Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: BerGenBio ASA

CLINICAL STUDY PROTOCOL 
Protocol Title: 
Phase 1b/2a safety and tolerability study of bemcentinib with 
pembrolizumab/carboplatin/pemetrexed in subjects with untreated 
advanced or metastatic non-squamous non-small cell lung cancer 
(NSCLC) without/with a STK11 mutation. 
Protocol Number: BGBC016 
Substance: 
Bemcentinib 
Study Phase: 
Phase 1b/2a 
Short Title: 
A study to investigate the safety, tolerability, and preliminary 
anti-tumor activity of bemcentinib in combination with 
pembrolizumab plus pemetrexed and carboplatin in adult subjects 
with untreated non-squamous non-small cell lung cancer. 
Sponsor Name: 
BerGenBio ASA 
Legal Registered Address: 
Mollendalsbakken 9, 5009 Bergen, Norway 
Regulatory Agency Identifier Numbers: 
IND number: 
124645 
EudraCT: 
2019‐003806‐28 
Amendment no.: 
4 
Version: 
V3.0 
Scope: 
Global 
Approval Date: 
07-Jul-2023 
Replaces protocol version: 
V2.0 (Global), 07-Dec-22 
V2.0 (EU), 11-Jan-23 
V2.2 (France), 04-Jul-23 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that 
are privileged or confidential and may not be disclosed unless such disclosure is required 
by applicable laws and regulations or without prior written authorization from 
BerGenBio ASA (BGB). In any event, persons to whom the information is disclosed must 
be informed that the information is privileged or confidential and may not be further 
disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied to you, which is indicated as privileged or confidential. 

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Bemcentinib 
Clinical Study Protocol 
BGBC016 
Confidential 
V3.0 (Global), 07-Jul-2023 
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COMPLIANCE STATEMENT 
This study will be conducted in compliance with the protocol, the International Council 
on Harmonization of technical requirements for pharmaceuticals for human use (ICH) 
guidelines on Good Clinical Practice (GCP) E6(R2) (ICH, 2016), the Declaration of 
Helsinki (World Medical Association, 2013), and in accordance with local legal and 
regulatory requirements including the Clinical Trial Directive 2001/20/EC (European 
Parliament and Council of the European Union, 2001). 
Refer to Appendix 1 for compliance related to data protection. 
 
 
CONTACT DETAILS 
Contact details for the Medical Monitor, the Clinical Project Manager, and appointed 
Clinical Research Associates are provided to the study sites as a separate contact list. 

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Clinical Study Protocol 
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Document History 
Version 
Date 
Description of change 
1.0 
30-Jun-2022 
Original version 
2.0 
(Global) 
07-Dec-2022 
• 
Sponsor signature page was updated 
• 
An Investigator’s statement signature page was added 
• 
Pembrolizumab, carboplatin and pemetrexed defined as 
Investigational Medicinal Products (V2.0 Europe only) 
• 
Added bemcentinib 50 mg capsules 
• 
Added bemcentinib 125 mg as an alternative dose cohort 
• 
Updated eligibility criteria: 
o 
Inclusion criteria no. 1, 14: minor clarifications 
o 
Inclusion criteria no. 5: Treatment free interval 
update 
o 
Exclusion criteria no. 1, 2, 5, 6, 11, 13, 14, 22: 
Minor clarifications 
o 
Exclusion criteria no. 3: Prior malignancy free 
period updated 
o 
Exclusion criteria no. 4: Steroid free period 
updated 
o 
Exclusion criteria no. 12: Information regarding 
inclusion of HIV positive subjects updated 
• 
Definition of End of Study was updated 
• 
Clarifications were made to the descriptions of the 
follow-up periods following treatment discontinuation, 
i.e., safety follow-up period, progression free survival 
(PFS) follow-up period, survival follow-up 
• 
Clinical data from other bemcentinib studies were updated 
following the annual IB update 
• 
The risk benefit section was updated 
• 
To align the protocol to the Clinical Trial Regulation 
(Regulation (EU) No 536/2014), the following key updates 
were made: 
o 
Addition of relevant nonclinical data 
o 
Addition of relevant clinical data 
o 
The protocol synopsis was shortened 
Minor editorial changes to improve clarity and language have 
been made throughout the document 
2.0 
(Europe) 
11-Jan-2023 
2.1 
(France) 
2.2 
(France) 
3.0 
(Global) 
04-Apr-2023 
04-Jul-2023 
07-Jul-2023 
Note that updates in V2.1 (France), V2.2 (France) and V3.0 
(Global) overlap; updates specific to V3.0 Global have been 
identified in parentheses. 
• 
Included an updated study schema (Figure 1) (V3.0 
Global only) 
• 
Updated eligibility criteria: 
o 
Inclusion criterion no. 8: updated to include the 
required duration of contraception measures after 
the last dose of chemotherapeutic agents to align 
with the carboplatin and pemetrexed 
SmPCs/USPIs (US) 

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Clinical Study Protocol 
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V3.0 (Global), 07-Jul-2023 
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o 
Inclusion criterion no. 13: updated to define the 
acceptable screening QTcF interval separately for 
male and female subjects 
o 
Exclusion criterion no. 4: added “Subjects who 
have experienced an acute neurological event 
(e.g. intracranial or subarachnoid haemorrhage, 
stroke, intracranial trauma) within 6 months prior 
to study enrolment will be excluded” 
o 
Exclusion criterion no. 5: included “prior to first 
dose” in part b (V3.0 Global only), “or history of 
cardiomyopathy or left ventricular hypertrophy” in 
part c and “any conduction disorder within 
6 months prior to dosing” in part e 
o 
Exclusion criterion no. 10: updated to include 
“hereditary problem of galactose intolerance, 
LAPP-lactase deficiency or glucose-galactose 
malabsorption” 
o 
Exclusion criterion no. 16: updated to include “has 
a bleeding tumor” (Note: this was included as a 
new criterion in V2.1 France and included as part 
of criterion no. 16 in V3.0 Global) 
o 
Exclusion criterion no. 17: updated to included 
“stomach or duodenal ulcer” 
o 
Exclusion criterion no. 21: updated to include 
hypersensitivity to “pemetrexed, carboplatin or 
pembrolizumab” 
• 
Updated to include the required duration of contraception 
measures after the last dose of chemotherapeutic agents 
to align with the carboplatin and pemetrexed 
SmPCs/USPIs (US) 
• 
Updated to include risks of gonadal suppression with 
amenorrhea or azoospermia associated with carboplatin. 
Men are advised to seek advice on sperm preservation 
before starting therapy due to the possibility of 
irreversible infertility after treatment with carboplatin 
(V3.0 Global only) 
• 
Clarified that access to bemcentinib via an alternative 
access program or study is not applicable in France 
• 
Included a list of prohibited medications for study drugs in 
a new appendix 
• 
Pembrolizumab, carboplatin and pemetrexed defined as 
Investigational Medicinal Products in Europe and standard 
of care in the United States (V3.0 Global only) 
• 
Updated the details in Table 2 Study Medication Provided 
by Sponsor (V3.0 Global only) 
• 
Alimta (brand name) was replaced with pemetrexed in 
Table 3, and dose formulation updated for pemetrexed 
and carboplatin (V3.0 Global only) 
• 
Updated to include pemetrexed and carboplatin effects on 
ability to drive and operate machinery (V3.0 Global only) 
• 
Added a footnote to Table 10 to specify “diarrhea that 
requires hospitalization” 

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Clinical Study Protocol 
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V3.0 (Global), 07-Jul-2023 
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• 
Updated wording for dose limiting toxicities: 
o 
Thrombocytopenia previously captured under 
hematologic toxicity now captured as a separate 
toxicity; 
o 
Exceptions for Any Grade 3 or Grade 4 non- 
hematologic laboratory value revised to add that 
imaging will be performed at the investigator’s 
discretion to rule out pancreatitis for 
asymptomatic Grade 3 or Grade 4 amylase or 
lipase increase. 
• 
Clarified that the DSMB will recommend the bemcentinib 
dose for the phase 2a expansion cohort (V3.0 Global only) 
• 
Clarified in the protocol compliance section that the policy 
of BerGenBio is that no waivers will be issued (V3.0 
Global only) 

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Bemcentinib 
Clinical Study Protocol 
BGBC016 
Confidential 
V3.0 (Global), 07-Jul-2023 
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SPONSOR SIGNATORY PAGE 
The signatures below document the Sponsor approval of this clinical study protocol. 
Sponsor approval, BerGenBio ASA 
 
 
Name and Title 
 
 
 
 
 
 
 
 
 
Date 

BerGenBio ASA 
Bemcentinib 
Clinical Study Protocol 
BGBC016 
Confidential 
V3.0 (Global), 07-Jul-2023 
Page 7 of 111 
 
 
INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
Phase 1b/2a safety and tolerability study of bemcentinib with 
pembrolizumab/carboplatin/pemetrexed in subjects with untreated 
advanced or metastatic non-squamous non-small cell lung cancer 
(NSCLC) without/with a STK11 mutation 
Protocol Number: BGBC016 
Confidentiality, Good Clinical Practice and Compliance Statement: 
• I, the undersigned, have reviewed this protocol and amendment, including 
appendices, and I will conduct the study as described in compliance with this 
protocol and amendment, International Council for Harmonization of technical 
requirements for pharmaceuticals for human use (ICH) guidelines on Good Clinical 
Practice (GCP) E6(R2) and other relevant guidelines. All subjects will be informed 
comprehensively about the nature of the study and will give their written consent to 
participate before entry into the study. They will be informed that they may 
withdraw from the study at any time. I will use only the consent and information 
form approved by BerGenBio ASA (hereafter referred to as BGB) and the 
independent ethics committee (IEC)/institutional review board (IRB), for this study. 
• I am thoroughly familiar with the appropriate use of the study drug as described in 
this protocol and any other information provided by BGB including, but not limited 
to, the current Investigator’s Brochure. 
• I ensure that all persons or parties assisting me with the study are adequately 
qualified, trained, and informed about the study drug and of their delegated 
study-related duties and functions as described in the protocol. I ensure that source 
documents and study records that include all pertinent observations on each of the 
site’s study subjects will be attributable, legible, contemporaneous, original, 
accurate, and complete. 
• I understand that all information obtained during the conduct of the study with 
regard to the subject’s state of health will be regarded as confidential. No subjects 
personal identifying information will be disclosed. All subjects will be identified by 
assigned numbers on all case report forms, laboratory samples, or source 
documents forwarded to the Sponsor. Clinical information may be reviewed by the 
Sponsor or its agents or regulatory agencies. Should it be requested by government 
regulatory agencies, I will make available additional background data from my 
records, and where allowed, from the hospital or institution where the study was 
conducted. 
• I understand that the case report forms and other data pertinent to this study are 
the property of BGB and are confidential. I will supply BGB (or their delegates) with 
the study data in such a way that the patient cannot be personally identified. 
 
 
<Name> 
 
<Title> 
Investigator Signature 
<Institution> 
 
Date (DD-Mmm-YYYY) 

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Bemcentinib 
Clinical Study Protocol 
BGBC016 
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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ................................................................. 13 
1.1 
Synopsis ....................................................................................... 13 
1.2 
Flowchart ...................................................................................... 15 
2 
INTRODUCTION ......................................................................... 15 
2.1 
Study Rationale ............................................................................. 15 
2.1.1 
BGBC008 – second line NSCLC study combination with pembrolizumab 17 
2.1.2 
BGBIL005 – 2L NSCLC combination with docetaxel ............................. 17 
2.2 
Background ................................................................................... 18 
2.2.1 
Non-Small Cell Lung Cancer ............................................................ 18 
2.2.2 
Experience with Bemcentinib ........................................................... 19 
2.2.2.1 
Combination of Bemcentinib with Targeted Therapy and Chemotherapy19 
2.2.2.2 
Combination of Bemcentinib and Checkpoint Inhibition ........................ 19 
2.2.2.3 
Bemcentinib in STK11 Mutant NSCLC Model ....................................... 19 
2.2.2.4 
Combination of Bemcentinib, chemotherapy, and checkpoint inhibition.20 
2.2.3 
Overview of Clinical Studies ............................................................. 20 
2.2.3.1 
Exposure and Safety Evaluation ....................................................... 21 
2.2.3.2 
Safety Parameters .......................................................................... 21 
2.2.4 
Chemo-immunotherapy ................................................................... 22 
2.3 
Bemcentinib Benefit-Risk Assessment ............................................... 22 
3 
OBJECTIVES AND ENDPOINTS .................................................... 25 
4 
STUDY DESIGN ........................................................................... 26 
4.1 
Overall Design ............................................................................... 26 
4.2 
Number of Subjects ........................................................................ 27 
4.3 
Study Flow .................................................................................... 28 
4.4 
Definition of the End of Study .......................................................... 30 
4.5 
Scientific Rationale for Study Design ................................................. 30 
4.6 
Ethical considerations ..................................................................... 30 
4.7 
Justification for Dose ...................................................................... 30 
4.7.1 
Rationale for Bemcentinib Dose and Schedule Selection ....................... 30 
4.7.2 
Rationale for Chemo-Immunotherapy Dose ........................................ 32 
4.8 
End of Study and Study Closure Definition ......................................... 33 
5 
STUDY POPULATION .................................................................. 34 
5.1 
Inclusion Criteria ............................................................................ 34 
5.2 
Exclusion Criteria ........................................................................... 36 
5.3 
Screen Failures .............................................................................. 39 
6 
TREATMENTS .............................................................................. 40 
6.1 
Treatments Administered ................................................................ 40 
6.1.1 
Investigational Medicinal Product (Bemcentinib) ................................. 40 
6.1.2 
Investigational Medicinal Products (Europe)/Standard of Care (United 
States) (Pembrolizumab, Pemetrexed and Carboplatin) ....................... 40 
6.1.3 
Treatment Regimen ........................................................................ 42 
6.1.3.1 
Chemo-immunotherapy ................................................................... 43 
6.2 
Preparation/Handling/Storage/Accountability ...................................... 44 
6.2.1 
Preparation of Study Medication ....................................................... 45 
6.2.1.1 
Bemcentinib .................................................................................. 45 
6.2.1.2 
Pembrolizumab, carboplatin, and pemetrexed .................................... 45 
6.2.2 
Handling and Storage ..................................................................... 45 

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6.2.3 
Investigational Medicinal Products (Europe)/Bemcentinib (US) 
Accountability ................................................................................ 46 
6.2.4 
Return and Destruction of Investigational Medicinal Products 
(Europe)/Bemcentinib (US) ............................................................. 46 
6.2.5 
Reporting Product Complaints .......................................................... 47 
6.3 
Treatment Compliance .................................................................... 47 
6.3.1 
Bemcentinib .................................................................................. 47 
6.3.2 
All Clinical Study Medications ........................................................... 47 
6.4 
Concomitant Therapy...................................................................... 47 
6.4.1 
Premedication ................................................................................ 48 
6.5 
Prohibited Medication ...................................................................... 48 
6.6 
Effects on the Ability to Drive and Use Machines ................................. 48 
6.7 
Treatment Dose Modification ............................................................ 49 
6.8 
Treatment After the End of the Clinical Study ..................................... 56 
7 
TEMPORARY STUDY HALT/DISCONTINUATION OF STUDY 
MEDICATION AND SUBJECT WITHDRAWAL ................................ 57 
7.1 
Discontinuation of Study Medication .................................................. 57 
7.2 
Subject Withdrawal from the Clinical Study ........................................ 58 
7.2.1 
Replacement of subjects ................................................................. 58 
7.2.2 
Lost to Follow-up ........................................................................... 59 
7.3 
Clinical Study or Site Termination ..................................................... 59 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................... 60 
8.1 
Demographics and Other Baseline Characteristics ............................... 65 
8.1.1 
Demographics ................................................................................ 65 
8.1.2 
Medical History/Concomitant Illness .................................................. 65 
8.1.3 
Physical Examinations ..................................................................... 65 
8.1.4 
ECOG Performance Score ................................................................ 65 
8.1.5 
NSCLC Diagnosis ............................................................................ 65 
8.1.6 
Tumor Tissue Sample ..................................................................... 65 
8.1.7 
Liquid Biopsy NGS .......................................................................... 66 
8.2 
Efficacy Assessments ...................................................................... 66 
8.2.1 
Tumor Imaging .............................................................................. 66 
8.3 
Safety Assessments ........................................................................ 67 
8.3.1 
Body Weight and Height .................................................................. 67 
8.3.2 
Vital Signs ..................................................................................... 67 
8.3.3 
Electrocardiogram .......................................................................... 68 
8.3.4 
Echocardiography or MUGA .............................................................. 68 
8.3.5 
Clinical Safety Laboratory Assessments ............................................. 68 
8.3.6 
Dose Limiting Toxicities ................................................................... 69 
8.4 
Adverse Events and Serious Adverse Events ...................................... 70 
8.4.1 
Time Period and Frequency for Collecting AE and SAE Information ........ 71 
8.4.2 
Method of Detecting AEs and SAEs ................................................... 72 
8.4.3 
Follow-up of AEs and SAEs .............................................................. 72 
8.4.4 
Regulatory Reporting Requirements for SAEs ..................................... 73 
8.4.5 
Pregnancy ..................................................................................... 73 
8.5 
Treatment of Overdose ................................................................... 74 
8.6 
Pharmacokinetics ........................................................................... 74 
8.6.1 
Analysis Population ......................................................................... 74 
8.6.2 
Determination of Bemcentinib Concentration in Plasma ....................... 75 
8.6.3 
Pharmacokinetic Analysis ................................................................ 75 

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8.7 
Pharmacodynamics ......................................................................... 76 
8.8 
Genomics ...................................................................................... 76 
8.9 
Biomarkers .................................................................................... 76 
8.10 
Estimate of Total Blood Volume Collected .......................................... 77 
8.11 
Storage of Biological Samples .......................................................... 77 
9 
STATISTICAL CONSIDERATIONS ................................................ 78 
9.1 
Statistical Hypotheses ..................................................................... 78 
9.2 
Sample Size Determination .............................................................. 78 
9.3 
Analysis Sets ................................................................................. 78 
9.4 
Statistical Analyses......................................................................... 78 
9.4.1 
General Considerations ................................................................... 78 
9.4.2 
Primary Endpoints .......................................................................... 79 
9.4.3 
Secondary Endpoints ...................................................................... 79 
9.4.3.1 
Confirmatory Secondary Endpoints ................................................... 79 
9.4.3.2 
Supportive Secondary Endpoints ...................................................... 79 
9.4.4 
Exploratory Endpoints ..................................................................... 80 
9.4.5 
Other Safety Analyses .................................................................... 80 
9.4.6 
Other Analyses .............................................................................. 80 
9.5 
Interim Analyses ............................................................................ 80 
9.6 
Independent Data Safety Monitoring Board ........................................ 81 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ...................................................................... 82 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations .... 82 
10.1.1 
Regulatory and Ethical Considerations ............................................... 82 
10.1.2 
Financial Disclosure ........................................................................ 82 
10.1.3 
Liability and Insurance .................................................................... 82 
10.1.4 
Informed Consent Process ............................................................... 83 
10.1.5 
Data Protection .............................................................................. 84 
10.1.6 
Committees Structure ..................................................................... 84 
10.1.7 
Dissemination of Clinical Study Data ................................................. 84 
10.1.8 
Data Quality Assurance ................................................................... 85 
10.1.8.1 Data recording ............................................................................... 85 
10.1.8.2 Monitoring ..................................................................................... 85 
10.1.8.3 Protocol Compliance ....................................................................... 86 
10.1.8.4 Study Audit ................................................................................... 86 
10.1.8.5 Clinical Study Report ...................................................................... 86 
10.1.9 
Source Documents ......................................................................... 86 
10.1.10 
Study and Site Start ....................................................................... 87 
10.1.11 
Termination ................................................................................... 87 
10.1.12 
Responsibilities .............................................................................. 87 
10.1.13 
Publication Policy ........................................................................... 88 
10.2 
Appendix 2: Clinical Laboratory Tests ................................................ 89 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ................................................ 90 
10.3.1 
Definition of Adverse Events ............................................................ 90 
10.3.2 
Definition of Serious Adverse Events ................................................. 90 
10.3.3 
Recording and Follow-Up of AE and/or SAE ........................................ 91 
10.3.4 
Reporting of SAEs .......................................................................... 94 
10.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................... 94 

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10.5 
Appendix 5: Genomics .................................................................... 97 
10.6 
Appendix 6: Drugs that Prolong QT and Induce Torsades de Pointes ..... 99 
10.7 
Appendix 7: Prohibited Medications During the Study ........................ 103 
10.8 
Appendix 8: Eastern Cooperative Oncology Group Performance 
Status ........................................................................................ 103 
10.9 
Appendix 9: Abbreviations and Definitions of Terms .......................... 104 
11 
REFERENCES ............................................................................ 107 

