is a reasonable possibility of Sponsor's product relationship:
There is evidence of exposure to the Sponsor's product.  The temporal sequence of the 
AE onset relative to the administration of the Sponsor's product is reasonable.  The 
AE is more likely explained by the Sponsor's product than by another cause. 
●
No, there is not a reasonable possibility of Sponsor's product relationship:
Participant did not receive the Sponsor's product OR temporal sequence of the AE 
onset relative to administration of the Sponsor's product is not reasonable OR the AE 
is more likely explained by another cause than the Sponsor’s product.  (Also entered 
for a participant with overdose without an associated AE.)
●
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
●
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to the Sponsor.
●
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.
●
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements
●
For studies in which multiple agents are administered as part of a combination regimen, 
the investigator may attribute each adverse event causality to the combination regimen or 
to a single agent of the combination.  In general, causality attribution should be assigned 
to the combination regimen (ie, to all agents in the regimen). However, causality 
attribution may be assigned to a single agent if in the investigator’s opinion, there is 
sufficient data to support full attribution of the adverse event to the single agent.
Follow-up of AE and SAE
●
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
●
New or updated information will be recorded in the CRF.
●
The investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information.
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Reporting of AE, SAE, and Other Reportable Safety Events to the Sponsor
AE, SAE, and Other Reportable Safety Event Reporting to Sponsor via Electronic Data 
Collection Tool
●
The primary mechanism for reporting to the Sponsor will be the electronic data collection 
(EDC) tool.  
●
Electronic reporting procedures can be found in the EDC data entry guidelines (or 
equivalent).
●
If the electronic system is unavailable for more than 24 hours, then the site will use 
the paper AE Reporting form.  
●
Reference section 9.3.1 – Time Period and Frequency for Collecting AE and SAE 
and Other Reportable Safety Event Information for reporting time requirements 
●
The site will enter the SAE data into the electronic system as soon as it becomes 
available.
●
After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.
●
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken off-
line, then the site can report this information on a paper SAE form or by telephone (see 
next section).
●
Contacts for SAE reporting can be found in the Investigator Trial File Binder (or 
equivalent).
SAE Reporting to the Sponsor via Paper CRF
●
If the electronic data collection tool is not operational, facsimile transmission or secure e-
mail of the SAE paper CRF is the preferred method to transmit this information to the 
Sponsor.
●
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.
●
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.
●
Contacts and instructions for SAE reporting and paper reporting procedures can be found 
in the Investigator Trial File Binder (or equivalent).
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12.5
Appendix 5: Clinical Laboratory Tests
•
The tests detailed in Table 16 will be performed by the local laboratory.
•
Protocol-specific requirements for inclusion and exclusion of participants are detailed in 
Section 6.1 and Section 6.2 of the protocol, respectively.
•
Investigators must document their review of each laboratory safety report.
•
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations.
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Table 16
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count 
RBC Indices:
• Mean Corpuscular Volume (MCV)
• Mean Corpuscular Hemoglobin (MCH)
• % Reticulocytes
White Blood Cell 
(WBC) Count with 
Differential:
• Neutrophils
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils
Red Blood Cell (RBC)
Count
Hemoglobin
Hematocrit
Chemistry
Sodium
Potassium
Chloride
Phosphorous
Calcium
Glucose
Bicarbonate / Carbon dioxide 
(CO2)1
Albumin 
Total Protein
Blood Urea Nitrogen 
(BUN)2
Creatinine (and measured or 
calculated [per institutional 
standard] creatinine clearance 
[CrCl], if creatinine is 
elevated above 1.5 times the 
upper limit of normal)3
Uric Acid
Alanine 
Aminotransferase 
(ALT) / Serum 
Glutamic-Pyruvic 
Transaminase (SGPT)
Aspartate 
Aminotransferase 
(AST) / Serum 
Glutamic-Oxaloacetic 
Transaminase (SGOT)
Alkaline Phosphatase
Total Bilirubin (and 
direct bilirubin, if 
total bilirubin is 
elevated above 
1.5 times the upper 
limit of normal)
Lactate Dehydrogenase 
(LDH)
Amylase
Lipase
Routine 
Urinalysis
• Specific Gravity
• pH, Glucose, Protein, Blood, Ketones by Dipstick
• Microscopic Examination (if blood or protein is abnormal)
Other Screening 
Tests
• International Normalized Ratio (INR)/Prothrombin Time (PT), Activated Partial Thromboplastin 
Time (aPTT) or Partial thromboplastin time (PTT)4
• Thyroid Function Testing (T4, T3, TSH)5
• Urine Pregnancy Test6
• Serum β-Human Chorionic Gonadotropin (β-hCG)6
• Follicle-Stimulating Hormone (FSH) and Estradiol (as needed in women of non-childbearing potential 
only)7
• Serology (human immunodeficiency virus [HIV] Type 1 and Type 2 antibodies; hepatitis B surface 
antigen [HBsAg]/hepatitis B virus antibody; and hepatitis C virus antibody ribonucleic acid (HCV 
RNA)/hepatitis C antibody)8
NOTES:
1.
If bicarbonate/CO2 is not done as part of standard of care in your region, these tests do not need to be performed.
2.
Blood urea nitrogen is preferred; if not available, urea may be tested.
3.
Glomerular filtration rate (GFR) can be used in place of CrCl.
4.
Coagulation factors (INR/PT and aPTT or PTT) should be tested as part of screening procedures for all participants. 
Any participant receiving anticoagulant therapy should have coagulation factors monitored closely throughout the 
study.
5.
Total T4 is preferred; if not available, free T4 may be tested. Total T3 is preferred; if not available, free T3 may be 
tested.
6.
Women of childbearing potential only. Urine pregnancy test is preferred. If the urine test is positive or cannot be 
confirmed as negative, a serum pregnancy test is required.
7.
In women <45 years of age, a high FSH in the postmenopausal range may be used to confirm a postmenopausal state 
in women not using hormonal contraception or hormone replacement therapy. In the absence of 12 months of 
amenorrhea, a single FSH measurement is insufficient.
8.
Testing is at the discretion of the investigator.
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12.6
Appendix 6: Country-Specific Requirements
Not applicable.
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12.7
Appendix 7: Description of the iRECIST Process for Assessment of Disease 
Progression
Assessment at Screening and Prior to RECIST 1.1 Progression
Until radiographic disease progression based on RECIST 1.1, there is no distinct iRECIST 
assessment.
Assessment and Decision at RECIST 1.1 Progression
For participants who show evidence of radiological disease progression by RECIST 1.1 as 
determined by the investigator, the investigator will decide whether or not to continue a 
participant on study treatment until repeat imaging is obtained (using iRECIST for 
participant management (see Table 12 and Figure 3). This decision by the investigator should 
be based on the participant’s overall clinical condition.
Clinical stability is defined as the following: 