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TABLE OF TABLES 
Table 1 
Objectives and Endpoints ...................................................................25 
Table 2 
Study Medication Provided by Sponsor ................................................40 
Table 3 
Chemo-Immunotherapy.....................................................................42 
Table 4 
Bemcentinib Daily Dose Modification for Potential Toxicities ....................50 
Table 5 
Dose Modification of Bemcentinib for Risk Management of QTcF 
Prolongation ....................................................................................51 
Table 6 
Recommended Dose Modification for Bemcentinib and CIT for Liver- 
Related Events .................................................................................52 
Table 7 
Dose Modifications for Chemo-Immunotherapy .....................................54 
Table 8 
Dose Modification Guidelines for Pembrolizumab Drug-Related AEs ..........54 
Table 9 
Recommended Dose Modifications for Key Pemetrexed and Carboplatin 
Hematological Toxicity ......................................................................56 
Table 10 
Recommended Dose Modifications for Pemetrexed and Carboplatin Non- 
Hematological Toxicity.......................................................................56 
Table 11 
Flowchart – Assessment and Visit Schedule ..........................................61 
Table 12 
Bemcentinib PK Sampling Timepoints and Permitted Windows ................75 
Table 13 
Plasma PK Parameters.......................................................................76 
Table 14 
Analysis Sets ...................................................................................78 
Table 15 
Protocol-Required Safety Laboratory Assessments ................................89 
Table 16 
Overview of Drugs that Prolong QT and Induce Torsades de Pointes ........99 
Table 17 
Prohibited Medications During the Study ............................................ 103 
 
 
TABLE OF FIGURES 
Figure 1 
Overall Study Design .................................................................... 27 
Figure 2 
Study flow for subject discontinuing CIT before or at the same time as 
bemcentinib ................................................................................. 29 
Figure 3 
Study flow for subject continuing CIT after End of Treatment (EoT); PFS 
follow-up ..................................................................................... 29 
Figure 4 
Non-Hematologic Grade ≥3 AEs pembrolizumab/platinum ..........................33 

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Phase 2a: To further assess the anti-tumor 
activity as well as the safety and 
pharmacokinetic profile of the combination 
bemcentinib with CIT when administered as 1L 
treatment. 
Phase 2a: The frequency and percentage of 
Adverse Events (AEs) and Serious Adverse 
Events (SAEs); assessment of safety 
laboratory parameters, vital signs, and 
electrocardiograms (ECGs). Response per 
RECIST 1.1: DCR, DOR, Progression free 
survival (PFS), Time to progression, OS, 
pharmacokinetic (PK) exposure. 
Study Design: 
This is an open-label, multi-center, phase 1b/2a clinical study to assess the safety, tolerability, 
and preliminary anti-tumor activity of bemcentinib in combination with CIT comprising 
pembrolizumab plus pemetrexed and carboplatin as 1L treatment in subjects with advanced 
(Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC without actionable mutations. 
In the phase 2a only subjects with a STK11m will be enrolled. All subjects will receive 
bemcentinib once daily in combination with CIT, which is administered on Day 1 of each 21-day 
treatment cycle. After the completion of 4 cycles of CIT + bemcentinib, study subjects will 
receive maintenance treatment with bemcentinib in combination with pemetrexed plus 
pembrolizumab. 
Phase 1b follows a standard 3+3 design: 3 subjects will receive bemcentinib + CIT at one of 
3 dose levels: Cohort 1=75 mg daily dose of bemcentinib; Cohort 2=100 mg daily dose of 
bemcentinib; or Cohort 3=150 mg daily dose of bemcentinib. An independent data safety 
monitoring board (DSMB) will review the safety data from each cohort at the end of the DLT 
assessment period (the first 21 days from C1D1 for each subject of each cohort) and based on 
overall safety and tolerability, the DSMB will recommend the bemcentinib dose for the phase 2a 
expansion. The clinical study consists of a screening period (up to 28 days), and a treatment 
period up to 24 months for each subject. All subjects will be followed for OS. 
Number of subjects: 
Phase 1b: 9-24 DLT-evaluable subjects. Phase 2a: 40 efficacy-evaluable subjects. Assuming a 
30% screening failure rate, up to 92 subjects will be screened to achieve the planned 
64 evaluable subjects. 
Patient population: 
Adult subjects with advanced or metastatic non-squamous NSCLC. 
Key inclusion: 
• 
Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) 
or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to 
curative therapy without actionable mutations. In phase 2a, the subjects must also have 
a STK11m. 
• 
Have not received prior systemic treatment for their advanced/metastatic NSCLC. 
• 
Have measurable disease per RECIST 1.1 as assessed by the Investigator. 
• 
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and adequate 
organ function. 
Main Assessments: 
The safety assessments include collection of AEs, SAEs, safety laboratory parameters, vital 
signs, and ECG changes. Efficacy will be assessed based on tumor scan evaluation by 
RECIST 1.1., chest, abdomen, and pelvis. Additionally, x-ray and bone scans, as well as imaging 
of other sites of disease will be used as appropriate. 
Ethical considerations and risk-benefit: 
As of July 2022, 543 subjects have been dosed with bemcentinib with diarrhea, nausea, and 
fatigue being the most commonly reported AEs; the reported liver AEs have resolved with 
steroid therapy. Subjects will be closely monitored, and the risk-benefit profile of bemcentinib is 
considered positive in subjects with advanced or metastatic disease with poor prognosis and 
limited treatment options. 

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1.2 
Flowchart 
The Flowchart displaying the assessments and visit schedule is available in Section 8, 
Table 11. 
2 
INTRODUCTION 
 
2.1 
Study Rationale 
 
Indication: 
Phase 1b: Previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) 
non-squamous NSCLC without actionable mutations (for phase 1b) 
Phase 2a: Previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) 
non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as 
identified by Next Generation Sequencing (NGS) and without actionable mutations. 
Rationale: 
Non-small cell lung cancer (NSCLC) is a life-threatening condition with a clear unmet 
need, particularly for subjects diagnosed with advanced or metastatic non-squamous 
NSCLC without a driver mutation, who represent the majority of NSCLC patients. Despite 
constant advances in therapy, the 5-year survival of NSCLC is approximately 20-30% 
(Min & Lee, 2021). 
Brain metastases are a common consequence of advanced lung cancer with currently no 
effective therapeutic options, due to a lack of actionable targets and a failure of systemic 
therapies to penetrate the blood-brain barrier (BBB). Studies have shown that the brain 
metastasis rate of NSCLC is approximately 10-20% (Bajard et al., 2004, Smith et al., 
2019, Waqar et al., 2018) with a higher incidence rate (approximately 30-50%) in 
patients with advanced NSCLC (Waqar et al., 2018, Ceresoli et al., 2002, Robnett et al., 
2001, Chen et al., 2007). 
Current developments for first-line (1L) treatment of NSCLC define a widening role for 
chemo-immunotherapy (CIT) regardless of programmed death-ligand 1 (PD-L1) status, 
with approval for the combination of platinum, pemetrexed, and pembrolizumab in 1L, 
which has become the standard of care (SOC) (Planchard et al., 2018, Ettinger et al., 
2022) in non–oncogene addicted NSCLC. However, despite an initial improvement in 
response rates and survival, the emergence of chemoresistance poses a significant 
obstacle to the management of NSCLC and highlights the unmet medical need in these 
patients (Min & Lee, 2021). 
Of the currently non-actionable mutations, STK11 mutations (STK11m) occur in ~20% 
of NSCLC subjects and recent evidence suggests that STK11m NSCLC patients have a 
minimal response to checkpoint inhibitors and to chemo-immunotherapy in the first line 
setting (Shire et al., 2020, Perez Parente et al., 2022). STK11 alterations drive an 
immunosuppressed tumor microenvironment (TME) by activation of AXL signaling. 
AXL suppresses anti-tumor innate immune cell responses, thus driving an 
immunosuppressive TME and promoting tumorigenicity and chemoresistance in tumor 
cells (Shire et al., 2020). AXL is a recognized driver of chemoresistance and AXL 
inhibition has been shown to prevent and reverse chemoresistance (Wilson et al., 2014, 
Wnuk-Lipinska et al., 2014, Wu et al., 2014, Brand et al., 2015, Wang et al., 2016, 
Lin et al., 2017, Ludwig et al., 2018). Moreover, AXL is a recognized driver for tumor 
metastases, with TAZ-AXL-ABL2 signaling axis promoting brain metastases in lung 

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cancer (Hoj et al., 2019) and AXL targeting by genetic silencing or pharmacological 
inhibition has been shown to prevent cancer metastasis in numerous mouse models 
(Auyez et al., 2021) An enhanced AXL expression in lung adenocarcinoma brain 
metastases relative to primary tumors was reported to be prognostic of poor survival 
outcomes (Wu et al., 2017). 
Analysis of patients with lung adenocarcinoma correlating gene expression to patient 
survival revealed that high expression of AXL, ABL2, or WWTR1 (TAZ) individually 
predicted reduced overall survival (OS) and progression free survival (PFS) (Hoj et al., 
2019). 
Importantly, AXL inhibition potentiated the efficacy of combined chemo-immunotherapy 
in models of NSCLC (Lee et al., 2022) as well as in models of breast cancer and 
melanoma (Dhakal et al., 2021, Dhakal et al., 2022). Enhanced T cell immunity was 
observed following AXL inhibition in the chemo-immunotherapy combination treatment 
in NSCLC models (Lee et al., 2022) and it was demonstrated that bemcentinib enhanced 
the Type 1 interferon (IFN) response following chemotherapy as well as reduced the 
tumor epithelial-mesenchymal transition (EMT) (Dhakal et al., 2021, Dhakal et al., 
2022). 
Analyses of subjects receiving pembrolizumab, ipilimumab/nivolumab, and 
durvalumab/tremelimumab have shown that STK11m subjects respond poorly to 
checkpoint inhibitors (CPIs) with a shorter PFS and OS as compared with STK11 
wild-type (STK11wt) subjects (Shire et al., 2020). 
Bemcentinib is a potent and highly selective, orally bioavailable, inhibitor of AXL tyrosine 
kinase. Bemcentinib potentiates the anti-tumorigenic activity of innate immune cells 
through regulation of myeloid suppressor activation, prevents and reverses aggressive 
EMT driven phenotypes in NSCLC cells, therefore potentiating the immune therapy 
through tumor EMT modulation, enhanced Type 1 IFN response and modulation of the 
immune cell landscape. 
Moreover, pharmacokinetic studies showed that bemcentinib crosses the BBB in mice 
(Meel et al., 2020) and readily distributes with higher concentrations in brain tumor 
issue in recurrent glioblastoma patients following oral administration (Nabors et al., 
2021). 
Recent preclinical data in syngeneic STK11m NSCLC mouse models refractory to 
pembrolizumab has demonstrated that the addition of bemcentinib to pembrolizumab in 
this setting re-instated checkpoint inhibition with strong synergistic responses to the 
combination in vivo (Li et al., 2022). It was observed that STK11m NSCLC mouse 
tumors drove AXL upregulation within the tumor microenvironment (rather than on the 
cancer cells) and AXL expression was identified on immunosuppressive macrophages and 
dendritic cells. This correlated with a more suppressive T cell composition in the tumor 
microenvironment. Furthermore, it was shown that bemcentinib, through inhibition of 
AXL expressed on the immunosuppressive dendritic cells, induced Type 1 IFN secretion 
and expansion of tumor associated TCF1+programmed cell death protein 1 (PD-1)+CD8 
T cells therapeutically sensitive to anti-PD-1 targeting and restoration of cytotoxic T cell 
antitumor response (Li et al., 2022). 
The doses of bemcentinib to be used in the clinical study have been selected to provide 
exposure levels of bemcentinib which are both safe and biologically active. As this is the 
first time bemcentinib is being dosed in combination with a chemotherapy doublet and 
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(75 mg) and will be escalated in a step-wise approach. Refer to Section 4.7 for a dose 
justification. 
In summary, based on supportive in vitro and in vivo pharmacology in NSCLC cells and 
animal models, as well as preliminary clinical data, there is a scientific rationale for the 
combination of bemcentinib with pembrolizumab plus pemetrexed and carboplatin in 
previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous 
NSCLC with no actionable mutations, including those with STK11m. 
2.1.1 
BGBC008 – second line NSCLC study combination with pembrolizumab 
BGBC008 (NCT03184571) is a Phase II, open-label, single-arm study to assess the 
efficacy and safety of bemcentinib in combination with pembrolizumab in subjects with 
previously treated, advanced adenocarcinoma of the lung. By 30 July 2022, 138 subjects 
have been enrolled, of which 99 have been assigned to treatment with 400 mg loading 
dose of bemcentinib for 3 days followed by a daily maintenance dose of 200 mg in 
combination with 200 mg pembrolizumab every 3 weeks. At the data cut-off, 95 subjects 
have discontinued bemcentinib treatment, 34 (34.3%) due to progression of disease, 
30 (30.3%) due to the Investigator’s decision, 23 (23.2%) due to adverse events (AEs), 
five have died (5.1%) and 3 (3.0%) due to withdrawal of consent. 
A total of 1327 treatment emergent AEs were reported in 101 subjects (73.2%). The 
most frequently reported AEs were diarrhea (29.7%), blood creatinine increased 
(21.7%), decreased appetite (21.7%), alanine aminotransferase (ALT) increased 
(21.0%) and aspartate aminotransferase (AST) increased (21.0%). An increased 
incidence of liver-related events had been observed in BGBC008 with the combination 
therapy of bemcentinib and pembrolizumab compared to monotherapy with bemcentinib 
or pembrolizumab alone. However, all reported events responded well to treatment with 
steroids and were reversible. This study is ongoing, and the safety data should therefore 
be considered as preliminary. 
An earlier report from six evaluable subjects with STK11m showed clinical benefit in 
three, when receiving the combination of bemcentinib and pembrolizumab, thus 
providing proof of concept and supporting the above in vivo preclinical data. In these six 
evaluable STK11m patients (four CPI-naïve and two CPI-progressed) the PFS ranges 
between 3.5 and >44 months and the OS between 10 months to >44 months. These 
initial observations compare favorably with the median progression free survival (mPFS) 
and median OS reported in second line (2L) STK11m NSCLC patients (2.2 months and 
6.3 months, respectively) (Shire et al., 2020) and that was indeed observed in those 
patients during their prior therapies. 
2.1.2 
BGBIL005 – 2L NSCLC combination with docetaxel 
Clinical data generated from an ongoing Phase Ib/II Investigator-led 2L NSCLC clinical 
study (BGBIL005 [NCT02922777]) of bemcentinib in combination with docetaxel showed 
encouraging clinical benefit when bemcentinib was given in combination with docetaxel 
with preliminary objective response rate (Ludwig et al., 2018) of 35%, which is higher 
than previously seen with docetaxel monotherapy or in combination with targeted 
therapies and provide proof of concept around the ability of bemcentinib to prevent and 
reverse chemoresistance (Bhalla et al., 2022). 

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2.2 
Background 
 
2.2.1 
Non-Small Cell Lung Cancer 
Lung cancer is the second most common cancer and the leading cause of cancer death in 
the USA. Approximately 247,270 new cases of lung cancer are estimated to occur in 
2020, with 130,340 male cases and 116,930 female cases (Siegel et al., 2020) Prior 
studies have reported that lung cancer resulted in more deaths than breast cancer, 
prostate cancer, colorectal cancer, and leukemia combined in men ≥40 years old and 
women ≥60 years old. With the introduction of screening guidelines and decrease in 
tobacco use, the mortality rate for lung cancer has recently decreased by 48% in males 
and 23% in females. Despite this decrease in mortality rate, approximately 
140,730 deaths are estimated to be secondary to lung cancer in 2020 (Siegel et al., 
2020). 
While progress has been made in the clinical management of early-stage NSCLC by 
establishing comprehensive, multi-modality treatment regimens, the prognosis for 
advanced disease has not improved substantially. Chemotherapy with a platinum-based 
doublet is SOC for patients with advanced NSCLC and pembrolizumab is considered the 
SOC for patients with advanced non-squamous NSCLC with a median overall survival 
(mOS) of 22.0 months (Gray et al., 2021). However, the emergence of chemoresistance 
poses a significant obstacle to the management of NSCLC and highlights the unmet 
medical need in these patients (Min & Lee, 2021). 
With the introduction of molecular testing, targeted therapy has improved clinical 
outcomes in a significant proportion of NSCLC patients with advanced disease and 
actionable mutations, however some mutations, such as STK11 mutation, in non- 
squamous NSCLC remain non-actionable mutations at present. STK11m is a tumor 
suppressor serine/threonine kinase that functions as master regulator of cell growth, 
metabolism, survival and polarity by interacting with downstream mediators. STK11m is 
present in up to ~20% of non-squamous NSCLC and is a recognized resistance 
mechanism for anti-PD-1/PD-L1 monotherapy with low response rates (2-3%) and 
limited clinical efficacy (mPFS 2-3 months). Moreover, recent evidence suggests that the 
levels of STK11m increase on immunotherapy treatment (Ricciuti et al., 2022). 
STK11m patients are characterized by reduced CD8+/PD-L1+ T cell infiltration, low 
PD-L1 expression, increased AXL expression on dendritic cells and relatively low level of 
actionable co-mutations (ALK, EGFR, etc.) (Li et al., 2022). 
Clinical data indicate that 1L NSCLC STK11m patients treated with PD-1/L1 blockade 
have shorter mPFS, mOS, and reduced response rates (objective response rate [ORR] 
33% vs 44%) compared to STK11wt NSCLC (Hellmann et al., 2018, Skoulidis et al., 
2018, Pore et al., 2021). Moreover, the addition of pembrolizumab to doublet 
chemotherapy in 1L STK11m NSCLC patients showed no added benefit [(mPFS 
4.8 months vs 4.3 months) and mOS (10.6 months vs 10.3 months)] compared to 
chemotherapy alone. This subgroup of patients, therefore, represents a high unmet 
medical need where the currently available therapies offer suboptimal benefit. 
Bemcentinib has the potential to restore immune checkpoint response and to delay 
chemoresistance. Encouraging data have been observed in clinical study BGBC008 
(NCT03184571) in 2L NSCLC treated with pembrolizumab and bemcentinib. In the six 
evaluable STK11 mutated patients (four CPI-naïve and two CPI-progressed) the PFS 
ranges between 3.5 and >44 months and the OS from 10 months to >44 months, which 
compared very favorably with the poor outcome reported in literature where mPFS and 

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mOS for 2L STK11m NSCLC patients following immune-oncology monotherapy was 
found to be 2.2 months and 6.3 months, respectively (Shire et al., 2020) and that was 
observed in those patients during their prior therapies. 
Based on the mode of action of bemcentinib and the encouraging data generated in 
2L NSCLC indicating that bemcentinib has the potential to both reverse chemoresistance 
in combination with chemotherapy as well as target immunosuppression in combination 
with immunotherapy, there is potential for bemcentinib to provide additional clinical 
benefit when combined with the chemo-immunotherapy currently administered as 1L 
treatment for NSCLC patients. 
2.2.2 
Experience with Bemcentinib 
Bemcentinib is a small molecule, orally bioavailable, highly specific inhibitor of AXL 
kinase. 
2.2.2.1 
Combination of Bemcentinib with Targeted Therapy and Chemotherapy 
Bemcentinib prevented chemoresistance to erlotinib in NSCLC HCC8277 (study 060-SR- 
324), sensitized A549 NSCLC cells to erlotinib (study 041-SR-324) and potentiated the 
anti-tumorigenic effect of docetaxel in the NSCLC H1299 (study 059-SR-324) xenograft 
models. Bemcentinib as a single agent and in combination with gemcitabine reduced 
spleen, small intestine and liver metastasis (study 054-SR-324; Ludwig et al., 2018) and 
enhanced the effect of gemcitabine in reducing primary tumor growth in pancreatic 
cancer models. There are several reports showing bemcentinib improved sensitivity to 
platinum and taxane in ovarian cancer (Quinn et al., 2019) restored paclitaxel sensitivity 
in uterine serous cancer (Palisoul et al., 2017) and helped overcome docetaxel 
resistance in advanced prostate cancer (Seymour et al., 2017). 
2.2.2.2 
Combination of Bemcentinib and Checkpoint Inhibition 
Bemcentinib has been shown to potentiate the activity of immune checkpoint blockade 
using antibodies targeting PD-1/programmed death-ligand 1 (PD-L1) and/or cytotoxic 
T-lymphocyte antigen-4 (CTLA-4) in syngeneic models of triple negative breast cancer 
(TNBC) (studies 102-SR-324; 153-SR-502P1MS6.2_Ver4; 348-TR-502; 368-TR-502) 
(Davidsen et al., 2019), lung cancer (study 179-SR-502P1MS10.2_Ver2), colorectal 
cancer (study 216-SR-502P1MS16) and melanoma (study 151-SR-502-P1MS3.3_Ver2), 
as well as breast cancer and glioblastoma (Sadahiro et al., 2018; Guo et al., 2017). 
Bemcentinib enhances immune checkpoint inhibition by influencing the tumor EMT 
status, by modulating the inflammatory cytokine profile and by modulating the presence 
and activation status of anti-tumorigenic immune cells in the tumors (Davidsen et al., 
2019; Ludwig et al., 2018) study 349-TR-502; study 179-SR-502P1MS10.2_Ver2; 
(Goyette et al., 2021; Li et al., 2022); study 422-TR-502). Moreover, bemcentinib 
increases the expression of surface receptors, thus facilitating tumor-NK and -CTL 
effector cell interaction and enhancing apoptosis (Terry et al., 2019). 
2.2.2.3 
Bemcentinib in STK11 Mutant NSCLC Model 
Mutations in Kirsten rat sarcoma virus (KRAS) and STK11/LKB1 have been reported to 
correlate with a more immunosuppressive TME, which may account for the limited 
response to anti-PD-1/PD-L1 treatment (Kadara et al., 2017; Koyama et al., 2016; 
Skoulidis et al., 2018). NSCLC mouse models with mutant KRAS/Tp53 knockout and 
STK11/LKB1 mutations (KPL) were used to determine if systemic AXL inhibition 
enhances the efficacy of anti-PD-1 therapy (Li et al., 2022). The combination of 

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bemcentinib with anti-PD-1 showed sustained control of tumor progression, indicating 
the therapeutic effect seen was dependent on the adaptive immune system (Li et al., 
2022). Mechanistically, bemcentinib facilitated increased type I IFN secretion and 
expansion of tumor-associated TCF1+ PD-1+ CD8 T cells resulting in restored 
therapeutic response to anti-PD-1 in both syngeneic immunocompetent mouse models 
and in humanized mice bearing STK11/LKB1 mutant NSCLC human tumor xenografts. 
2.2.2.4 
Combination of Bemcentinib, chemotherapy, and checkpoint inhibition 
In in vivo syngeneic mouse models of chemo-immunotherapy refractory tumor types, 
including those with low mutational burden or oncogenic drivers, bemcentinib 
potentiated the effect of immune checkpoint inhibitors in combination with 
chemotherapy and significantly enhanced survival (422-TR-502) (Dhakal et al., 2022). A 
recent paper showed that bemcentinib in combination with immune checkpoint therapy 
and chemotherapy produced the best anti-tumor effect in mouse models of lung 
adenocarcinoma and lung 1 cell carcinoma (Lee et al., 2022). 
For more details on the nonclinical data, refer to the bemcentinib Investigator’s brochure 
(IB) for a compilation of clinical and nonclinical data including pharmacokinetics (PK). 
2.2.3 
Overview of Clinical Studies 
To date, three company-Sponsored clinical studies have been completed - a phase 1 
(BGBC001) study in healthy volunteers, a phase 1/2 study in NSCLC (BGBC004) and a 
study (BGBC020) evaluating bemcentinib plus standard of care in subjects hospitalized 
with COVID-19. 
Previous and ongoing studies with bemcentinib, used a fasted dose of bemcentinib of 
400 mg loading dose and 200 mg maintenance dose. 
A phase 1 food and gastric effect study (BGBC018) has completed patient recruitment 
and has concluded and is in the final stages of reporting. 
Two phase 1b/2 company-Sponsored clinical studies (BGBC003 [NCT02488408] and 
BGBC008 [NCT03184571]) are currently ongoing in subjects with advanced cancers. 
One phase 2 clinical study (BGBC007 [NCT03184558]) evaluating bemcentinib in 
combination with pembrolizumab in patients with TNBC was terminated due to 
predefined futility. 
A further five Investigator-led studies (ILS) in the oncology setting are ongoing 
(BGBIL005 [NCT02922777], BGBIL006 [NCT02872259], BGBIL010, BGBIL011 
[NCT03654833], and BGBIL013 [NCT03965494]) and two studies (BGBIL009 and 
BGBIL019) have the clinical study report (CSR) under preparation (studies in advanced 
cancer and COVID-19). The ILS BGBIL006 is enrolling subjects with advanced 
non-resectable (Stage IIIc) or metastatic (Stage IV) melanoma. ILS BGBIL011 
(mesothelioma stratified therapy [MiST]) is enrolling subjects with relapsed malignant 
mesothelioma, and ILS BGBIL013 is enrolling subjects with recurrent glioblastoma. The 
ILS BGBIL009 (NCT03824080) has enrolled subjects with myelodysplastic syndrome 
(MDS) or acute myeloid leukemia (AML) that fail or are refractory to hypomethylating 
agent treatment (Gadgeel et al., 2020). 
The ILS BGBIL005 has enrolled subjects with previously treated advanced NSCLC and 
BGBIL010 has enrolled subjects with metastatic or recurrent pancreatic adenocarcinoma. 
There is also one ILS (BGBIL019), evaluating bemcentinib plus SOC in patients 
hospitalized with COVID-19 for which the final CSR is being developed. 

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Preliminary data from the ongoing phase 2 combination clinical study with 
pembrolizumab in previously treated NSCLC (BGBC008) is presented in Section 2.1. 
2.2.3.1 
Exposure and Safety Evaluation 
As per the cut-off date of 30 July 2022, 61 healthy subjects and 630 patients (AML, 
MDS, NSCLC, TNBC, melanoma, pancreatic cancer, glioblastoma, and COVID-19) have 
been included in the studies and 543 subjects in total have been dosed with bemcentinib 
in the seven company-Sponsored (BGBC001, BGBC003, BGBC004, BGBC007, BGBC008, 
BGBC018, and BGBC020; 405 patients included/348 patients dosed ) and the seven 
Investigator-led (BGBIL005, BGBIL006, BGBIL009, BGBIL010, BGBIL011, BGBIL013, 
and BGBIL019; 225 patients included/195 patients dosed) clinical studies (NCT numbers 
are provided in Section 2.2.3). 
Overall, the most commonly reported treatment emergent AEs were diarrhea (38.4%), 
nausea (27.2%), and fatigue (23.8%). A total of 13 deaths were reported (12 in the 
company-Sponsored bemcentinib clinical studies and 1 in the ILS) between 31 July 2021 
and 30 July 2022. Of the 12 deaths reported in the company-Sponsored studies, one 
occurred in clinical study BGBC003 (cause of death was unknown but possibly due to an 
infarction), 11 occurred in clinical study BGBC008. The one death reported in the ILS 
occurred in BGBIL010. The cause of death was not provided. 
In the company-Sponsored bemcentinib clinical studies up to the cut-off date, 52 deaths 
have been reported in the safety database as a result of serious AEs (SAEs). A 
comprehensive review of all deaths did not show any trends and the majority of the 
deaths were attributable to the disease under study. 
In the ILSs, 22 subjects have died due to SAEs (2 in BGBIL005, 3 in BGBIL006, 15 in 
BGBIL009, 1 in BGBIL010, and 1 in BGBIL013). Two deaths, one in BGBIL009 and 
another in BGBIL010 were assessed as related to study treatment. In total four deaths 
were assessed to be related to bemcentinib across all company-Sponsored and 
Investigator-led clinical studies. 
2.2.3.2 
Safety Parameters 
Overall, 106 patients in clinical studies BGBC003, BGBC004, BGBC007, and BGBC008 
were reported to have 195 events of QTcF (QT interval corrected for heart rate using 
Fridericia’s formula) prolongation, the majority of which were Common Terminology Criteria 
for Adverse Events (CTCAE) Grade 1 or 2 or not assessed as clinically significant. None of 
the patients experienced Grade 4 QTcF prolongation. It is of note the majority of the 
raised QTcF events were findings on scheduled electrocardiograms (ECGs). It is also 
important to note that there have been no cases of fatal arrhythmias reported in the 
bemcentinib development program to date. 
Low levels of magnesium (hypomagnesemia) were seen in a high proportion of patients 
in study BGBC008 (79.5% in Cohort A, 65.5% in Cohort B and 45.0% in Cohort C), 
however, it should be noted that the magnesium levels were elevated at baseline in 
most patients. 
Liver toxicity/elevated liver function test (LFT) were commonly reported events with the 
combination treatment of bemcentinib and pembrolizumab. Events of liver 
toxicity/elevated LFTs were reversible, and all events resolved when treated with 
corticosteroids. Most cases were reported as elevation of ALT and AST with normal 
bilirubin. Diagnoses of hepatotoxicity/immune hepatitis were made based on exclusion 
and none of the cases had confirmed liver damage from liver biopsies. Enhanced 

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monitoring of LFTs in the BGBC008 clinical study resulted in a reduction of the severity 
of the AEs reported with only a small number of patients reporting Grade 3 or Grade 4 
liver-related AEs. 
Preliminary safety data from the BGBC008 clinical study show that the combination 
treatment of bemcentinib (400 mg loading dose for 3 days followed by 200 mg daily as a 
maintenance dose) and pembrolizumab (200 mg every 3 weeks) in 2L NSCLC subjects 
had a favorable safety profile. 
There are several key safety events such as changes to liver enzymes and QTcF intervals 
that will be monitored closely in this clinical study to better characterize the risk-benefit 
profile of bemcentinib. 
2.2.4 
Chemo-immunotherapy 
In patients without targetable genetic alteration and no contraindication to the use of 
PD-1/PD-L1 inhibitors, immunotherapy, either as monotherapy or in combination, has 
become the SOC in the front-line setting for advanced squamous and non-squamous 
lung cancer (Ettinger et al., 2022). 
Pembrolizumab has demonstrated superior efficacy versus chemotherapy in untreated 
Stage IV NSCLC patients enrolled in KEYNOTE-024, a phase 3 randomized clinical study 
comparing single agent pembrolizumab against platinum chemotherapy. In this clinical 
study, patients with tumors expressing PDL-1 tumor proportion score (TPS) >50% 
demonstrated superior response rate with pembrolizumab monotherapy over 
chemotherapy (44.8% vs 27.8%, respectively), and OS (mOS 30.0 months vs 
14.2 months, respectively) (Reck et al., 2016). 
In KEYNOTE-189, a phase 3 clinical study in patients with non-squamous NSCLC 
regardless of TPS, study subjects were randomized to cisplatin or carboplatin plus 
pemetrexed with pembrolizumab or placebo followed by pemetrexed and pembrolizumab 
or placebo maintenance therapy (Gandhi et al., 2018). Overall survival was superior in 
the chemo-immunotherapy group for all subgroups of PD-L1 TPS, including patients with 
a score of less than 1%, a population for which single agent PD-1 and PD-L1 inhibition 
has a small benefit rate. In a recent update (Gray et al., 2021) the 4-year follow-up data 
from KEYNOTE-189 confirmed the superiority of the pembrolizumab-based combination. 
The median (95% CI) OS was 22.0 (19.5‒24.5) months with pembrolizumab plus 
pemetrexed-platinum vs 10.6 (8.7‒13.6) months with placebo plus pemetrexed- 
platinum (hazard ratio [HR], 0.60; 95% CI, 0.50‒0.72). The 3–year OS rate was 31.3% 
vs 17.4% with a median (95% CI) PFS of 9.0 (8.1‒10.4) months vs 4.9 (4.7‒5.5) 
months, respectively (HR,0.50; 95% CI, 0.41‒0.59). 
Based on the benefit observed in KEYNOTE-189, the combination of pembrolizumab plus 
platinum and pemetrexed is recommended in the international guidelines (i.e. European 
Society for Medical Oncology [ESMO], American Society of Clinical Oncology [ASCO], 
National Comprehensive Cancer Network [NCCN]) for the treatment of patients with 
previously untreated metastatic non-squamous NSCLC without sensitizing EGFR/ALK 
alterations, irrespective of PD-L1 expression (Planchard et al., 2018, Planchard et al., 
2020; Gadgeel et al., 2020; NCCN, 2022). 
2.3 
Bemcentinib Benefit-Risk Assessment 
Based on the emerging data (cut-off date of 30 July 2022), with 604 subjects exposed to 
bemcentinib either as monotherapy or in combination with other anticancer agents as 
discussed in Section 2.2.3, as well as the nonclinical toxicological and pharmacological 

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safety, the benefit-risk ratio is considered favorable and supports the development of 
bemcentinib for the treatment of cancers where there are limited treatment options or 
short life expectancy. 
Bemcentinib is a selective tyrosine kinase AXL inhibitor and there is a known class effect 
in relation to prolongation of QT/QTc. In the studies conducted so far, the majority of 
QT/QTcF prolongations were CTCAE Grade 1 or 2 or not assessed as clinically significant, 
identified during screening. None of the patients experienced Grade 4 QTcF prolongation. 
There have been no cases of fatal arrhythmias reported in the bemcentinib development 
program to date. The treatments that are given in combination with bemcentinib, 
pembrolizumab, pemetrexed, and carboplatin, are all well-known anti-neoplastic drugs 
that are widely used since many years, in different indications. New combinations always 
add a risk of synergetic effects to the safety profile of the individual drugs. Out of the 
604 subjects exposed to bemcentinib, 160 subjects with lung cancer have been treated 
with bemcentinib in combination with either pembrolizumab, targeted therapy (erlotinib) 
or chemotherapy (docetaxel). The combination with pembrolizumab showed an 
increased incidence of liver-related events compared to monotherapy with bemcentinib 
or pembrolizumab alone. However, all reported events responded well to treatment with 
steroids and were reversible. There were no reports of increased incidence of QT/QTcF 
prolongation with any NSCLC combination compared to bemcentinib monotherapy. 
Appropriate measures have been incorporated into this clinical study to safeguard 
subjects from potential risks and to closely monitor each subject throughout the clinical 
study, such as: 
• 
Close monitoring of subjects during the treatment period with 4 visits during the 
first treatment cycle as described in Table 11. 
• 
Exclusion of subjects with pre-existing cardiac conditions due to the potential risk 
associated with bemcentinib administration of prolongation of cardiac ventricular 
repolarization. Mitigation strategies such as: cardiac exclusion criteria 
(i.e. screening ECG with a mean QTcF interval ≤470ms [for women] and 
≤450 ms [for men]), specific monitoring requirements which includes ECG in 
triplicate, and instructions concerning dose modification if QTcF prolongation is 
observed, have been incorporated. 
• 
Diarrhea is a commonly reported event during bemcentinib treatment. All 
patients participating in the clinical study will be made aware of this potential 
reaction and will be instructed to contact their treating center at the first sign of 
increased stool frequency. Early treatment with loperamide or another 
anti-diarrheal agent is recommended. 
• 
Measures in the clinical study to address the risk of elevated LFTs include: 
o 
Frequent monitoring of LFTs to enable the treating physician to identify 
any deterioration at an early stage and take appropriate action. 
o 
Inclusion criteria to only allow participation of subjects with adequate 
hepatic function defined as: 
▪ 
Total bilirubin <1.5 ×ULN (<3 x ULN for participants with liver 
metastases). 
▪ 
AST (serum glutamic oxaloacetic transaminase [SGOT]) (AST 
[SGOT]) and ALT (serum glutamic pyruvic transaminase [SGPT]) 
<2.5 × ULN (<5 × ULN for participants with liver metastases). 

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• 
Dose modification guidance of bemcentinib for potential toxicities, Section 6.7. 
For inclusion of elderly subjects, the benefit/risk is also considered favorable. Inclusion 
of patients ≥65 years is based on emerging safety information from previous and 
ongoing studies, the thorough baseline/screening inclusion/exclusion criteria and safety 
monitoring in place for the study. 
Altogether, the risks associated with participating in this clinical study are considered to 
be outweighed by the potential clinical benefit for untreated advanced or metastatic 
non-squamous NSCLC patients enrolled in the clinical study. 

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4 
STUDY DESIGN 
 
4.1 
Overall Design 
This is an open-label, multi-center, phase 1b/2a clinical study to assess the safety, 
tolerability, and preliminary anti-tumor activity of bemcentinib in combination with CIT 
comprising pembrolizumab plus pemetrexed and carboplatin as 1L treatment in subjects 
with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC without 
actionable mutations, irrespective of PD-L1 status, with or without STK11m depending 
on the study phase. 
All subjects will receive bemcentinib once daily in combination with CIT, which is 
administered on Day 1 of each 21-day treatment cycle. 
• 
Phase 1b: Previously untreated locally advanced (Stage IIIb/IIIc)/metastatic 
(Stage IV) non-squamous NSCLC without actionable mutations. 
• 
Phase 2a: Previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) 
non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as 
identified by NGS and without actionable mutations. 
A schema of the study design is provided in Figure 1. A schedule of all study visits and 
procedures is provided in Table 11 and all study-related assessments are described in 
Section 8. 
Phase 1b follows a standard 3+3 design: 3 subjects will receive bemcentinib + CIT at 
one of 3 dose levels: Cohort 1=75 mg daily dose of bemcentinib; Cohort 2=100 mg daily 
dose of bemcentinib; or Cohort 3=150 mg daily dose of bemcentinib. An alternative dose 
level, i.e., Cohort 4, 125 mg, will be added in case of unacceptable toxicities in Cohort 3. 
An independent data safety monitoring board (DSMB) will be responsible for reviewing 
the safety data from each cohort at the end of the dose limiting toxicity (DLT) 
assessment period of each cohort and will provide recommendations to the Sponsor on 
dose cohort management. Further, based on overall tolerability, the DSMB will 
recommend the bemcentinib dose for the phase 2a expansion cohort. 
Subjects will take bemcentinib capsules daily and will continue until a reason for 
discontinuation has been met (see Section 7 for reasons for discontinuation) or for up to 
2 years, whichever occur first. Subjects will receive CIT on Day 1 of each 21-day 
treatment cycle for a maximum of 4 cycles. After completion of the 4 cycles of CIT, 
subjects will receive maintenance bemcentinib, pembrolizumab, and pemetrexed for up 
to 2 years. Any subjects still ongoing at 2 years after the start of treatment who 
continue to derive clinical benefit from the treatment, will be offered access to 
bemcentinib via an alternative access program or study (not applicable in France). 

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Figure 1 Overall Study Design 
 
Abbreviations: 1L=first line; Bem=bemcentinib; C=carboplatin; DC=doublet chemotherapy; DCR=disease 
control rate; DLT=dose limiting toxicity; DOR=duration of response; DSMB=data safety monitoring board; 
NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; Pem=pembrolizumab; 
P=pemetrexed; PFS=progression free survival; PK=pharmacokinetics; SOC=standard of care. 
The primary endpoint for phase 1b will be assessed after the first 21 days from C1D1 for 
each subject. To be DLT-evaluable, the subject must have received at least 80% of the 
bemcentinib dose (at least 17 of 21 days, with no more than 2 consecutive days of 
dosing missed) and completed evaluation for DLT in Cycle 1 or developed DLT during 
Cycle 1. 
The primary endpoint for phase 2a of the study is the ORR calculated from start of 
treatment (C1D1) to confirmation of response per Response Evaluation Criteria in Solid 
Tumors (RECIST) 1.1 at 6 and 12 months. 
In the phase 2a expansion there will be an interim analysis after 20 study subjects have 
completed 2 treatment cycles (no earlier than Day 42) with the purpose of identifying 
potential early efficacy signals. 
The clinical study consists of a screening period (up to 28 days), a treatment period (up 
to 24 months), a post-treatment safety follow-up period (30 days) and a survival 
follow-up phase for at least 2 years. For each subject, the expected duration of the 
clinical study when visits to the clinic are needed will be no more than 26 months. After 
the safety follow-up period and final study visit all subjects will be followed at 
≤3-monthly intervals to confirm their survival status following the final study visit until 
death unless they withdraw consent or are lost to follow-up, see Figure 2 and Figure 3. 
4.2 
Number of Subjects 
For phase 1b of the clinical study, 9 to 24 DLT-evaluable subjects (defined as subjects 
who have received at least 80% of the bemcentinib dose [at least 17 of 21 days, with no 
more than 2 consecutive days of dosing missed] and completed evaluation for DLT in 
Cycle 1 or developed DLT during Cycle 1) will be enrolled. 
For phase 2a of the clinical study, 40 efficacy-evaluable subjects (defined as subjects 
who do not discontinue study medication or withdraw from the clinical study before a 
post-baseline disease assessment has been completed) will be enrolled. 