Absence of symptoms and signs indicating clinically significant progression of disease

No decline in ECOG performance status

No requirements for intensified management, including increased analgesia, radiation, or 
other palliative care
Any participant deemed clinically unstable should be discontinued from study treatment at 
site-assessed first radiologic evidence of progressive disease, and is not required to have 
repeat tumor imaging for confirmation of disease progression by iRECIST.
If the investigator decides to continue treatment, the participant may continue to receive 
study treatment and the tumor assessment should be repeated 4 to 8 weeks later to confirm 
disease progression by iRECIST, per investigator assessment.
Tumor flare may manifest as any factor causing radiographic progression per RECIST 1.1, 
including:

Increase in the sum of diameters of target lesion(s) identified at baseline of ≥20% and 
≥5 mm from nadir;
Note: The iRECIST publication uses the terminology “sum of measurements”, but “sum 
of diameters” will be used in this protocol, consistent with the original RECIST 1.1 
terminology.

Unequivocal progression of non-target lesion(s) identified at baseline; or

Development of new lesion(s).
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iRECIST defines new response categories, including unconfirmed progressive disease
(iUPD) and confirmed progressive disease (iCPD). For purposes of iRECIST assessment, the 
first visit showing progression according to RECIST 1.1 will be assigned a visit (overall) 
response of iUPD, regardless of which factors caused the progression.
At this visit, target and non-target lesions identified at baseline by RECIST 1.1 will be 
assessed as usual.
New lesions will be classified as measurable or non-measurable, using the same size 
thresholds and rules as for baseline lesion assessment in RECIST 1.1. From measurable new 
lesions, up to 5 lesions total (up to 2 per organ), may be selected as New Lesions – Target. 
The sum of diameters of these lesions will be calculated, and kept distinct from the sum of 
diameters for target lesions at baseline. All other new lesions will be followed qualitatively 
as New Lesions – Non-Target.
Assessment at the Confirmatory Imaging Scan
On the confirmatory imaging scan, the participant will be classified as progression confirmed 
(with an overall response of iCPD), or as showing persistent unconfirmed progression (with 
an overall response of iUPD), or as showing disease stability or response (iSD/iPR/iCR).
Confirmation of Progression
Progression is considered confirmed, and the overall response will be iCPD, if ANY of the 
following occurs:

Any of the factors that were the basis for the initial iUPD show worsening

For target lesions, worsening is a further increase in the sum of diameters of ≥5 mm, 
compared to any prior iUPD time point

For non-target lesions, worsening is any significant growth in lesions overall, 
compared to a prior iUPD time point; this does not have to meet the “unequivocal” 
standard of RECIST 1.1

For new lesions, worsening is any of these:

An increase in the new lesion sum of diameters of ≥5 mm from a prior iUPD time 
point

Visible growth of new non-target lesions

The appearance of additional new lesions

Any new factor appears that would have triggered progressive disease by RECIST 1.1
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Persistent iUPD
Progression is considered not confirmed, and the overall response remains iUPD, if:

None of the progression-confirming factors identified above occurs; AND

The target lesion sum of diameters (initial target lesions) remains above the initial 
progressive disease threshold (by RECIST 1.1).
Additional imaging for confirmation should be scheduled 4 to 8 weeks from the imaging on 
which iUPD is seen. This may correspond to the next visit in the original visit schedule. The 
assessment of the subsequent confirmation imaging scan proceeds in an identical manner, 
with possible outcomes of iCPD, iUPD, or iSD/iPR/iCR.
Resolution of iUPD
Progression is considered not confirmed, and the overall response becomes iSD/iPR/iCR, if:

None of the progression-confirming factors identified above occurs; AND

The target lesion sum of diameters (initial target lesions) is not above the initial 
progressive disease threshold.
The response is classified as iSD or iPR (depending on the sum of diameters of the target 
lesions), or iCR if all lesions resolve.
In this case, the initial iUPD is considered to be pseudo-progression, and the level of 
suspicion for progression is “reset”. This means that the next visit that shows radiographic 
progression, whenever it occurs, is again classified as iUPD by iRECIST, and the 
confirmation process is repeated before a response of iCPD can be assigned.
Management Following the Confirmatory Imaging Scan
If repeat imaging does not confirm disease progression per iRECIST, as assessed by the 
investigator, and the participant continues to be clinically stable, study treatment may 
continue and follow the regular imaging schedule. If disease progression is confirmed, 
participants will be discontinued from study treatment.
NOTE: If a participant has confirmed radiographic progression (iCPD) as defined above, but 
the participant is achieving a clinically meaningful benefit, an exception to continue study 
treatment may be considered following consultation with the Sponsor. In this case, if study 
treatment is continued, tumor imaging should continue to be performed following the 
intervals outlined in Section 2.
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Detection of Progression at Visits after Pseudo-Progression Resolves
After resolution of pseudo-progression (ie, achievement of iSD/iPR/iCR), iUPD is indicated 
by any of the following events:

Target lesions

Sum of diameters reaches the progressive disease threshold (≥20% and ≥5 mm 
increase from nadir) either for the first time, or after resolution of previous 
pseudo-progression. The nadir is always the smallest sum of diameters seen during 
the entire study, either before or after an instance of pseudo-progression.

Non-target lesions

If non-target lesions have never shown unequivocal progression, their doing so for the 
first time results in iUPD.

If non-target lesions have shown previous unequivocal progression, and this 
progression has not resolved, iUPD results from any significant further growth of 
non-target lesions, taken as a whole.

New lesions

New lesions appear for the first time

Additional new lesions appear

Previously identified new target lesions show an increase of ≥5 mm in the new lesion 
sum of diameters, from the nadir value of that sum