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Assuming a 30% screening failure rate, approximately 92 subjects will be screened to 
achieve the planned 64 evaluable subjects. 
4.3 
Study Flow 
Screening period: 
The screening period (Day -28 to -1) has a maximum of 28 days and includes a single 
screening visit. 
Treatment period 
Following the screening period, eligible subjects will enter the open cohort: 
Phase 1b 
• 
Cohort 1: Bemcentinib 75 mg daily dose + CIT. 
• 
Cohort 2: Bemcentinib 100 mg daily dose + CIT. 
• 
Cohort 3: Bemcentinib 150 mg daily dose + CIT. 
• 
Alternative dose level: Cohort 4: Bemcentinib 125 mg daily dose + CIT. 
Phase 2a 
• 
Expansion cohort(s) at the recommended dose(s). 
The phase 2a expansion part of the study implements the dose(s) selected according to 
the methodology described in Figure 1. The selected dose(s) recommended for phase 2a 
will be the Maximum Tolerated Dose (MTD), (defined as the highest dose of a drug or 
treatment that does not cause unacceptable side effects), and, if applicable, the MTD-1 
dose, i.e., the dose level below MTD. 
The treatment period will continue for up to 24 months or until disease progression, 
withdrawal of consent, pregnancy, or introduction of other anticancer therapy. Any 
subjects still ongoing at 2 years after the start of treatment who continue to derive 
clinical benefit from the treatment, will be offered access to bemcentinib via an 
alternative access program or study (not applicable in France). 
Subjects who discontinue bemcentinib (for reasons other than disease progression) may 
continue CIT treatment, on study, for PFS follow-up see Figure 3, if this is considered in 
the best interest of the subject, as determined by the Investigator. The subject should 
continue according to the Flowchart of visits and assessments with the exception of 
ECGs. Once the subject is off bemcentinib treatment, one more ECG will be performed, 
at the next visit. 
The CIT treatment regimen is detailed in Section 6.1.2. 
Dose modifications will follow the standard guidelines for this regimen and will include 
dose reductions of bemcentinib for specified events (e.g., QTc events and liver function 
abnormalities). The dose reduction (and/or interruption or discontinuation) of 
bemcentinib will need to be performed as per guidance in the respective dose 
modification tables for toxicity, Section 6.7. 
Safety follow-up period 
All subjects will enter a safety follow-up period after bemcentinib discontinuation. The 
safety follow-up visit will occur 30 days after the last dose of bemcentinib, regardless of 
whether CIT is ongoing at that stage. 

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Disease progression follow-up 
Subjects who discontinue any of the 4 drugs in the treatment combination (but not all) 
for reasons other than “disease progression”, will continue to be followed up as 
described in Section 7.1 until disease progression, initiation of subsequent antineoplastic 
therapy, withdrawal of consent, death, or study closure, whichever occurs first. 
Survival follow-up 
All subjects will be followed for survival for at least 2 years or until withdrawal of 
consent, lost to follow-up, or death, whichever occurs first. The survival status should be 
assessed every third month by the method of choice of the Investigator, e.g., telephone 
contact or assessing the medical or official records, according to local practice. 
Patients lost to follow-up should be recorded as such on the electronic case report form 
(eCRF). For patients who are lost to follow-up, the Investigator should show "due 
diligence" by documenting in the source documents steps taken to contact the patient 
(e.g., dates of telephone calls, registered letters, etc.). 
 
 
Figure 2 Study flow for subject discontinuing CIT before or at the same time as 
bemcentinib 
 
 
 
Figure 3 Study flow for subject continuing CIT after End of Treatment (EoT); 
PFS follow-up 
 
All subsequent therapies should be recorded in the eCRF if the subject receives further 
treatment for NSCLC following the end of study visit. 

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4.4 
Definition of the End of Study 
• 
The overall End of Study and study closure is defined in Section 4.8. 
• 
For the individual subject, the study is considered completed when all phases of 
the clinical study including the Safety follow-up and the Survival follow-up phases 
are completed or until withdrawal of consent, lost to follow-up or death, 
whichever occurs first. 
4.5 
Scientific Rationale for Study Design 
The rationale for the clinical study is provided in Section 2.1. An uncontrolled, open-label 
design is chosen, as the purpose of the clinical study is to evaluate the safety and 
tolerability of bemcentinib in combination with CIT as 1L treatment in subjects with 
advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with no 
actionable mutations The design is regarded as scientifically justified and adheres to the 
ethical standards ensuring the rights, safety, and wellbeing of the subjects. 
The rationale for the CIT combination treatment is provided in Section 6.1.2. 
The combination of pembrolizumab plus pemetrexed and carboplatin has not previously 
been used in conjunction with bemcentinib in subjects (in any indication) and therefore a 
dose escalation design was chosen for the phase 1b part of the clinical study. 
4.6 
Ethical considerations 
Children, women who are pregnant, breastfeeding, or trying to become pregnant will not 
be enrolled in the clinical study. To participate in the clinical study, subjects (both male 
and female) of reproductive potential must be willing to practice highly effective 
methods of contraception throughout the clinical study and for an additional 4 months 
after the last dose of pembrolizumab, 6 months after the last dose of chemotherapeutic 
agents or 30 days after the last dose of bemcentinib whichever is the later. In addition, 
women of childbearing potential will have a pregnancy test done before, during, and 
after end-of treatment to ensure no fetuses are exposed to bemcentinib. 
In this clinical study, subjects will be treated with bemcentinib in addition to CIT. If 
subjects discontinue bemcentinib, they may continue CIT treatment at the discretion of 
the Investigator and hence will not be deprived from effective therapy. 
In accordance with the current version of the ICH-GCP guidelines, qualified medical 
personnel employed by Sponsor will be readily available to advise on study-related 
medical questions. Medical monitoring will be performed throughout the clinical study 
and safety data will be reviewed regularly by medically qualified staff by the Sponsor or 
designee to ensure that prompt action is taken, if needed, to maximize the safety of 
study subjects. Furthermore, an independent DSMB will be responsible for reviewing the 
safety data from each cohort and will provide recommendations to the Sponsor on the 
dose cohort management and recommend dose for the expansion cohort. 
4.7 
Justification for Dose 
 
4.7.1 
Rationale for Bemcentinib Dose and Schedule Selection 
The selection of the planned doses for the phase 1b/2a clinical study in 1L NSCLC 
patients has been centered around achieving a concentration at the target site that 
would engage and inhibit the biological target AXL with an acceptable benefit-risk profile. 
Bemcentinib is a competitive, reversible inhibitor of AXL with a Ki of 6 nM and a short 

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residence time of approximately 2 mins, so the minimum effective concentration to 
achieve 
 occupancy is approximately 24 nM, which is equivalent to a plasma 
total concentration of 
. 
A preliminary population PK model for bemcentinib has been developed from PK data 
derived from healthy- and oncology-subjects. The full dataset included 281 individual 
subjects (31 healthy subjects and 250 subjects with solid tumors and myeloid 
malignancies) containing 4149 PK sample results. This evaluation was based on single 
doses of bemcentinib of up to 
 in healthy subjects (Cmax range of 
 
) and repeat doses of up to 
 in oncology subjects with Cmax range of 
, all dosed in a fasted state. The PK variability was found to be 
 in the fasted state. 
Data generated from a food and gastric pH study (BGBC018) indicate that the Cmax and 
AUC are increased by 
 in the presence of food, whereas the variability in PK 
exposure was reduced by 
. 
Bemcentinib is a selective tyrosine kinase AXL inhibitor and there is a known class effect 
in relation to prolongation of QT/QTc. As a result of the known class effect the Sponsor 
has conducted extensive modelling of the relationship between exposure and QT/QTc 
change by using PK and ECG data from 59 healthy subjects and over 149 patients. It is 
understood that the QT/QTc change as measured by the 90% CI will start to change at 
or around 
. The Grade 3 AE incidence of QTcF following a loading dose of 
 for 3 days followed by 
 of bemcentinib in monotherapy was found to be 
, a reflection of the high variability in PK exposures in the fasted state. 
The increased exposure of bemcentinib (
) and reduced PK variability (
) 
when given with food provides the opportunity to generate exposures of bemcentinib 
similar to those generated in the fasted state at higher doses (approximately 
 
seen with the 400 mg loading/200 mg maintenance dose) but with reduced potential to 
cause QT/QTc prolongation. 
The modelled Cav at steady state generated by the doses of 75 mg, 100 mg, and 150 mg 
will be 
, respectively when dosed in the fed state. The 
pharmacokinetic-pharmacodynamic (PK-PD) analysis exploring the relationship of 
bemcentinib exposure with QTc change indicates that the concentrations of 
 
and 
 will produce a D-QT/QTc change of 19ms and 29ms, respectively, based 
on a 90% CI calculation. 
Bemcentinib has been safely dosed in combination with chemotherapies as well as 
immune-checkpoint inhibitors at multiple doses up to 400 mg loading for 3 days followed 
by 200 mg maintenance. As this is the first time bemcentinib is being dosed in 
combination with pembrolizumab plus the chemotherapy doublet pemetrexed and 
carboplatin, the initial dose of bemcentinib in the phase 1b will be at a daily dose of 
75 mg followed by a stepwise increase in dose utilizing a 3+3 approach to assess the 
safety of the combination. There will be no loading dose employed in this clinical study, 
in order to reduce any early potential AEs when combining bemcentinib with 
pembrolizumab plus pemetrexed and carboplatin. As bemcentinib will be dosed 
chronically in the 1L setting, it is not believed that the efficacy of bemcentinib 
(achievement of primary endpoints in phase 2a and secondary endpoints in phase 1b) 
will be affected by dropping the loading dose from the dosing regimen. A loading dose 
was originally used in prior bemcentinib clinical studies as bemcentinib has a long 
elimination half-life (steady state concentrations will be reached in 14 days when dosed 
without loading dose in this clinical study as opposed to 10 days with the loading dose). 

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4.7.2 
Rationale for Chemo-Immunotherapy Dose 
The US Food and Drug Administration (FDA)/EMA approved combination of 
pembrolizumab with pemetrexed and platinum as 1L treatment of patients with 
metastatic, non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations, has 
become the SOC. 
Clinical benefit of the combination was demonstrated by the KEYNOTE-189 clinical study 
(Gandhi et al., 2018) and the dosing regimen in the present clinical study is based on 
this. 
See Section 6.1.2 for a rationale using this CIT combination of medicinal products in the 
clinical study. 
All subjects will receive a) pembrolizumab at 200 mg Day 1 intravenous (IV); 
b) pemetrexed 500 mg/m2 body surface area (BSA) IV Day 1 and c) carboplatin (area 
under the concentration– time curve, 5 mg per milliliter per minute) IV after completion 
of the pemetrexed IV infusion Day 1 of a 21-day treatment cycle for a maximum of 
4 cycles. 
The safety of the combination of pemetrexed and platinum-based chemotherapy with 
pembrolizumab in 405 NSCLC patients was presented as a post-hoc analysis of the 
KEYNOTE-189 clinical study (Garon et al., 2021). A total of 334/405 (82.5%) subjects 
completed all 4 cycles of platinum-based chemotherapy. In summary, AEs Grade >3 
were reported in 272 patients (67.2%) with non-hematological AEs (nausea, vomiting, 
diarrhea, and asthenia) having a median time-to-onset within the first 4 cycles of 
treatment and a median time to resolution of <2 weeks (Figure 4). Thirty-seven patients 
(9%) discontinued pemetrexed or pembrolizumab during the first 4 cycles and 
31 (7.7%) of patients required platinum treatment discontinuation. 
It was concluded that the KEYNOTE-189 regimen is safe to use in clinical practice. 

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Figure 4 Non-Hematologic Grade ≥3 AEs pembrolizumab/platinum 
 
 
Time-to-Onset (Panel A) and Time-to-Resolution (Panel B) of Non-Hematologic Grade ≥3 AEs that Occurred in 
≥2 % of the All-Subjects-as Treated Population. Source: Garon et al., 2021 
Abbreviations: IQR=interquartile range; N/A=not applicable; Pem=pemetrexed; Pembro=pembrolizumab; 
Plat=platinum, Q1=quartile 1; Q3=quartile 3. 
 
4.8 
End of Study and Study Closure Definition 
• 
End of study is defined by the date of Last Subject Last Visit (LPLV) including 
the survival follow-up phase. 
• 
Study closure is defined by end of study and occurs when the database is locked 
and the CSR has been produced (excluding any CSR addendum). 

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5 
STUDY POPULATION 
In order to be eligible for this clinical study, the subjects must meet ALL the inclusion 
and NONE of the exclusion criteria as detailed below. 
5.1 
Inclusion Criteria 
To participate in this clinical study, the subject must fulfil ALL the below inclusion 
criteria: 
1. The subject (or legally acceptable representative, if applicable) must provide 
written informed consent for the study prior to any screening procedures. 
2. Be ≥18 years of age on the day of signing the informed consent. 
3. Have a histologically- or cytologically-confirmed diagnosis of advanced 
(Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC 
not amenable to curative therapy, irrespective of PD-L1 status and without 
actionable mutations (phase 1b). 
4. Have a histologically- or cytologically-confirmed diagnosis of advanced 
(Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC 
with STK11m, not amenable to curative therapy, irrespective of PD-L1 status and 
without actionable mutations (phase 2a). 
5. Participants who received prior neo-adjuvant or adjuvant/consolidation treatment 
(radiotherapy, chemotherapy, immunotherapy) or chemoradiotherapy with 
curative intent for non-metastatic disease must have experienced a 
treatment-free interval of at least 6 months since the last dose of chemotherapy, 
immunotherapy and/or radiotherapy before enrollment. 
6. Have measurable disease per RECIST 1.1 as assessed by the Investigator. 
Lesions situated in a previously irradiated area are considered measurable if 
progression has been demonstrated in such lesions. 
7. Have diagnostic/archival tumor tissue sample or newly obtained core or excisional 
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin 
embedded (FFPE) tissue blocks and/or slides with tumor will be requested. In the 
absence of adequate tumor material from the FFPE diagnostic block, fresh tissue 
biopsies will be requested. If it is not feasible to obtain a fresh biopsy, discuss 
with the Sponsor prior to excluding the subject from the study. 
Note: If submitting unstained cut slides, newly cut slides should be submitted to 
the testing laboratory within 14 days from the date slides are cut (details 
pertaining to tumor tissue submission can be found in the laboratory manual). 
8. Subjects (both male and female) of reproductive potential must be willing to 
practice highly effective methods of contraception throughout the clinical study 
and for 4 months after the last dose of pembrolizumab, 6 months after the last 
dose of chemotherapeutic agents or 30 days after the last dose of bemcentinib, 
whichever is later. 
9. A female subject is eligible to participate if she is not pregnant, not 
breastfeeding, and at least one of the following conditions applies: 
a. Note a woman of childbearing potential (WOCBP) if they have a history of 
surgical sterility (hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy) or evidence of post-menopausal status (no menses for 
12 months without any alternative medical cause – Follicle Stimulating 

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Hormone (FSH) level in the postmenopausal range may be used to confirm 
a post-menopausal state in women not using hormonal contraception or 
hormonal replacement therapy). 
b. A WOCBP must have a negative urine or serum pregnancy test within 
72 hours prior to the first dose of study treatment. If urine test is positive 
or cannot be confirmed as negative, a serum pregnancy test will be 
required. 
10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
11. Have a life expectancy of at least 3 months. 
12. Be able to swallow and tolerate oral medication. 
13. Have a screening 12-lead ECG (in triplicate) with a mean QTcF interval ≤470 ms 
(for women) and ≤450 ms (for men). 
14. Have adequate organ function as defined in the table overleaf. 

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System 
Laboratory value 
Hematological 
Absolute neutrophil count 
≥1500/µL 
Platelets 
≥100 000/µL 
Hemoglobin 
≥9.0 g/dL or ≥5.6 mmol/L1 
Renal 
Measured or calculated2 creatinine 
clearance (eGFR can also be used in 
place of creatinine or CrCl) 
Calculated creatinine clearance ≥45 mL/min (by 
Cockcroft Gault formula) 
Hepatic 
Total bilirubin 
<1.5 × ULN (<3 x ULN for subjects with liver 
metastases) 
AST (SGOT) and ALT (SGPT) 
<2.5 × ULN (<5 × ULN for subjects with liver 
metastases) 
Coagulation (Optional) 
International normalized ratio (INR) 
OR prothrombin time (PT) 
Activated partial thromboplastin 
time (aPTT) 
≤1.5 × ULN unless subject is receiving 
anticoagulant therapy as long as PT or aPTT is 
within therapeutic range of intended use of 
anticoagulants 
Abbreviations: ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); 
AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); 
CrCl=creatinine clearance; DLT=dose limiting toxicity; DSMB=data safety monitoring board; 
GFR=glomerular filtration rate; PT=prothrombin time; ULN=upper limit of normal. 
1Criteria must be met without packed red blood cell transfusion within one week of screening. 
Subjects can be on stable dose of erythropoietin (≥approximately 3 months). 
2CrCl should be calculated by Cockcroft Gault formula. 
Notes: 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. 
Note: AST and ALT may have their limits increased in cases of liver metastases; however enrolling 
subjects with elevated values at baseline may be inviting DLTs, therefore this should be discussed 
with the DSMB. 
 
 
5.2 
Exclusion Criteria 
A subject will not be eligible for enrollment into the clinical study if they meet ANY of the 
following exclusion criteria: 
1. Has received any prior chemotherapy or biological therapy for advanced 
(Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC. 
2. Has any actionable mutation that is considered targetable with first-line 
treatment. 
3. Has a known history of prior malignancy except if the subject has undergone 
potentially curative therapy with no evidence of disease recurrence for 3 years 
since initiation of that therapy. 
Note: The time requirement for no evidence of disease for 3 years does not apply 

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to the NSCLC tumor for which a subject is enrolled in the clinical study. The time 
requirement also does not apply to subjects who underwent successful definitive 
resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous 
cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. 
4. Has known active central nervous system (CNS) metastases and/or 
carcinomatous meningitis. Subjects with previously treated brain metastases may 
participate, provided they are radiologically stable, i.e. without evidence of 
progression for at least 2 weeks and have no evidence of new or enlarging brain 
metastases and are off steroids 7 days prior to dosing with study medication. 
Stable brain metastases by this definition should be established prior to the first 
dose of study medication. Subjects with asymptomatic brain metastases (i.e. no 
neurological symptoms, no requirements for corticosteroids, and no lesion 
>1.5 cm) may participate but will require regular imaging of the brain as a site of 
disease. Subjects who have experienced an acute neurological event 
(e.g. intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) 
within 6 months prior to study enrolment will be excluded. 
5. History of the following cardiac conditions: 
a. Congestive cardiac failure of >Grade II severity according to the New York 
Heart Association (NYHA) or resistant or inadequately treated heart 
failure. 
b. Ischemic cardiac event including myocardial infarction prior to first dose or 
hospitalization for unstable angina within 3 months prior to first dose. 
c. Abnormal left ventricular ejection fraction on echocardiography or 
multi-gated acquisition scan (MUGA) (less than the lower limit of normal 
for a subject of that age at the treating institution or <45%, whichever is 
lower), or history of cardiomyopathy or left ventricular hypertrophy. 
d. Uncontrolled cardiac disease, including unstable angina, uncontrolled 
hypertension (i.e., sustained systolic blood pressure (BP) >160 mmHg or 
diastolic BP >90 mmHg), or need to change medication due to lack of 
disease control within 12 weeks prior to the provision of consent. 
e. History or presence of sustained bradycardia (≤55 bpm) or history of 
symptomatic bradycardia, left bundle branch block, cardiac pacemaker, 
significant arrhythmias or any conduction disorder within 6 months prior 
to dosing as defined by the need for treatment. 
f. 
Family history of long QTc syndrome or ventricular arrhythmias; personal 
history of long QTc syndrome or previous drug induced QTc prolongation 
of at least Grade 3 (QTc >500 ms). 
g. Presence of any other risk factors that increase the risk of QTc 
prolongation, specifically, hypokalemia or hypomagnesemia (if corrected 
the subject may be enrolled) or inadequately treated hypothyroidism 
(defined as thyroid stimulating hormone [TSH] below the expected range). 
h. Current treatment with any agent known to cause QT prolongation and 
have a risk for Torsades de pointes (TdP), which cannot be discontinued at 
least 5 and ½ half-lives or 2 weeks prior to the first dose of study 
treatment, with the exception of antiemetics (e.g. ondansetron) which 
may be required. Please see https://crediblemeds.org for a list of 

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medications with known TdP risk that need to be excluded (also included 
in Appendix 6). 
6. Received radiation therapy for brain metastasis within 2 weeks prior to starting 
study treatment or has not recovered (i.e., ≤Grade 1 at baseline) from AEs due 
to a previous radiation therapy. 
7. Major surgery within 28 days prior to start of study treatment and failure to have 
recovered adequately from the complications of the surgery/intervention prior to 
the first dose of study treatment. 
Note: Major surgery does not include procedures for insertion of venous catheters 
or biopsies. 
8. Has had an allogeneic tissue/solid organ transplant or an allogeneic 
hematopoietic stem cell transplantation (alloHSCT) within the last 5 years. 
Note: Subjects who had an alloHSCT >5 years ago are eligible only if there are no 
symptoms of Graft vs Host Disease (GVHD). 
9. Has an active autoimmune disease that has required systemic treatment in the 
past 2 years (i.e., required use of disease modifying agents, corticosteroids, or 
immunosuppressive drugs). 
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy [no >10 mg prednisolone or equivalent] for adrenal or 
pituitary insufficiency, etc.) or inhaled corticosteroids (e.g. for asthma) are not 
considered a form of systemic treatment. 
10. Has a known lactose intolerance, hereditary problem of galactose intolerance, 
LAPP-lactase deficiency or glucose-galactose malabsorption. 
11. Is currently participating and receiving another study therapy or have 
participated in a clinical study with an investigational medicinal agent and 
received study therapy or used an investigational device within 28 days or within 
5 half-lives, whichever is longer, of the first dose of study treatment. 
12. Subjects with known human immunodeficiency virus (HIV) infection are eligible if 
they have a CD4+ T cell (CD4+) counts ≥350 cells/uL; in addition, subjects on 
established anti-retroviral treatment for at least 4 weeks who have an HIV viral 
load less than 400 copies/mL prior to enrollment may also be eligible. No HIV 
testing is required, unless mandated by the local health authority. Subjects on 
atazanavir or tenofovir therapy must be excluded due to the risk of drug-drug 
interactions. 
13. Has known active Hepatitis B infection (e.g., Hepatitis B surface antigen [HbsAg] 
reactive and/or detectable Hepatitis B virus [HBV] deoxyribonucleic acid [DNA] 
viral load) or Hepatitis C (e.g., Hepatitis C virus (HCV) ribonucleic acid [RNA] 
[qualitative] is detected). 
Note: Subjects with a history of hepatitis B infection are eligible provided they are 
HbsAg negative and have an undetectable HBV DNA viral load; Subjects with a 
history of hepatitis C infection are eligible provided they have no evidence of HCV 
RNA using a quantitative polymerase chain reaction (qPCR) test at least 6 months 
after completing treatment for hepatitis C infection. 
14. Has received a live-virus vaccine within 30 days of treatment start. 
Note: Seasonal flu vaccines that do not contain live virus and messenger RNA 
(mRNA) COVID-19 vaccines are permitted. 

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15. Has a history of (non-infectious) pneumonitis / interstitial lung disease that 
required steroids or has current pneumonitis / interstitial lung disease. 
16. Has an active infection requiring systemic treatment or has a bleeding tumor. 
17. Existing stomach or duodenal ulcer, gastrointestinal disease affecting drug 
absorption (e.g. Celiac disease, Crohn’s disease, etc.) or previous bowel resection 
which is considered clinically significant or could interfere with absorption. 
18. Is unable or unwilling to take folic acid or vitamin B12 supplementation. 
19. Requires vitamin K antagonists. 
Note: Factor Xa antagonists are permitted if clinically required or required to 
maintain the patency of venous access. 
20. Treatment with any medication which is predominantly metabolized by CYP3A4 
and has a narrow therapeutic index. 
21. Known severe hypersensitivity (≥Grade 3) to bemcentinib, pemetrexed, 
carboplatin or pembrolizumab and/or any of the excipients. 
22. Has received radiation to the lung of >30 Gray within 6 months of study entry. 
23. Has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the clinical study, interfere with 
the subject’s participation for the full duration of the clinical study, or means it is 
not in the best interest of the subject to participate, in the opinion of the 
Investigator. 
24. Has a known psychiatric or substance abuse disorder that would interfere with 
cooperation with the requirements of the clinical study. 
5.3 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study 
but are not eligible for participation according to inclusion/exclusion criteria. The minimal 
information required to be collected includes informed consent date, demography, 
screen failure reason(s), eligibility criteria, and any SAE. A screen failure rate of 30% is 
expected. 
Any screen failure subject should be registered as such in the interactive response 
technology system (Rave RTSM) and in the eCRF. 
Individuals who do not meet the criteria for participation in this clinical study (screen 
failure) at the end of the 28-day screening period, may be rescreened after discussion 
with the Medical Monitor. If the subject has failed one of the inclusion criteria or fulfilled 
one of the exclusion criteria related to laboratory parameters, re-sampling is allowed 
only once per subject within a 28-day window from the point of screen failure. In case of 
technical issues (e.g. hemolyzed or lost samples), re-sampling is allowed for the affected 
parameters. Rescreened subjects should be assigned the same subject number as for 
the initial screening. 

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6 
TREATMENTS 
 
6.1 
Treatments Administered 
 
6.1.1 
Investigational Medicinal Product (Bemcentinib) 
The Investigator must document that instructions for bemcentinib administration are 
given to the subject verbally and in writing at the first dispensing visit (C1D1). 
Bemcentinib will be provided by Sponsor according to the details presented in Table 2. 
The administration of bemcentinib is described in Section 6.1.3. 
Table 2 Study Medication Provided by Sponsor 
 
Study Medication Name 
Bemcentinib (investigational medicinal product [IMP]) 
Dose Formulation 
Size 0, Swedish Orange, HPMC capsule 
Unit Dose Strengths 
50 mg, 75 mg or 100 mg 
Dosage Levels 
75 mg, 100 mg, 125 mg, or 150 mg 
Daily within 4 hours of consuming food 
Route of Administration 
Per oral 
Use 
Experimental 
Packaging and Labelling 
The capsules are supplied in multidose 50 mL HDPE bottles, 
each containing 22 capsules and closed with a child-resistant, 
tamper-evident screw cap 
Each container will be labelled as required per country 
requirement 
Storage 
Stored at or below 25°C/77°F 
Abbreviations: HMPC=hydroxypropyl methylcellulose; HDPE high density polyethylene 
 
6.1.2 
Investigational Medicinal Products (Europe)/Standard of Care (United 
States) (Pembrolizumab, Pemetrexed and Carboplatin) 
The products pembrolizumab and pemetrexed have market authorizations across US, 
EU, and UK corresponding to the use in the study. 
Pembrolizumab, pemetrexed and carboplatin will be classified as IMPs and supplied by 
the Sponsor in Europe and prescribed as SOC in the US through the clinical study. They 
will be administered according to Table 3 and further detailed in Section 6.1.3. 
Carboplatin has a market authorization across US, EU, and UK for ovarian cancer and 
SCLC, i.e., it is not specifically authorized for the combination treatment for 
non-squamous NSCLC specified in the protocol. However, pembrolizumab, in 
combination with pemetrexed and platinum chemotherapy, is indicated for the 1L 
treatment of metastatic non-squamous NSCLC in adults whose tumors have no EGFR or 
ALK positive mutations. The most frequently used platinum-agent in this target 
population is carboplatin. The combination of pembrolizumab plus platinum and 
pemetrexed is recommended in the international guidelines, (i.e. ESMO, ASCO, and 
NCCN) for the treatment of patients with previously untreated metastatic non-squamous 
NSCLC without sensitizing EGFR/ALK alterations, irrespective of PD-L1 expression. In the 
KEYNOTE-021 study, patients with advanced non-squamous NSCLC were treated with 
pemetrexed and carboplatin with or without pembrolizumab. Response (ORR and PFS) 
and OS were improved in the pembrolizumab combination versus chemotherapy, 

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regardless of PD-L1 status (Awad et al., 2021). These recommendations were confirmed 
based on data from the phase 3 KEYNOTE-189 study, where the patients treated with 
pembrolizumab, pemetrexed, and platinum-based chemotherapy compared with 
chemotherapy alone had significantly improved the survival outcomes (Gadgeel et al., 
2020; NCCN, 2022; Planchard et al., 2018; Planchard et al., 2020). Most of the patients 
included in these trials were treated with carboplatin, and only some of them were 
treated with cisplatin as the platinum-containing part of the combination. Furthermore, 
real world data from the SEER registry also found that in practice most patients 
undergoing treatment for stage IV NSCLC received carboplatin, while only 4.5% of 
patients received cisplatin. Carboplatin is used more commonly than cisplatin because it 
has less non-hematologic toxicity and is easier to administer in the outpatient setting, 
because it does not require vigorous hydration regimens (Zhu et al., 2013). Altogether, 
this supports the use of carboplatin in SOC across US, EU, and UK. 

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Table 3 Chemo-Immunotherapy 
 
Study Medication 
Name 
Pembrolizumab 
Pemetrexed 
Carboplatin 
Dose Formulation 
Concentrate for 
solution for infusion 
Powder or concentrate 
for solution for infusion 
Concentrate for 
solution for infusion 
Dosage Levels 
200 mg 
Administration on 
Day 1 of each 21-day 
cycle prior to 
chemotherapy 
500 mg/m2 BSA 
Administration on 
Day 1 of each 21-day 
cycle 
AUC5* 
Administration after 
completion of the 
pemetrexed infusion 
on Day 1 of each 
21-day cycle* 
Route of 
Administration 
IV infusion 
IV infusion 
IV infusion 
Use 
CIT 
CIT 
CIT 
Storage 
As per prescribing 
information 
As per prescribing 
information 
As per prescribing 
information 
Market 
authorization in US, 
EU, and UK 
Keytruda® 
Label: US, EU, UK 
In combination with 
pemetrexed and 
platinum 
chemotherapy, 
as first-line treatment 
of patients with 
metastatic non- 
squamous NSCLC, with 
no EGFR or ALK 
genomic tumor 
aberrations 
Pemetrexed 
Label: US 
In combination with 
pembrolizumab and 
platinum 
chemotherapy, for the 
initial treatment of 
patients with 
metastatic non- 
squamous non-small 
cell lung cancer 
(NSCLC), with no EGFR 
or ALK genomic tumor 
aberrations 
Carboplatin 
Label: US 
Ovarian cancer 
Label: EU, UK 
Ovarian cancer and 
SCLC 
Label: EU, UK 
In combination with 
cisplatin is indicated for 
the first-line treatment 
of patients with locally 
advanced or metastatic 
non-small cell lung 
cancer other than 
predominantly 
squamous cell histology 
* Carboplatin dose calculated using the Calvert equation: Carboplatin dose (mg)=AUC x (CrCl +25) or a 
maximum of 4 cycles. 
Abbreviations: BSA=body surface area; CIT=chemo-immunotherapy; CrCL=creatinine clearance; 
IV=intravenous 
 
6.1.3 
Treatment Regimen 
Subjects will receive bemcentinib once daily at one of 3 dose levels as per cohort (see 
below) in combination with CIT. 
Bemcentinib will be taken orally within 4 hours of consuming food. On visits when CIT 
and bemcentinib are given on the same day, bemcentinib must be given first and the 

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subject observed for 1 hour prior to administration of CIT during the first 
4 administrations. 
DLTs will be assessed on the first complete 21-day treatment cycle of the combination 
therapy. 
An independent DSMB will be responsible for reviewing the safety data from each cohort 
at the end of the DLT assessment period of that dose level and will provide 
recommendations to the Sponsor on the dose cohort management. 
Cohort 1: The first 3 subjects will be enrolled at 75 mg bemcentinib daily dosing. 
• 
If 0/3 subjects experience a DLT, initiate Cohort 2. 
• 
If 1/3 subjects experience a DLT, add 3 additional subjects at the same dose 
level. 
• 
If 1/6 subjects experience a DLT, initiate Cohort 2. 
• 
If 2/6 subjects experience a DLT, stop the clinical study. 
Cohort 2: 3 subjects will be enrolled at 100 mg bemcentinib daily dosing. 
• 
If 0/3 subjects experience a DLT, proceed to phase 2a expansion at this dose 
level and start Cohort 3 dose level in parallel. 
• 
If 1/3 subjects experience a DLT, add 3 additional subjects at the same dose 
level. 
• 
If 1/6 subjects experience a DLT, proceed to phase 2a expansion at this dose 
level and start Cohort 3 dose level in parallel. 
• 
If 2/6 subjects experience a DLT, de-escalate to Cohort 1 dose. 
Cohort 3: 3 subjects will be enrolled at 150 mg bemcentinib daily dosing. 
• 
If 0/3 DLTs, proceed to phase 2a expansion. 
• 
If 1/3 DLTs, add 3 additional subjects at this dose level. 
• 
If 1/6 DLTs, proceed to phase 2a expansion with this dose level. 
• 
If 2/6 DLTs, start alternative dosing regimen. 
Cohort 4: Alternative dose level if 2/6 experience DLTs in Cohort 3: 3 subjects will be 
enrolled at 125 mg bemcentinib daily dosing. 
• 
If 0/3 DLTs, proceed to phase 2a expansion with this dose level. 
• 
If 1/3 DLTs, add 3 additional subjects at this dose level. 
• 
If 1/6 DLTs, proceed to phase 2a expansion with this dose level. 
• 
If 2/6 DLTs, stop escalation. 
 
6.1.3.1 
Chemo-immunotherapy 
Chemo-immunotherapy should be administered on Day 1 of each 21-day treatment cycle 
after all procedures and assessments have been completed. The treatment can be 
administered +/- 3 days of the targeted Day 1 for each cycle, except Cycle 1 where 
treatment can only be administered + 3 days of the targeted Day 1. 
Subjects should receive CIT treatment in the following order: 
• 
Pembrolizumab infusion over 30 minutes followed by 

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• 
Pemetrexed infusion over 10 minutes followed by 
• 
Carboplatin infusion over 30-60 minutes. 
All subjects should receive antiemetic therapy according to local guidelines for the use of 
pembrolizumab plus pemetrexed and carboplatin. Higher or additional doses are 
permitted for antiemetic prophylaxis during Cycles 1 to 4. 
Pembrolizumab 
Pembrolizumab dose of 200 mg will be administered per institutional practice on the first 
day of each 21-day treatment cycle. 
Pembrolizumab may be administered up to 3 days before or after the scheduled Day 1 of 
each cycle due to administrative reasons (except Cycle 1, see above). 
Pembrolizumab will be administered as 30-minute IV infusion every 3 weeks (Q3W). 
Sites should make every effort to target infusion timing to be as close to 30-minutes as 
possible. However, given the variability of infusion pumps from site to site, a window 
of -5 minutes and +10 minutes is permitted (i.e., infusion time is 
30-minutes: -5 min/+10 min). 
 
Pemetrexed 
Pemetrexed dose of 500 mg/m2 BSA will be administered as an IV infusion per 
institutional practice on the first day of each 21-day treatment cycle. Pemetrexed will be 
administered as an IV infusion over 10 minutes Q3W until progression or unacceptable 
toxicity. All subjects should receive the appropriate supplementation of vitamin B12 and 
folic acid as well as corticosteroid prophylaxis as listed below: 
• 
At least 5 doses of folic acid must be taken during the 7 days preceding the first 
dose of pemetrexed, and folic acid dosing must continue during the full course of 
therapy and for 21 days after the last dose of pemetrexed. 
• 
Vitamin B12 1000 μg IM injection in the week preceding the first dose of 
pemetrexed and once every 9 weeks thereafter. Subsequent vitamin B12 
injections may be given the same day as pemetrexed administration. 
• 
Dexamethasone prophylaxis 4 mg, orally twice per day (or equivalent). Taken the 
day before, day of, and day after pemetrexed administration. 
Carboplatin 
Carboplatin AUC5 (=area under the concentration– time curve, 5 mg per milliliter per 
minute) will be administered per institutional practice after completion of the 
pemetrexed infusion on the first day of each 21-day treatment cycle for a maximum of 
4 cycles. 
Study subjects must receive adequate anti-emetic treatment and appropriate hydration 
prior to and/or after receiving carboplatin. 
Carboplatin AUC 5 mg/mL/min will be administered as an IV infusion over 30-60 minutes 
Q3W for 4 cycles immediately after pemetrexed as per local practice. 
6.2 
Preparation/Handling/Storage/Accountability 
Only subjects enrolled in the clinical study may use study medication and only delegated 
site staff may handle, dispense and/or administer study medication. 

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6.2.1 
Preparation of Study Medication 
 
6.2.1.1 
Bemcentinib 
Each site will be supplied with sufficient bemcentinib for the clinical study on an ongoing 
basis. Bemcentinib will be distributed to the sites according to screening numbers. 
Bemcentinib is provided in bottles containing a specified number of capsules per bottle 
to dispense to the clinical study subjects. The subjects will be asked to take the specified 
number of capsules for their prescribed dose within 4 hours of food intake. For rescue 
therapy, see Section 6.5. 
On visits when CIT and bemcentinib are given on the same day, bemcentinib must be 
given first and the subject observed for 1 hour prior to the start of CIT administration 
during the first 4 administrations. 
6.2.1.2 
Pembrolizumab, carboplatin, and pemetrexed 
Pembrolizumab, carboplatin, and pemetrexed will be prepared as per institutional 
practice. 
6.2.2 
Handling and Storage 
Acceptable temperature ranges and conditions for storage and handling of the IMPs 
(Europe [CIT and bemcentinib]/US [bemcentinib only]) are described in the pharmacy 
manual (Europe)/IMP manual (US). 
The Sponsor will provide the IMPs (Europe)/bemcentinib (US) for each subject for the 
duration of their participation in the clinical study. 
The Investigator, or designee will dispense bemcentinib on Day 1 of each treatment 
cycle. A sufficient quantity of bemcentinib will be dispensed to assure that the subject 
has sufficient supply to last at least until the next scheduled drug dispensing visit. The 
Investigator must ensure that no subject uses expired bemcentinib at any time. 
Subjects will be familiarized with bemcentinib administration prior to the first 
administration, and as needed, at the site. The Investigator must document that 
instructions for use are given to the subject verbally, and in writing. 
• 
The Investigator must confirm that appropriate temperature conditions have been 
maintained during transit for all IMPs (Europe)/bemcentinib (US) received, and 
that any discrepancies are immediately reported to the Sponsor and the IMPs 
(Europe)/bemcentinib (US) quarantined separately at recommended storage 
condition and resolved before release from quarantine and use. 
• 
IMPs (Europe)/bemcentinib (US) must be stored in a secure, controlled, and 
monitored (manual or automated) area in accordance with the labelled storage 
conditions with access limited to the Investigator and delegated site staff. 
• 
The Investigator must inform the Sponsor immediately if any IMP 
(Europe)/bemcentinib (US) has been stored outside of the specified conditions 
(exposed to light or outside recommended temperature). IMPs 
(Europe)/bemcentinib (US) must be quarantined separately at the recommended 
storage condition and must not be dispensed or administered to any subject 
before the storage excursion has been evaluated and approved for release from 
quarantine and further use by Sponsor. Additional details regarding handling of 
temperature deviations can be found in the pharmacy manual. 

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6.2.3 
Investigational Medicinal Products (Europe)/Bemcentinib (US) 
Accountability 
The Investigator is responsible for drug accountability and record maintenance 
(i.e. receipt, accountability and final dispensation records). The Investigator must ensure 
that a designated person receives the IMPs (Europe)/bemcentinib (US) deliveries from 
the Sponsor or designee and that all such deliveries are: 
• 
Recorded. 
• 
Handled and stored safely and properly. 
• 
Returned to Sponsor or designee, as required. 
The Investigator or designee must keep drug inventory and accountability logs of which 
a copy must be given to the Sponsor at the end of the clinical study. An accurate record 
of the date and amount of IMP (Europe)/bemcentinib (US) dispensed to and returned 
from each subject must be available for inspection at any time. The inventory logs will 
include details of IMPs (Europe)/bemcentinib (US) received and dispensed to the 
subject. All opened and unopened bottles of bemcentinib must be kept and returned to 
site. The clinical research associate (CRA) will perform reconciliation of delivery records 
and accountability logs for all IMPs (Europe)/bemcentinib (US). Discrepancies between 
the amount of IMP (Europe)/bemcentinib (US) received, dispensed, and returned will be 
verified. 
Subjects should be instructed to bring all their bemcentinib to Day 1 of each treatment 
cycle. Investigator or delegated staff must perform drug accountability with the subject 
on Day 1 of each treatment cycle. 
In case the Investigator, the site staff, or the CRA suspect that any IMP 
(Europe)/bemcentinib (US) is defective or potentially defective, the Sponsor should be 
contacted immediately, and a complaint raised. 
6.2.4 
Return and Destruction of Investigational Medicinal Products 
(Europe)/Bemcentinib (US) 
• 
Returned bemcentinib must be stored separately from non-allocated bemcentinib. 
• 
Destruction/return of IMPs (bemcentinib and CIT [Europe]/bemcentinib [US]) 
(used and unused) must be approved by the Sponsor. 
• 
At the conclusion of the clinical study (or by agreement with Sponsor during the 
clinical study if e.g. storage capacity at site is limited) the Investigator will 
return/destroy locally all used and unused IMPs (Europe)/bemcentinib (US) 
following authorization from the Sponsor. 
• 
Destruction/return of bemcentinib can be performed on an ongoing basis, 
following authorization from the Sponsor, and will be done according to local 
procedures after accountability is finalized by the site and reconciled by the CRA. 
• 
Destruction of used/expired CIT IMPs (Europe) can be performed without 
authorization from the Sponsor as per local procedures. Evidence of destruction 
and completed accountability will be reviewed by the CRA. 
• 
All returned, un-used, expired or damaged IMPs (bemcentinib and CIT 
[Europe]/bemcentinib [US]) must be stored separately from non-allocated IMPs 
(Europe)/bemcentinib (US). No temperature monitoring is required (for technical 
complaint, see Section 6.2.5). 