Previously identified non-target lesions show any significant growth
If any of the events above occur, the overall response for that visit is iUPD, and the iUPD 
evaluation process (see ‘Assessment at the Confirmatory Imaging Scan’ above) is repeated. 
Progression must be confirmed before iCPD can occur.
The decision process is identical to the iUPD confirmation process for the initial progressive 
disease, with one exception: if new lesions occurred at a prior instance of iUPD, and at the 
confirmatory imaging the burden of new lesions has increased from its smallest value (for 
new target lesions, the sum of diameters is ≥5 mm increased from its nadir), then iUPD 
cannot resolve to iSD or iPR. It will remain iUPD until either a decrease in the new lesion 
burden allows resolution to iSD or iPR, or until a confirmatory factor causes iCPD.
Additional details about iRECIST are provided in the iRECIST publication [Seymour, L., et 
al 2017].
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Appendix 8: Abbreviations and Trademarks
Abbreviation/Term
Definition
1L
First-line
2L
Second-line
2L+
Two or more lines
ADA
Anti-drug antibody
AE
Adverse event
AJCC
American Joint Committee on Cancer
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
aPTT
Activated partial thromboplastin time
ASaT
All-Subjects-as-Treated
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
AUC
Area under the curve 
BCG
Bacillus Calmette–Guérin
β-hCG
β-human chorionic gonadotropin
CAP
College of American Pathologists
Cmax
Maximum concentration
Cmin
Minimum concentration
CNS
Central nervous system
CPS
Combined Positive Score
CR
Complete response
CRF
Case report form
CSF
Colony-stimulating factor
CSR
Clinical Study Report
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulating tumor DNA
CTLA-4
Cytotoxic T lymphocyte-associated antigen 4
D
De-escalate to the next lower dose
DILI
Drug-induced liver injury
DLT
Dose-limiting toxicity
DNA
Deoxyribonucleic acid
DU
Unacceptably toxic dose
ECG
Electrocardiogram
ECI
Event(s) of clinical interest
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
ELISA
Enzyme-linked immunoassay
EMA
European Medicines Agency
ESMO
European Society for Medical Oncology
EU
European Union
FAS
Full Analysis Set
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Abbreviation/Term
Definition
FBR
Future biomedical research
FDAA
Food and Drug Administration Amendments Act
FSH
Follicle-stimulating hormone
GCP
Good Clinical Practice
GFR
Glomerular filtration rate
GGT
Gamma glutamyl transferase
HBsAg
Hepatitis B surface antigen
HCV
Hepatitis C virus
HER-2
Human epidermal growth factor receptor 2
HIV
Human immunodeficiency virus
HR
Hazard ratio
HRT
Hormonal replacement therapy
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
iCPD
iRECIST confirmed progressive disease
IEC
Independent Ethics Committee
Ig
Immunoglobulin
IHC
Immunohistochemistry 
IL
Interleukin
IM
Intramuscular
INR
International normalized ratio
IO
Immuno-oncology
irAE
Immune-related adverse event
IRB
Institutional Review Board
iRECIST
Modified RECIST 1.1 for immune-based therapeutics
iSD
iRECIST stable disease
ITT
Intent To Treat
iUPD
iRECIST unconfirmed progressive disease
IV
Intravenous
IVD
In vitro diagnostic
IVRS
Interactive Voice Response System
IWRS
Integrated Web Response System
LDH
Lactate dehydrogenase
mAb
Monoclonal antibody
MASCC
Multinational Association of Supportive Care in Cancer
mBC
metastatic breast cancer
MRI
Magnetic resonance imaging
mRNA
Messenger ribonucleic acid
MSI
Microsatellite instability
MTD
Maximum tolerated dose
mTPI
modified toxicity probability interval
Nab-paclitaxel
Nanoparticle albumin-bound paclitaxel
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Abbreviation/Term
Definition
NCI
National Cancer Institute
NK
Natural killer
NOAEL
No observed adverse effect level
NSAID
Nonsteroidal anti-inflammatory drug
NSCLC
Non-small cell lung cancer
ORR
Objective response rate
OS
Overall survival
OTC
Over-the-counter
PBMC
Peripheral blood mononuclear cell
PD
Pharmacodynamic(s)
PD-1
Programmed cell death 1
PD-L1
Programmed cell death ligand 1
PD-L2
Programmed cell death ligand 2
PFS
Progression-free survival
PK
Pharmacokinetic(s)
PP
Per-Protocol
PR
Partial response
PT
Prothrombin time
PTT
Partial thromboplastin time
Q3W
Every 3 weeks
Q6W
Every 6 weeks
RECIST 1.1
Response Evaluation Criteria in Solid Tumors, version 1.1
RNA
Ribonucleic acid
RP2D
Recommended Phase 2 dose
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic-pyruvic transaminase
SNP
Single nucleotide polymorphism
SoA
Schedule of Activities
sSAP
Supplementary Statistical Analysis Plan
TCR
T cell receptor
TNBC
Triple-negative breast cancer
TNF
Tumor necrosis factor
TPI
Toxicity probability interval
TSH
Thyroid-stimulating hormone
ULN
Upper limit of normal
US FDA
United States Food and Drug Administration
WOCBP
Woman of childbearing potential
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MASCC 2016 Guidelines
Rolia F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the 
prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea 
and vomiting in advanced cancer patients. Ann Oncol (2016) 27 (suppl_5): v119-v133, 2016.
http://www.mascc.org/antiemetic-guidelines
Investigators may use local equivalent or more current guidelines, if available.
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