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• 
Non-allocated IMPs (bemcentinib and CIT [Europe]/bemcentinib [US]) including 
expired or damaged product must be accounted as unused, at the latest at 
closure of the site. 
6.2.5 
Reporting Product Complaints 
Pharmaceutical technical complaints associated with Sponsor-provided IMPs 
(Europe)/bemcentinib (US) must be reported to the Sponsor immediately. The same 
reporting timelines as for SAEs apply. 
6.3 
Treatment Compliance 
 
6.3.1 
Bemcentinib 
• 
The subject will be asked to bring all bottles, including the empty ones, with them 
to Day 1 of each treatment cycle to check compliance and for the Drug 
Accountability and Dose Log to be completed in the eCRF. 
6.3.2 
All Clinical Study Medications 
• 
Administration, missed doses, or failures in compliance will be recorded in the 
subject’s file and eCRF. The subject will be instructed as to the importance of 
taking their bemcentinib in accordance with instructions. 
• 
If it is discovered that an overdose has or may have been administered and the 
subject has experienced an adverse outcome as a consequence, the Investigator 
should complete the designated AE or SAE eCRF page. Expeditious handling and 
reporting is required. 
Throughout the clinical study, the Investigator will remind the subjects to follow the 
study procedures and requirements to encourage subject compliance. 
When subjects are dosed at the site, they will receive bemcentinib directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered at the site will be recorded in the source documents. 
When subjects self-administer bemcentinib at home, compliance with bemcentinib 
administration will be assessed and recorded in source documents at each visit where 
information is available. If any suspicion of non-compliance arises, apart from 
occasionally missed doses, the site must enter into a dialogue with the subject, 
re-emphasizing the importance of compliance and uncover barriers to compliance. This 
dialogue must be documented. Compliance will be assessed by cross checking the 
following sources and comparing these to the expected use (include at least 2 methods): 
• 
Drug accountability information; counting returned bemcentinib. 
• 
Questioning of subject. 
• 
Other. 
Treatment start and stop dates will be recorded in the eCRF. 
 
6.4 
Concomitant Therapy 
In general, no concomitant therapy should be started before consulting with the 
Investigator. 
Any medication or vaccine (including over the counter or prescription medicines, 
vitamins, and/or herbal supplements) other than bemcentinib and CIT that the subject is 

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receiving at the screening visit or receives during the clinical study must be recorded in 
the eCRF along with: 
• 
Generic name. 
• 
Indication. 
• 
Dates of administration including start and stop dates. 
• 
Additional information, such as dose and unit, frequency, start time, stop time 
and route of administration, should be recorded. 
Investigators may prescribe concomitant medications or treatments to provide adequate 
supportive care as deemed necessary, except for medications listed in Section 6.5. The 
Medical Monitor should be contacted if there are any questions regarding concomitant 
therapy. 
Changes in concomitant medication must be recorded at each visit. If changes occur 
during the clinical study period, documentation of drug dosage, frequency, route, and 
date may also be included on the eCRF. 
If a change is due to an AE, then this must be reported according to Section 10.3.3. 
 
6.4.1 
Premedication 
Anti-emetic premedication and additional supportive medication should be administered 
per local guidelines. 
All subjects should receive premedication with folic acid, vitamin B12, and corticosteroid 
administered according to local guidelines for pemetrexed use. 
6.5 
Prohibited Medication 
In general, medications or vaccinations specifically prohibited in the exclusion criteria 
are not allowed for the entire duration of the clinical study. Treatment with antacids, 
proton pump inhibitors, and histamine receptor 2 inhibitors can be initiated as rescue 
therapy after subjects have been receiving bemcentinib for one week, provided they are 
taken in the evening. 
If there is a clinical indication for any medication or vaccination specifically prohibited 
during the clinical study, discontinuation from the clinical study may be required. The 
Investigator should discuss any questions regarding this with the Medical Monitor. The 
final decision on any supportive therapy or vaccination remains with the Investigator 
and/or the subject’s primary physician. However, the decision to continue the subject on 
study medication requires the mutual agreement of the Investigator, the Sponsor, and 
the subject. 
For easy reference, a copy of medications that carry the risks of QT prolongation and 
must be avoided have been included in Appendix 6. A list of prohibited medications is 
provided in Appendix 7. 
6.6 
Effects on the Ability to Drive and Use Machines 
Pemetrexed can cause fatigue and carboplatin can cause acute hypersensitivity reactions 
with a drop in blood pressure in some subjects. Therefore, subjects must be cautioned 
against driving or the operation of machines if these effects occur. 

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6.7 
Treatment Dose Modification 
If appropriate, the Investigator may attribute each toxicity event to carboplatin, 
pemetrexed, pembrolizumab, bemcentinib alone, or to the combination and use a 
stepwise dose reduction according to Table 4, Table 5, Table 6, and Table 7. Dose 
modifications must be based on the maximum toxicity experienced during a treatment 
cycle. Toxicity needs to resolve to Grade ≤1 or baseline prior to resuming subsequent 
cycle. For individual subjects requiring a dose modification, treatment for each new cycle 
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 subject. 
Pembrolizumab dose reductions are not permitted. Pembrolizumab treatment may be 
interrupted or discontinued due to toxicity. If a subject 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). Reduction of one chemotherapy agent and not the other agent is appropriate if, 
in the opinion of the Investigator, the toxicity is clearly related to one of the treatments. 
If, in the opinion of the Investigator, the toxicity is related to the combination of 
chemotherapy agents, all drugs should be reduced according to recommended dose 
modifications. 
Chemotherapy may be interrupted for a maximum of 6 weeks; pembrolizumab may be 
interrupted for a maximum of 12 weeks. Bemcentinib may be interrupted for a 
maximum of 2 weeks (applicable only for phase 2a of the clinical study). 
The following dose modifications guidelines help guide modification of treatment doses of 
bemcentinib and CIT depending on the nature of toxicity reported. 

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Table 7 Dose Modifications for Chemo-Immunotherapy 
 
Dose Level 0 
Dose Level -1 
Dose Level -2 
Dose Level -3 
Pembrolizumab 
200 mg fixed 
dose. 
Dose reductions 
are not 
permitted 
Dose reductions 
are not 
permitted 
Dose reductions 
are not 
permitted 
Pemetrexed 
500 mg/m2 
375 mg/m2 
250 mg/m2 
Discontinue 
Carboplatin 
AUC5 
Maximum dose 
750 mg 
AUC3.75 
Maximum dose 
562.5 mg 
AUC2.5 
Maximum dose 
375 mg 
Discontinue 
Source: Gandhi et al., 2018 
 
AEs (both non-serious and serious) associated with pembrolizumab exposure may 
represent an immunologic etiology. These AEs may occur shortly after the first dose or 
several months after the last dose of treatment. Pembrolizumab must be withheld for 
drug-related toxicities and severe or life-threatening AEs as per Table 8 below. 
Table 8 Dose Modification Guidelines for Pembrolizumab Drug-Related AEs 
 
Toxicity 
Hold 
Treatment 
for Grade 
Timing for Restarting 
Treatment 
Treatment Discontinuation 
Diarrhea/colitis 
2-3 
Toxicity resolves to 
Grade 0-1 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent 
per day within 12 weeks 
4 
Permanently 
discontinue 
Permanently discontinue 
AST, ALT, or 
increased 
bilirubin 
2 
Toxicity resolves to 
Grade 0-1. 
Toxicity does not resolve within 
12 weeks of last dose 
3-4 
Permanently 
discontinue (see 
exception below)a 
Permanently discontinue 
Type 1 
diabetes 
mellitus (if 
new onset) or 
hyperglycemia 
Type 1 
diabetes 
mellitus or 
3-4 
Hold pembrolizumab 
for new onset Type 1 
diabetes mellitus or 
Grade 3-4 
hyperglycemia 
associated with 
evidence of beta cell 
failure 
Resume pembrolizumab when 
subjects are clinically and 
metabolically stable 
Hypophysitis 
2-4 
Toxicity resolves to 
Grade 0-1. Therapy 
with pembrolizumab can 
be continued while 
endocrine replacement 
therapy is instituted 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent per 
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Toxicity 
Hold 
Treatment 
for Grade 
Timing for Restarting 
Treatment 
Treatment Discontinuation 
Hyperthyroidism 
3 
Toxicity resolves to 
Grade 0-1 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent per 
day within 12 weeks 
4 
Permanently discontinue 
Permanently discontinue 
Hypothyroidism 
Therapy with 
pembrolizumab can be 
continued while thyroid 
replacement therapy is 
instituted 
Therapy with pembrolizumab can be 
continued while thyroid replacement 
therapy is instituted 
Infusion 
Reaction 
2b 
Toxicity resolves to 
Grade 0-1 
Permanently discontinue if toxicity 
develops despite adequate 
premedication 
3-4 
Permanently discontinue 
Permanently discontinue 
Pneumonitis 
2 
Toxicity resolves to 
Grade 0-1 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent per 
day within 12 weeks 
3-4 
Permanently discontinue 
Permanently discontinue 
Renal failure 
or nephritis 
2 
Toxicity resolves to 
Grade 0-1 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent per 
day within 12 weeks 
3-4 
Permanently discontinue 
Permanently discontinue 
All other 
drug- related 
toxicityc 
3 or Severe 
Toxicity resolves to 
Grade 0-1 
Toxicity does not resolve within 
12 weeks of last dose or inability to 
reduce corticosteroid to 10 mg or 
less of prednisone or equivalent per 
day within 12 weeks 
4 
Permanently discontinue 
Permanently discontinue 
Note: Permanently discontinue for any severe or Grade 3 (Grade 2 for pneumonitis) 
pembrolizumab-related AE that recurs or any life- threatening event. 
a. For subjects with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT increases by 
≥50% relative to baseline and lasts for at least 1 week then subjects should be discontinued. 
b. If symptoms resolve within one hour of stopping drug infusion, the infusion may be restarted at 50% of the 
original infusion rate (e.g., from 100 mL/hr to 50 mL/hr). Otherwise, dosing will be held until symptoms 
resolve and the subject should be premedicated for the next scheduled dose. 
c Subjects with intolerable or persistent Grade 2 drug-related AE may hold pembrolizumab at physician 
discretion. Permanently discontinue pembrolizumab for persistent Grade 2 adverse reactions for which 
treatment with pembrolizumab has been held, that do not recover to Grade 0-1 within 12 weeks of the last 
dose. 
Source: Gandhi et al., 2018 

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Recommended dose modifications for key pemetrexed and carboplatin toxicities are 
outlined in Table 9 and Table 10. These serve as a guide and do not replace Investigator 
judgment and applicable local label recommendations if more stringent. 
Table 9 Recommended Dose Modifications for Key Pemetrexed and Carboplatin 
Hematological Toxicity 
 
Pemetrexed 
Carboplatin 
Platelets 
ANC 
Dose level (DL) from Table 7 
≥50 AND 
≥0.5 
DL 0 
DL 0 
≥50 AND 
<0.5 
DL -1 
DL -1 
<50 without bleeding AND 
ANY 
DL -1 
DL -1 
<50 with Grade ≥2 bleeding 
AND 
ANY 
DL -2 
DL -2 
ANY AND 
<1.0 + fever 
≥38.5°C 
(101°F) 
DL -1 
DL -1 
Source: Gandhi et al., 2018 
Table 10 Recommended Dose Modifications for Pemetrexed and Carboplatin 
Non-Hematological Toxicity 
 
Pemetrexed 
Carboplatin 
Event 
CTC Grade 
Dose level (DL) from Table 7 
Nausea or vomiting 
Grade 3 or 4 
DL 0 
DL 0 
Diarrhea* 
Grade 3 or 4 
DL -1 
DL 0 
Mucositis 
Grade 3 or 4 
DL -2 
DL 0 
Neurotoxicity 
Grade 2 
DL 0 
DL 0 
Grade 3 or 4 
DL -1 
DL -1 
Transaminase elevation 
Grade 3 
DL -1 
DL -1 
Grade 4 
Discontinue 
Discontinue 
Other non-hematological 
toxicity 
Grade 3 or 4 
DL -1 
DL -1 
*requires hospitalization 
Source: Gandhi et al., 2018 
 
Management of Creatinine Clearance with Pemetrexed and Carboplatin 
Creatinine Clearance (CrCl) will be calculated on the original weight-based Cockcroft 
Gault formula (CrCl must be ≥45 mL/min prior to the administration of chemotherapy). 
Pemetrexed and/or carboplatin may be delayed for up to 42 days to allow the subject 
time to recover from the toxicity. If a subject’s CrCl value has not returned to 
≥45 mL/min within 42 days after the previous dose, carboplatin and/or pemetrexed 
must be discontinued. 
6.8 
Treatment After the End of the Clinical Study 
Subjects who are ongoing and continuing to derive clinical benefit from bemcentinib 
after 2 years will be offered access to bemcentinib via an alternative access 
program/study until disease progression (not applicable in France). 

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7 
TEMPORARY STUDY HALT/DISCONTINUATION OF STUDY MEDICATION 
AND SUBJECT WITHDRAWAL 
7.1 
Discontinuation of Study Medication 
Treatment of a subject may be discontinued at any time during the clinical study at the 
discretion of the Investigator and Sponsor for safety, compliance, or administrative 
reasons. 
A subject must be discontinued from study medication if: 
• 
Any safety concerns or AEs that in the opinion of the Investigator might place the 
subject at unacceptable risk, including any deterioration of a subject’s health 
state. 
• 
Pregnancy or intention to become pregnant. 
• 
Simultaneous use of an approved or non-approved IMP in another clinical study. 
• 
Confirmed disease progression. 
• 
The subject withdraws consent. 
• 
The subject is lost to follow up. 
 
Subjects can be discontinued from study medication if: 
If a subject prematurely discontinues study medication, the primary reason must be 
specified in the eCRF. If the subject continues in the clinical study without one or more 
of the study medications, the intent should be to follow the subject to the extent 
possible according to the planned visit schedule and assessments with the purpose of 
following the safety and efficacy of the subjects. Reason for visits not having been 
performed must be documented. 
The primary reason for discontinuation of study medication must be specified in the 
end-of-treatment-form in the eCRF. Final drug accountability must be performed. 
The following options are available: 
• 
AE (a reason must be provided). 
• 
Death. 
• 
Lost to follow up. 
• 
Lack of efficacy (defined as confirmed disease progression). 
• 
Withdrawal of consent by subject. 
• 
Pregnancy. 
• 
Other (a reason must be provided). 
Subjects who discontinue bemcentinib (for reasons other than disease progression) may 
continue CIT treatment, if this is considered in the best interest of the subject, as 
determined by the Investigator. 
Following permanent discontinuation of bemcentinib, the subject will attend an EoT visit, 
and will then be followed for safety evaluation during 30 days counting from the 
bemcentinib treatment discontinuation date, i.e., the safety follow-up phase, Figure 2. If 
the subject discontinued for any reason other than disease progression, the subject will 
remain on study but off bemcentinib and be followed for PFS, Figure 3. The subject must 

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continue to follow the schedule of assessments for CIT as applicable. All subsequent 
therapies must be recorded in the eCRF. 
Safety data will no longer be collected beyond the 30-day safety follow-up period after 
the last dose of bemcentinib. 
Efficacy data collection must continue as planned for as long as the subject remains on 
CIT treatment (for a maximum of 2 years) or until discontinuation, withdrawal of 
consent, lost to follow up or death has occurred. 
7.2 
Subject Withdrawal from the Clinical Study 
A subject may withdraw from the clinical study at any time at his/her own request 
(withdrawal of consent). The subject’s request to withdraw from the clinical study must 
always be respected. 
If a subject withdraws consent, the Investigator must ask the subject if he/she is willing, 
as soon as possible, to have an assessment performed according to the EoT visit. See 
the Flowchart for data to be collected. 
A subject must be withdrawn if any of the following applies: 
• 
Withdrawal of informed consent. 
• 
Safety concerns or AEs that in the opinion of the Investigator might place the 
subject at unacceptable risk for further participation in this clinical study or would 
likely make the subject unable to carry out the full clinical study. 
• 
Sponsor closure of the clinical study. 
• 
Pregnancy or intention to become pregnant. 
All efforts should be made for subjects to attend the EoT visit where all general, safety, 
and laboratory assessments should be performed as detailed in the Flowchart. 
Final drug accountability must be performed even if the subject is not able to come to 
the site. 
If the subject withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a subject withdraws from the clinical study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the site study 
records. 
Although a subject is not obliged to give his/her reasons for withdrawing, the 
Investigator should make a reasonable effort to ascertain the reasons, while fully 
respecting the subject’s rights. Where the reasons are obtained, the primary reason for 
withdrawal must be specified in the End of Study form in the eCRF. 
7.2.1 
Replacement of subjects 
In phase 1b of the clinical study, subjects who are not DLT evaluable will be replaced. 
To be DLT-evaluable, the subject must have received at least 80% of the bemcentinib 
dose (at least 17 of 21 days, with no more than 2 consecutive days of dosing missed) 
and completed evaluation for DLT in Cycle 1 or received a partial dose of bemcentinib 
and developed DLT during Cycle 1. 

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In phase 2a, subjects will not be replaced, unless they are not efficacy-evaluable 
(defined as subjects who discontinue study medication or withdraw from the study 
before a post-baseline disease assessment has been completed) to ensure at least 
20 efficacy-evaluable subjects are available at each dose level studied in phase 2a. 
7.2.2 
Lost to Follow-up 
A subject will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the site. 
The following actions must be taken if a subject fails to return to the site for a required 
study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as 
soon as possible and remind the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to and/or 
should continue in the clinical study. 
• 
Before a subject is deemed “lost to follow-up”, the Investigator must make every 
effort to regain contact with the subject (where possible, at least 3 telephone 
calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods). These contact attempts should be 
documented in the subject’s source document. 
• 
Should the subject continue to be unreachable, he/she will be considered `lost to 
follow-up’. 
 
7.3 
Clinical Study or Site Termination 
If the Sponsor or their representatives, Investigator, or Competent Authority officials 
discover conditions during the clinical study that indicate that the clinical study or site 
involvement should be terminated, this action may be taken after appropriate 
consultation with the Sponsor and the Investigator. Conditions that may warrant 
termination of the clinical study or involvement of a site include, but are not limited to: 
The discovery of an unexpected, serious, or unacceptable risk to subjects enrolled in the 
clinical study. 
The decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of bemcentinib. 
Failure of the Investigator to comply with pertinent clinical trial regulations. 
Submission of knowingly false information from the research facility to the Sponsor, 
CRA, or Competent Authority. 
Insufficient adherence to protocol requirements. 
Clinical study termination and follow-up will be performed in accordance with applicable 
local regulations. 

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8 
STUDY ASSESSMENTS AND PROCEDURES 
The following sections describe the assessments and procedures, while their timing is 
summarized in the Flowchart, Table 11. The assessment schedule is the same for phase 
1b and 2a. 
• 
Informed consent must be obtained before any study-related activity, using the 
current version of the subject information sheet informed consent form (ICF), see 
Section 10.1.4. Re-consenting of subjects is required to ensure the subject is 
consented to the latest version of the ICF. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all inclusion criteria and none of the exclusion criteria and the data 
must be supported in the subjects’ source documentation. 
• 
The Investigator will maintain a screening log to record details of all subjects 
screened and to confirm eligibility or record reason for screen failure, as applicable. 
• 
Re-screening is allowed once per subject. 
• 
At Screening, subjects will be provided with a card stating that they are participating 
in a clinical study and provided with contact details of relevant site staff that can be 
contacted in case of emergency. 
• 
Adherence to the study design requirements, including those specified in the 
Flowchart, is essential and required for study conduct. 
• 
Please refer to Section 6.3 for treatment compliance. 
• 
Review of ECG, laboratory reports etc. must be documented either on the documents 
or in the subject’s source documents. 
• 
Repeat samples may be taken for technical issues and unscheduled samples or 
assessments may be taken for safety reasons. Please refer to Appendix 2 for further 
details on laboratory samples. 
• 
On visit days, assessments should be performed prior to dosing unless specified 
otherwise. 
• 
Additional assessments may be carried out at any point in the clinical study where 
clinically indicated. 
 
Visit Windows 
A tolerance window of ± 3 days is permitted. Other tolerance windows for specific 
assessments are described in the footnotes of Table 11. 

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Table 11 
Flowchart – Assessment and Visit Schedule 
 
Visit Name 
Screening 
Treatment (21-day cycles) 
EoT19 
Safety 
follow- 
up20 
PFS 
follow- 
up21 
Survival follow- 
up22 
Treatment Cycle 
Screening 
1 
2 
3 
4 
5 
6 
>7 
Cycle day 
-28 to -1 
1 
2 
8 
15 
1 
1 
1 
1 
1 
1 
Informed consent 
X 
Informed consent for 
biomarkers 
X 
Inclusion/exclusion criteria 
X 
Demographics1 
X 
Medical/surgical history 
X 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
NSCLC diagnosis2 
X 
Prior anticancer 
treatments 
X 
Vital signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Echocardiogram or MUGA 
X 
12-Lead ECG in triplicate5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(X)5 

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Visit Name 
Screening 
Treatment (21-day cycles) 
EoT19 
Safety 
follow- 
up20 
PFS 
follow- 
up21 
Survival follow- 
up22 
Treatment Cycle 
Screening 
1 
2 
3 
4 
5 
6 
>7 
Cycle day 
-28 to -1 
1 
2 
8 
15 
1 
1 
1 
1 
1 
1 
Hematology6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical chemistry6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/INR and aPTT6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis7 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bemcentinib9 
X ------------------------------------------------ X 
Pembrolizumab10 
X 
X 
X 
X 
X 
X 
X 
(X) 
Pemetrexed11 
X 
X 
X 
X 
X 
X 
X 
(X) 
Carboplatin12 
X 
X 
X 
X 
(X) 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor imaging13 
X 
X 
X 
X 
X 
X 
Subsequent antineoplastic 
therapy details14 
X 
X 
(X) 
Blood sample for genomic 
DNA 
X 
Blood sample for serum 
biomarkers 
X 
X 
X 
X15 
PK16 
X 
X 
X 
X 

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Visit Name 
Screening 
Treatment (21-day cycles) 
EoT19 
Safety 
follow- 
up20 
PFS 
follow- 
up21 
Survival follow- 
up22 
Treatment Cycle 
Screening 
1 
2 
3 
4 
5 
6 
>7 
Cycle day 
-28 to -1 
1 
2 
8 
15 
1 
1 
1 
1 
1 
1 
Tumor Tissue sample 17 
X 
Liquid biopsy18 
X 
X 
Survival 
X 
Footnotes: 
1. 
Demography - race, ethnicity, gender, and age (birth month and year) 
2. 
NSCLC diagnosis details including date of initial diagnosis, date of advanced/metastatic disease, histological diagnosis, clinical staging, details on any 
non-actionable mutations noted. 
3. 
Vital signs will include temperature, systolic BP, diastolic BP, heart rate and respiratory rate. On pembrolizumab dosing days, vital signs will be taken both 
pre-dose and at the end of infusion. 
4. 
Physical examination includes height at Screening only and weight at Screening and at the start of each cycle. After the screening assessment, the physical 
examination may be reduced to a symptom-directed assessment. 
5. 
For each ECG assessment, triplicate 12-lead ECGs must be taken less than 5 minutes apart, with the subject having rested for at least 10 minutes in the supine 
position prior to assessment. On Cycle 1 Day 1 (C1D1), ECGs should be taken prior to the bemcentinib dose and 6 hours post-dose. All other timepoints are 
pre-dose only, unless clinically indicated. If a subject has bemcentinib interrupted for 14 days for toxicity, an ECG will be conducted twice weekly for the 
following 2 weeks once a subject restarts daily dosing. If a subject permanently discontinues bemcentinib (but continues any of the CIT drugs), the last ECG 
will be performed at the next visit, or at the safety follow-up visit. ECGs are not required for EoT of CIT drugs if bemcentinib was discontinued earlier and a 
final ECG assessment was performed. 
6. 
Hematology, clinical chemistry and coagulation to be assessed prior to administration of study medications; a sample draw window of max. 3 days is allowed to 
ensure results are available prior to Day 1 dosing. 
7. 
Urinalysis should be performed at Screening, C1D1, Cycle 1 Day 15 (C1D15) and then every other cycle thereafter. 
8. 
For women of reproductive potential, a urine pregnancy test should be performed within 72 hours prior to first dose of study medication. A serum test can be 
considered if urine is not appropriate. Monthly pregnancy testing should be conducted as per local regulations, before Day 1 of each cycle. 
9. 
Bemcentinib will be taken orally OD within 4 hours of consuming food. On visits when pembrolizumab and bemcentinib are given on the same day, bemcentinib 
must be given first and the subject observed for 1 hour prior to administration of pembrolizumab during the first 4 treatment cycles. 
10. Pembrolizumab dose of 200 mg will be administered IV per institutional practice on the first day of each 21-day cycle (timing window ± 3 days). 
11. Pemetrexed 500 mg/m2 BSA will be administered as an IV infusion per institutional practice on the first day of each 21-day cycle. 
12. Carboplatin AUC5 will be administered IV per institutional practice after completion of the pemetrexed infusion on the first day of each 21-day cycle for a 
maximum of 4 cycles (note: subjects must receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving carboplatin). 

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13. The same imaging method (CT or MR scan) should be used throughout the clinical study (timing window ± 7 days). Disease assessments should use the 
RECIST 1.1. iRECIST is to be used only if a subject is clinically stable and a pseudo-progression is suspected. A tumor response or disease progression should 
be confirmed no less than 28 days after the initial finding. If treatment administration is misaligned with weeks (e.g. because of treatment delay), the tumor 
imaging schedule should be maintained by week number. 
14. Details of any anticancer therapies received after the last dose of bemcentinib will be collected. 
15. Blood sample for serum biomarkers should be collected only at end of bemcentinib treatment. 
16. The maximum PK sampling timepoints for the measurement of bemcentinib in blood will be C1D1 pre-dose and 2- and 6-hours post-dose; Cycle 1 Day 2 
(C1D2) pre-dose; Cycle 1 Day 8 (C1D8) pre-dose; and C1D15 pre-dose. Samples should be taken contemporaneously with the ECG assessments and be 
marked with actual times. In the event of unit closures or holidays (or pandemic restrictions) PK samples can be missed with the prior approval of the Sponsor. 
All sample times are approximate, but every effort must be made to take PK samples at the specified times. Please refer to Table 12 and the local laboratory 
manual for full details on PK sample collection, timepoints, processing, storage, and shipment. 
17. All subjects must have histological confirmation of the diagnosis. Fresh or diagnostic/archival tumor tissue must be available (or expected from another 
institution) at the time of enrollment. Suitable diagnostic/archival biopsy material may also be obtained at Screening. NB: The biopsies should not be 
performed solely for study purposes, but it is expected that subjects will have biopsies performed as a part of their SOC procedure at the time of diagnosis. In 
the absence of adequate diagnostic/archival tumor material, study-specific biopsies will be requested. If it is not feasible to obtain a fresh study-specific biopsy, 
discuss with the Sponsor prior to excluding the subject from the study. 
18. Blood for liquid biopsy will be collected at 2 timepoints i.e. Screening and End of bemcentinib Treatment. In phase 1b, the enrollment of the patients onto the 
clinical study will be independent of the STK11m status (all comers). Phase 2a part of the clinical study, will, however, enroll only those patients who have a 
STK11m at Screening that is detected in the liquid and/or solid tumor biopsies. 
19. End of Treatment visit to be conducted within 14 days of last dose of each of the 4 drugs. 
20. Safety follow-up visit to be conducted 30 days (± 3 days) from the last dose of bemcentinib. AEs and concomitant medications must be assessed to 30 days. 
21. PFS follow-up is only for subjects who have discontinued any treatment (but not all 4) without progression. 
22. The survival follow-up will be conducted virtually (via a phone call) approximately every 3 months. The survival follow-up phase will start once the subject has 
discontinued ALL 4 drugs and not before. 

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8.1 
Demographics and Other Baseline Characteristics 
 
8.1.1 
Demographics 
Demographic information to be collected includes race, ethnicity, gender, and age (birth 
month and year). 
8.1.2 
Medical History/Concomitant Illness 
Medical history information to be collected includes all ongoing conditions and 
relevant/significant medical history including all major hospitalizations and surgeries as 
well as prior anticancer treatment for any malignancy, as applicable. 
Medical history is a medical event that the subject experienced prior to the time point 
from which AEs are collected. 
A concomitant illness is any illness that is already present at the time point from which 
AEs are collected or found as a result of a screening procedure or other study procedures 
performed before exposure to study medication. 
Concurrent illnesses recorded at Screening (excluding the primary disease under 
evaluation), that worsen in severity or frequency from the time of signing the consent 
form, but before treatment is initiated need to be reported as an AE if the event causes 
the patient to be excluded from the trial or is a result of a protocol specific intervention. 
In case of an abnormal and clinically significant finding fulfilling the definition of a 
concomitant illness or medical history, the Investigator must record the finding on the 
Medical History/Concomitant Illness form. 
8.1.3 
Physical Examinations 
A full physical examination will include assessment of the following categories: head, 
eyes, ears, nose, throat, heart, lungs, abdomen, skin, musculoskeletal, extremities, 
neurological, lymph nodes, and ‘other’. After the screening assessment, the physical 
examination may be reduced to a symptom-directed assessment. 
Body measurements (e.g. height and weight) will also be measured and recorded as 
specified in the Flowchart, see also Section 8.3.1. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.1.4 
ECOG Performance Score 
Details of the ECOG performance score categories are presented in Appendix 8. Subjects 
must be confirmed as ECOG performance score 0 or 1 at Screening to be eligible for 
study participation. 
8.1.5 
NSCLC Diagnosis 
Details of the NSCLC diagnosis including date of initial diagnosis, date of 
advanced/metastatic disease, histological diagnosis, clinical staging, and details of any 
non-actionable mutations will be recorded. 
8.1.6 
Tumor Tissue Sample 
All subjects must have tumor tissue available (or expected from another institution) at 
the time of enrollment. It is expected that subjects will have suitable biopsies performed 

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as part of their SOC, but in the absence or insufficiency of such material, study-specific 
biopsies will be requested. However, if the archival sample is not available or if it 
contains minimal tumor tissue and it is not feasible to collect a fresh biopsy, it should be 
discussed with the Sponsor prior to excluding subjects from the clinical study. 
8.1.7 
Liquid Biopsy NGS 
NGS analysis of a liquid biopsies (i.e., blood sample) will be performed to evaluate if the 
subject is harboring a mutation in the STK11 gene. 
For phase 1b, analysis may be carried out retrospectively as subjects will be included in 
the study independently of their mutational status in the STK11 gene. 
For phase 2a, prospective NGS will be carried out during Screening to identify subjects 
who harbor mutations in STK11 gene as only patients harboring a STK11 mutation will 
be enrolled to phase 2a. However, if during Screening for phase 2a, the STK11 gene is 
already known to harbor mutations, the subject will be enrolled to the study and NGS 
analysis maybe carried out retrospectively. 
Liquid biopsy samples will also be collected at the end of bemcentinib treatment for all 
subjects. 
8.2 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in Table 11. 
 
8.2.1 
Tumor Imaging 
Radiological assessment will be performed as per Table 11 with the first assessment 
performed at 42 days. 
Efficacy endpoints in this study, including ORR, DCR, DOR, PFS will all be based on 
tumor assessment scan evaluation as per RECIST 1.1 (Eisenhauer et al., 2009). 
Immune Response Evaluation in Solid Tumors (iRECIST) (optional) is to be used only 
when progression on RECIST 1.1 has been noted, the subject is clinically stable, and 
pseudo-progression is suspected (Seymour et al., 2017). 
RECIST assessments will be performed using contrast-enhanced computerized 
tomography or magnetic resonance imaging (MRI) assessments of chest, abdomen, and 
pelvis. Additionally, x-ray and bone scans may be used if required. Additional anatomy 
should be imaged as appropriate, based on signs and symptoms of individual subjects at 
baseline and follow-up. 
Baseline assessments should be performed during the 28-day screening period, and 
ideally should be performed as close as possible to the start of the study treatment. The 
screening imaging assessments must confirm the subject has measurable disease per 
RECIST 1.1 (see Section 5.1, Inclusion Criteria). 
All participants will be evaluated with radiographic imaging to assess their response to 
treatment. Imaging will be performed at 6 weeks (± 7 days) and 12 weeks (± 7 days) 
and then every 9 weeks (63 days ± 7 days) for the first 48 weeks in the treatment 
period. Imaging will be performed every 12 weeks (84 days ± 7 days) subsequently. 
For each subject, the same imaging modality used at Screening (CT or MR scan) must be 
used serially throughout the duration of study participation. All scan procedures will be 
performed according to standard local scan protocols to ensure consistency across study 
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All radiological and non-radiological (e.g. MRI) scans will be reviewed by the local site 
Investigator and, if possible, stored electronically at site. 
A maximum of 5 target lesions, maximum of 2 per organ, must be selected at baseline. 
All target lesions should be measurable. Target lesions should be selected on the basis of 
their size (longest diameter for non-nodal lesions or short axis for nodal lesions), and in 
addition, target lesions should lend themselves to reproducible repeated measurements. 
All remaining lesions present at baseline are considered non-target, irrespective of 
whether they are measurable or not. 
A tumor response or disease progression should be confirmed no less than 28 days after 
the initial finding. If treatment administration is misaligned with weeks (e.g. because of 
treatment delay), the tumor imaging schedule should be maintained by week number 
from baseline. 
8.3 
Safety Assessments 
Planned time points for all safety assessments are provided in Table 11. Safety includes 
treatment emergent AE/treatment emergent SAE – their frequency, duration, and 
severity; lab parameters, vital signs, and ECG changes based on CTCAE v5.0 and will be 
assessed by the following parameters: 
• 
Vital signs. 
• 
ECG. 
• 
Clinical laboratory tests (hematology, biochemistry, coagulation, pregnancy test, 
and urinalysis). 
• 
AEs and SAEs. 
• 
Immune mediated AEs. 
 
8.3.1 
Body Weight and Height 
Body weight (kg with 1 decimal accuracy) will be measured at all visits. Height (cm) will 
be measured at Screening only. 
Weight will be measured on a calibrated scale. Subjects should wear light clothing and 
no shoes. Stoma bags should be emptied prior to the measurement. 
8.3.2 
Vital Signs 
The following vital signs will be collected: body temperature (ºC) (measured according to 
the site’s usual procedure), pulse rate (beats/min), and seated diastolic and systolic 
blood pressure (mm Hg). During the treatment period visits, vital signs will be collected 
prior to administration of study treatment. 
On pembrolizumab dosing days, vital signs will be taken both pre-dose and at the end of 
the infusion. 
Blood pressure and pulse rate measurements should be preceded by at least 5 minutes 
of rest for the subject, in a quiet setting without distractions. Blood pressure and pulse 
rate measurements will be performed with a completely automated device. Manual 
techniques must be used only if an automated device is not available. 

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8.3.3 
Electrocardiogram 
• 
For each ECG assessment, triplicate 12-lead ECGs must be taken less than 5 minutes 
apart, with the patient having rested for at least 10 minutes in the supine position 
prior to the assessment. 
• 
ECGs will be recorded at 25 mm/sec. All efforts should be made to ensure that an 
identical ECG machine is used to collect traces for individual subjects throughout the 
duration of the clinical study participation. The Investigator or designated physician 
will review the ECG results. 
• 
If any clinically significant findings are observed on the ECG, the Investigator will 
record it as part of the medical history prior to C1D1, and as an AE after C1D1, if the 
finding represents a change from baseline. Clinically significant findings identified 
prior to C1D1 must be checked against the study exclusion criteria, see Section 5.2. 
• 
On C1D1, ECGs should be taken prior to the bemcentinib dose and 6 hours post- 
dose. All other timepoints are pre-dose only, unless clinically indicated. Note that the 
average value of the 3 assessments performed at each time point should be applied. 
Subjects may be excluded based on the initial triplicate assessment at Screening. 
• 
Subjects who discontinue bemcentinib but continue with CIT will stop undergoing 
regular ECGs. 
• 
If a subject has bemcentinib interrupted for 14 days for toxicity, an ECG will be 
conducted twice weekly for the following 2 weeks when the subject restarts daily 
dosing. This is to ensure cardiac safety monitoring while bemcentinib returns to 
steady state. 
• 
If a subject permanently discontinues bemcentinib (but continues CIT), the last ECG 
will be performed at the next visit. 
• 
12-lead ECG will be obtained as outlined in Table 11, using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QTcF, and RR 
intervals. 
8.3.4 
Echocardiography or MUGA 
An echocardiography or MUGA assessment will be performed at Screening. Clinically 
significant findings identified prior to start of dosing must be checked against the study 
exclusion criteria. 
8.3.5 
Clinical Safety Laboratory Assessments 
All protocol-required laboratory assessments, as defined in Appendix 2 must be 
conducted in accordance with the laboratory manual and Table 11. 
Safety laboratory tests include hematology, biochemistry, urinalysis, and coagulation 
parameters assessed are listed in Appendix 2. 
All samples should be taken prior to dosing, if dosing occurs on the same day as the 
study visit. The date and time of collection will be recorded in the source data and in the 
eCRF. 
All testing will be performed at each site’s local laboratory. 
Copies of laboratory accreditation certificates and reference ranges will be obtained from 
each study site prior to the analysis of their first subject sample. 

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If any clinically significant findings are identified from the safety laboratory assessments 
at Screening, the Investigator will record it as part of the medical history prior to C1D1 
and as an AE post-dose, where the finding represents a change from baseline or 
thereafter. Findings identified prior to C1D1 must be checked against the study inclusion 
and exclusion criteria. 
8.3.6 
Dose Limiting Toxicities 
Dose Limiting Toxicities will be assessed over the first 21 days of treatment for each 
subject. If 2/6 subjects experience a DLT in the first 21 days of the first cycle, at any 
dose level, no further subjects will be enrolled at that dose and the rules for dose 
de-escalation described in Section 6.1.3 will be applied. 
The safety and tolerability of the quadruplet combination will be assessed by the DSMB 
by reviewing the safety data from the DLT assessment period, i.e. the first 21 days from 
C1D1 for each subject. 
The safety data will include the frequency and severity of occurrence of treatment- 
related AEs including AEs leading to treatment interruptions and discontinuation, dose 
reductions (during the first 21 days) and changes in safety parameters (vital signs, 
laboratory values, physical examinations, ECG) since baseline. 
Subjects will take oral bemcentinib capsules within 4 hours of consuming food, according 
to the following schedules: 
• 
Cohort 1: Bemcentinib 75 mg daily. 
• 
Cohort 2: Bemcentinib 100 mg daily. 
• 
Cohort 3: Bemcentinib 150 mg daily. 
• 
Alternative dose level: Cohort 4: Bemcentinib 125 mg daily dose. 
If Cohort 3 is tolerable, no further dose escalation will occur. If Cohort 3 is not tolerable, 
an alternative dose level, Cohort 4, at 125 mg will be implemented. 
Based on overall safety and tolerability, the DSMB will recommend the bemcentinib dose 
for the phase 2a expansion cohort. 
Dose Limiting Toxicities 
A DLT is defined as an AE or SAE that occurs during Cycle 1 and cannot be attributed to 
disease progression, intercurrent illness, or concomitant medications. 
The following toxicities occurring during Cycle 1 will be considered a DLT, only if 
assessed as related (possibly, probably, and definitely related) to bemcentinib: 
• 
Grade 4 non-hematologic toxicity (non-laboratory). 
• 
Grade 4 hematologic toxicity (except thrombocytopenia) lasting ≥7 days. 
• 
Thrombocytopenia: 
- 
Grade 4 thrombocytopenia of any duration. 
- 
Grade 3 thrombocytopenia associated with clinically significant 
bleeding. 
• 
Any non-hematologic AE ≥Grade 3 in severity should be considered a DLT, with 
the following exceptions: 
- 
Grade 3 fatigue lasting ≤3 days. 

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- 
Grade 3 diarrhea, nausea, or vomiting if persistent <7 days with 
optimum prophylactic medication per standard of care. 
• 
Any Grade 3 or Grade 4 non-hematologic laboratory value if: 
- 
Clinically significant medical intervention is required to treat the 
subject, or 
- 
The abnormality leads to hospitalization, or 
- 
The abnormality persists for >7 days. 
- 
The abnormality results in a Drug induced Liver Injury. 
- 
Grade 3 QTcF by CTCAE v5.0 on triplicate ECGs (mean QTc 
>= 501 ms; >60 ms change from baseline). 
- 
Exceptions: Clinically non-significant, treatable, or reversible 
laboratory abnormalities including liver function tests, uric acid, etc. 
Imaging will be performed at the investigator’s discretion to rule out 
pancreatitis for asymptomatic Grade 3 or Grade 4 amylase or lipase 
increase. 
• 
Febrile neutropenia (FN): 
- 
FN 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. 
• 
Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 
• 
Any treatment-related toxicity that causes the subject to discontinue treatment 
during Cycle 1. 
• 
Grade 5 toxicity (death). 
All toxicities will be graded using NCI CTCAE Version 5.0 based on the Investigator 
assessment. 
None of the above toxicities when assessed as related to CIT will be included in the DLT 
assessment. Although all AEs will be recorded, only AEs reported as definitely, probably, 
or possibly related to bemcentinib will contribute toward the DLT assessment. 
To be DLT evaluable, the subject must have received at least 80% of the bemcentinib 
dose (at least 17 of 21 days, with no more than 2 consecutive days of dosing missed) 
and completed evaluation for DLT in Cycle 1 or received a partial dose of bemcentinib 
and developed DLT during Cycle 1. 
In phase 1b of the clinical study, subjects who are not DLT-evaluable will be replaced. 
 
8.4 
Adverse Events and Serious Adverse Events 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or 
the subject’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to any of the study medications, to 
study procedures, or that caused the subject to discontinue study medication or 
withdraw from the study. See further guidance in Section 10.3.3. 

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8.4.1 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs, whether serious or non-serious, must be collected from the time a signed and 
dated informed consent form is obtained and until the End of Study visit is performed. 
Progression of the cancer under study or death attributed to disease progression should 
not be considered an AE unless the Investigator considers it to be drug related. 
All AEs that occur after the consent form is signed must be reported by the Investigator 
if they cause the subject to be excluded from the trial or are the result of a protocol- 
specified intervention, including but not limited to washout or discontinuation of usual 
therapy, diet, placebo treatment, or a procedure. 
The reporting timeframe for AEs meeting any serious criteria is in Section 10.3.4. The 
Investigator will make every attempt to follow all subjects with non-serious AEs for 
outcome. 
The reporting timeframe for a new pregnancy is described in Section 8.4.5. 
Subjects will be observed for any signs or symptoms and asked about their condition by 
open questioning, such as “How have you been feeling since you were last seen?” at 
each contact with the study site. Subjects will also be encouraged to spontaneously 
report AEs occurring at any other time during the study. 
All AEs, regardless of seriousness, severity, or presumed relationship to any study 
medication, must be recorded and evaluated by the Investigator. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common aetiologia. If 
no diagnosis can be made, the Investigator should record each sign and symptom as 
individual AEs. Investigators must record their opinion concerning the relationship of the 
AE to any of the study medications. All measures required for AE management must be 
recorded in the source document and reported according to Sponsor instructions. 
• 
All AEs will be reported in the eCRF (SAEs will be reported in the SAE form). 
• 
AE information should as a minimum include the following: 
o 
Date and time of onset 
o 
Date and time of Investigators first information about the AE 
o 
Seriousness 
o 
Severity 
o 
Causal relationship with study medication 
o 
Measures taken as a consequence of the AE 
o 
Interruption or discontinuation of study medication 
o 
Outcome or date of resolution and final outcome 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
All SAEs will be recorded and reported to Sponsor immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3. The Investigator 
will submit any updated SAE information to Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation (i.e. after the safety follow-up visit). However, if the Investigator learns of 
any SAE, including death, at any time after a subject has been discontinued from the 

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study, and the Investigator considers the event to be reasonably related to the study 
medication or study participation, the Investigator must promptly notify the Sponsor. 
8.4.2 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
Care should be taken not to introduce bias when detecting AEs and/or SAEs. Open- 
ended and non-leading verbal questioning of the subject is the preferred method to 
inquire about AE occurrences. 
8.4.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs will be followed up until resolution, 
stabilization, the event is otherwise explained, or the subject is lost to follow-up (as 
defined in Section 7.2.2). Like the initial AEs, follow-up information is reported in the 
eCRF; for SAEs, paper forms will be used. Follow-up questions regarding SAEs are 
queried directly by Sponsor to the Investigator. Further Information on follow-up 
procedures is provided in Appendix 3. 
Follow-up information must be reported according to the following: 
• 
SAEs: All SAEs must be followed until the outcome of the events is 
“recovered/resolved”, “recovered/resolved with sequelae”, or “fatal”, and until all 
queries have been resolved. Cases of chronic conditions, cancer, or AEs ongoing 
at time of death (where death is due to another AE) may be closed with the 
outcome “recovering/resolving” or “not recovered/not resolved”. Cases can be 
closed with the outcome of “recovering/resolving” when the subject has 
completed the follow-up period and is expected by the Investigator to recover. 
The SAE follow-up information should only include new (e.g. corrections or additional) 
information and must be reported within 24 hours of the Investigator’s first knowledge 
of the information. This is also the case for previous non-serious AEs which subsequently 
become SAEs. 
• 
Non-serious AEs: Non-serious AEs must be followed until the outcome of the 
event is “recovering/resolving”, “recovered/resolved”, or “recovered/resolved 
with sequelae” or until the end of the follow-up period stated in the protocol, 
whichever comes first, and until all queries related to these AEs have been 
resolved. Cases of chronic conditions, cancer, or AEs ongoing at time of death 
(where death is due to another AE) may be closed with the outcome of 
“recovering/resolving” or “not recovered/not resolved”. Cases can be closed with 
the outcome of “recovering/resolving” when subject has completed the follow-up 
period and is expected by the Investigator to recover. 
The Investigator must ensure that the worst severity and seriousness of an event is 
consistent throughout the trial, i.e. if the severity of an AE changes over time, it should 
be reported as a single AE with the worst severity recorded. A worsening of an 
unresolved AE must be reported as follow-up with re-assessment of severity and/or 
seriousness of the event. 
If an AE is resolved and re-occurs later, it should be reported as a new AE. 
Queries or follow-up requests must be responded within 14 calendar days from the date 
of receipt of the request, unless otherwise specified in the follow-up request. 

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8.4.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities regarding the safety of subjects and the study 
intervention 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 intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and Investigators. 
For all studies, except those utilizing medical devices, Investigator safety reports must 
be prepared for suspected unexpected serious adverse reactions (SUSAR) according to 
local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
An Investigator receiving an Investigator safety report describing a SAE or other specific 
safety information (e.g. summary or listing of SAEs) from the Sponsor will review and 
then file it and will notify the IRB/IEC, if appropriate, according to local requirements. 
8.4.5 
Pregnancy 
WOCBP will have a pregnancy test carried out at Screening. This test must be carried 
out within 3 days prior to C1D1. A pregnancy test may be a urine or blood test as per 
local guidelines. A positive or equivocal urine test must be confirmed by a blood test. 
Subjects confirmed as pregnant will be excluded from participation in the clinical study. 
WOCBP will continue to have a pregnancy test before Day 1 of each cycle or at least 
monthly. 
Female subjects who have a postmenopausal status, require documented confirmation of 
this by having their FSH levels assessed at Screening. Where postmenopausal status is 
not confirmed, subjects will be required to undergo pregnancy testing per protocol to 
confirm suitability to proceed to dosing as described above for WOCBP. 
Pregnancy during the study should be avoided and the subjects must be instructed 
regarding highly effective contraception as per local guidelines (see contraception 
guidance in Appendix 4). 
Details of all pregnancies in female subjects and female partners of male subjects who 
sign informed consent will be collected after C1D1 and through to the outcome of the 
pregnancy, or up to 30 days following discontinuation of bemcentinib or if a patient 
initiates a new anticancer therapy, whichever is earlier. 
If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4. A 
study-specific pregnancy form will be provided for pregnancy reporting. 
If a subject becomes pregnant during the study, the subject should be withdrawn from 
the clinical study (see Section 7.2). 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 

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8.5 
Treatment of Overdose 
 
Bemcentinib 
Bemcentinib overdose is defined as any dose exceeding 150 mg of bemcentinib daily. In 
the event of an overdose, the subject should be observed closely for signs of toxicity. 
Appropriate supportive treatment should be provided, if clinically indicated. 
 
Pembrolizumab 
For this clinical study, a pembrolizumab overdose is defined as ≥1000 mg (5 times the 
dose) of pembrolizumab. No specific information is available for the treatment of an 
overdose of pembrolizumab. In the event of an overdose, the subject should be 
observed closely for signs of toxicity. Appropriate supportive treatment should be 
provided, if clinically indicated. 
Pemetrexed 
Reported symptoms of overdose include neutropenia, anemia, thrombocytopenia, 
mucositis, sensory polyneuropathy and rash. Anticipated complications of overdose 
include bone marrow suppression as manifested by neutropenia, thrombocytopenia and 
anemia. In addition, infection with or without fever, diarrhea, and/or mucositis may be 
seen. In the event of suspected overdose, the subject should be monitored with regular 
blood counts and should receive supportive therapy as necessary. The use of calcium 
folinate/folinic acid in the management of pemetrexed overdose should be considered. 
Carboplatin 
There is no known antidote for carboplatin overdose. If necessary, however, the subject 
may need supportive treatment relating to myelosuppression, renal, hepatic and 
auditory function impairment. Reports of doses up to 1600 mg/m2 indicate subjects 
become extremely ill and develop diarrhea and alopecia. Use of higher than 
recommended doses of carboplatin has been associated with loss of vision. 
If the pharmacy discovers that an overdose has or may have been administered, they 
should contact the Investigator immediately. In the event of an overdose, the 
Investigator should: 
• 
Contact the Medical Monitor immediately. 
• 
Closely monitor the subject for any AE/SAE and laboratory abnormalities until 
study treatment can no longer be detected systemically (at least 5 days). 
• 
Obtain a plasma sample for PK analysis within 5 days from the date of the last 
dose of study medication (only applicable for bemcentinib) if requested by the 
Medical Monitor (determined on a case-by-case basis). 
• 
Document the quantity of the excess dose as well as the duration of the overdose 
in the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the subject. 
8.6 
Pharmacokinetics 
 
8.6.1 
Analysis Population 
Pharmacokinetic analysis will be determined from subjects who receive at least 1 dose of 
bemcentinib and have evaluable PK data available. 

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8.6.2 
Determination of Bemcentinib Concentration in Plasma 
• 
Blood samples of approximately 4.5 mL will be collected for measurement of 
plasma concentrations of bemcentinib as specified in the Flowchart. 
• 
A maximum of 11 samples may be collected at additional time points during the 
study, if warranted and agreed upon between the Investigator and the Sponsor. 
• 
Samples should be taken contemporaneously with the ECG assessments and be 
marked with actual times. In the event of site closures or holidays (or pandemic 
restrictions) PK samples can be missed with the prior approval of the Sponsor. All 
sample times are approximate, but every effort should be made to take PK 
samples at the specified times. 
• 
The following PK samples will be taken during the study (all phases), Table 12. 
Table 12 Bemcentinib PK Sampling Timepoints and Permitted Windows 
 
Study Day 
Time Point (hour) 
Permitted Time Window 
Cycle 1 Day 1 
Pre-dose 
within 1 hour prior to dosing 
2h 
+/- 15 mins (from C1D1 dose) 
6h 
+/- 45 mins (from C1D1 dose) 
Cycle 1 Day 2 
Pre-dose 
within 1 hour prior to dosing 
Cycle 1 Day 8 
Pre-dose 
within 1 hour prior to dosing 
Cycle 1 Day 15 
Pre-dose 
within 1 hour prior to dosing 
 
• 
Full details on pharmacokinetic (PK) sample collection, timepoints, processing, 
storage, and shipment are provided in the local laboratory manual. 
• 
The actual date and time of each sample will be recorded. 
• 
Samples will be used to evaluate the PK of bemcentinib. Each plasma sample will 
be divided into 2 aliquots. Samples collected for analyses of bemcentinib plasma 
concentration may also be used to evaluate safety or efficacy aspects related to 
concerns arising during or after the study. 
• 
Genetic analyses will not be performed on these plasma samples [unless consent 
for this was included in the informed consent]. Subject confidentiality will be 
maintained. 
• 
Plasma samples for determination of bemcentinib will be analyzed by a laboratory 
using a validated bioanalytical method. Details of the analytical method used will 
be described in a bioanalytical report. 
 
8.6.3 
Pharmacokinetic Analysis 
PK parameters listed in Table 13 (but not limited to) will be derived from relevant 
bemcentinib plasma concentration data generated in each part of the study, utilizing a 
PK model. Full details of the PK methodology will be written in the PK analysis plan. 

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Table 13 Plasma PK Parameters 
 
Cmax 
The observed maximum plasma concentration after single dose 
administration 
Tmax 
The time to reach Cmax 
AUC(0-t) 
The area under the curve within a dosing interval, calculated by the 
linear up-log down trapezoidal method. 
Lz 
The apparent terminal rate constant estimated from individual linear 
regression of the terminal part of the log concentration vs. time curve 
T1/2 
The apparent terminal half-life, calculated by 0.693/lz 
 
8.7 
Pharmacodynamics 
Pharmacodynamic parameters will not be evaluated in this clinical study. 
 
8.8 
Genomics 
Blood for isolating circulating tumor DNA (CtDNA-liquid biopsies) will be collected at 
two timepoints (Screening and End of Treatment) as shown in Table 11. Blood samples 
will be processed at a specialty laboratory for isolation of DNA and subjected to 
sequencing to identify mutations in STK11 gene along with other genes on a panel. 
Approximately 20 mL of blood will be collected at each timepoint for the liquid biopsies. 
Additionally, DNA and RNA will be isolated from the tumor tissue for sequencing. 
Tumor tissue will be obtained from diagnostic blocks (archival tumor blocks used for the 
diagnosis of the patient at the hospital). If the diagnostic/archival block is not available 
or does not have adequate tumor for sequencing, then fresh tumor biopsy will be 
required. 
An additional 5-6 mL K2 EDTA blood tube will be collected at Screening to obtain normal 
genomic DNA to be used as control. 
Details of sample collection, processing, storage and shipping are provided in the study 
specific laboratory flowchart. 
8.9 
Biomarkers 
Blood and tumor DNA will be sequenced to obtain data on gene mutations. In phase 1b 
part of the clinical study, blood and solid tumor biopsies from all subjects will be 
sequenced for mutations retrospectively. In part 2a of the clinical study, liquid biopsies 
at Screening will be used to identify subjects who have mutations in the STK11 gene 
before enrollment in the clinical study. Subjects harboring STK11 mutations, as reported 
by the hospital will also be enrolled on the clinical study, but the mutational status will 
be validated by the assessment of liquid and solid tumor biopsies. Solid tumor material 
will be subjected to a dual isolation of both DNA and RNA (for transcriptomics). 
Sections from tumor tissue (diagnostic block or fresh tumor biopsy) may be subjected to 
analysis of biomarkers such as AXL, PD-L1 and immune cell subtypes using 
immunohistochemistry (IHC) or other suitable techniques. A blood tube (4.5 mL) will be 
collected for isolation of serum for biobanking for analysis or validation of any 
biomarkers that may need assessment at a future timepoint. 
Blood and tumor material will be collected as shown in Table 11. 

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Details of sample collection, processing, storage, and shipping are provided in the 
study-specific laboratory flowchart. 
8.10 
Estimate of Total Blood Volume Collected 
Total blood volumes required during study participation will be provided in the Informed 
Consent Form provided to each patient. Blood samples will be drawn for hematology, 
clinical chemistry, coagulation, PK, liquid biopsies, biomarkers, and pregnancy test, if 
applicable, as per the Flowchart. The total volume of blood to be drawn is approximately 
50 mL at Screening, 100 mL during Cycle 1 and 50 mL during subsequent cycles. If 
additional blood samples are required, the amount of blood drawn may be more than 
this stated value, however the total volume of blood drawn per cycle will be less than the 
volume taken during a blood donation (approximately 400 mL). 
8.11 
Storage of Biological Samples 
• 
PK samples will be retained for as long as the quality of the material permits 
evaluation, but for no longer than 12 months after completion of the CSR. 
• 
Samples for hematology, clinical chemistry, coagulation, and urinalysis will not be 
stored. 
• 
All samples for biomarker and gene analysis will be stored by a central 
laboratory. When the study is completed, all samples collected for NGS (blood 
and tumor materials) will be stored in a regional ethical committee approved 
biobank for up to 5 years (unless longer is required to adequately address any 
queries from regulatory and governmental authorities) and may be used for 
analysis of biomarkers during this time. If the study subject authorizes the use of 
their biological samples for future research, their samples will be stored for up to 
25 years after study completion. Samples may however be retained for longer to 
adequately address any ongoing queries from regulatory and governmental 
authorities. 

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9 
STATISTICAL CONSIDERATIONS 
 
9.1 
Statistical Hypotheses 
No formal statistical hypotheses will be tested. 
 
9.2 
Sample Size Determination 
The basis for the sample size is based on non-statistical considerations. The analysis will 
be primarily descriptive in nature and the study is not statistically powered. 
9.3 
Analysis Sets 
The following populations are defined: 
Table 14 Analysis Sets 
 
Analysis set 
Description 
DLT-evaluable population 
set 
The DLT evaluable population set includes all enrolled subjects in 
phase 1b who received at least 80% of the bemcentinib dose 
during cycle 1 (at least 17 of 21 days, with no more than 
2 consecutive days of dosing missed) and completed evaluation 
for DLT in Cycle 1 or developed DLT during Cycle 1. 
Per-protocol analysis set 
(efficacy analysis set) 
The per-protocol analysis set comprises all subjects who received 
at least 1 dose of bemcentinib, without major protocol deviations 
with impact on efficacy and who have at least 1 post baseline 
efficacy assessment or have disease progression before the first 
post-baseline efficacy assessment (treatment failure). Criteria for 
exclusion from the per-protocol analysis set will be listed in the 
statistical analysis plan (SAP). Final decisions on exclusion from 
the per-protocol analysis set will be made prior to database lock. 
Safety analysis set 
(intention-to-treat set) 
All subjects who receive at least 1 dose of bemcentinib. Subjects 
are analyzed according to the treatment they actually received. 
Pharmacokinetic analysis 
set 
All subjects who received at least 1 dose of bemcentinib who have 
at least 1 evaluable PK assessment, without any major protocol 
deviations with relevant impact on PK analysis. 
 
The subjects or observations to be excluded, and the reasons for their exclusion must be 
documented before database lock. The subjects and observations excluded from analysis 
sets, and the reason for this, will be described in the CSR. 
9.4 
Statistical Analyses 
The statistical analysis plan (SAP) will include a more detailed description of the 
statistical analyses described in this section. This section is a summary of the planned 
statistical analyses of the most important endpoints including primary and secondary 
endpoints. 
An overview of the endpoints is provided in Table 1. 
 
9.4.1 
General Considerations 
Baseline for this clinical study is defined as the last pre-dose assessment. 

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9.4.2 
Primary Endpoints 
 
Phase 1b 
The primary endpoint of the phase 1b part of the study is the DLT during a 21-day DLT 
assessment period. 
The primary endpoint for phase 1b, will be analyzed on the DLT-evaluable population 
set, using only phase 1b data. The incidence of subjects with DLTs occurring during 
Cycle 1 will be summarized by cohort, and decisions for dose escalation will be 
performed by the rules stated in the study design and methodology section. 
Phase 2a 
The primary endpoint for phase 2a of the study is the ORR calculated from start of 
treatment (C1D1) to confirmation of response per RECIST 1.1 at 6 and 12 months. 
The primary endpoint of the phase 2a study will be analyzed on the per-protocol analysis 
set, using only phase 2a data. Analysis of ORR will occur in a Bayesian framework. The 
posterior distribution of both treatment groups will be obtained separately (and pooled if 
data are assumed to have equal performance), at each timepoint of interest; the 
posterior probability each dose level being greater than 33% will be estimated and the 
posterior probability of the high dose level being better than the low dose will also be 
estimated. 
The endpoint distribution is Bernoulli that means independent observations of the form: 
Yij~Binomial(1,pk) 
for treatment k=1,2 and for patient j=1,..,nk. 
In case of any missing data due to safety, death, or disease progression occurring after 
start of treatment, these patients will be considered as non-responders in the 
calculations above. Patients discontinuing due to lack of efficacy will also be considered 
as treatment failures. Early discontinuations for other reasons will not be imputed for the 
primary analysis, but imputation methods may be used for sensitivity analyses. 
The phase 1b part of the study may include subjects that would be eligible for the 
phase 2a at dose levels tested in phase 2a. In such case a sensitivity analysis may occur 
pooling data from the 2 parts of the study. 
9.4.3 
Secondary Endpoints 
 
9.4.3.1 
Confirmatory Secondary Endpoints 
Not applicable. 
 
9.4.3.2 
Supportive Secondary Endpoints 
All data on secondary endpoints will be listed. Quantitative data will be described by 
summary statistics and frequency tables will be provided for qualitative data. Time-to- 
event endpoints will be analyzed using Kaplan-Meier methodology. The 2 parts of the 
clinical study will be described and analyzed separately, should data from phase 1b part 
of the clinical study include subjects that would be eligible for the phase 2a at dose 
levels tested in phase 2a, then pooled analyses may be performed in an exploratory 
manner. 
For details on analyses of additional supportive secondary endpoints, please refer to the 
SAP. 

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9.4.4 
Exploratory Endpoints 
For details on analyses of exploratory endpoints, please refer to the SAP. 
 
9.4.5 
Other Safety Analyses 
All safety analyses will be made on the safety analysis set. The standard safety 
assessments (AEs, safety laboratory parameters, vital signs, etc.) will be reported 
descriptively, including any notable changes of clinical interest. For safety, each part of 
the study will be summarized separately, but pooled summaries for the selected doses 
may also be performed in case safety signals of such dose are identified. 
Vital signs 
All vital signs data will be listed by treatment, subject, and visit/time and if ranges are 
available abnormalities will be flagged. Summary statistics will be provided by study 
part, treatment and visit/time. 
ECG evaluations 
All ECG data will be listed by treatment, subject and visit/time, abnormalities will be 
flagged. Summary statistics will be provided by study part, treatment, and visit/time. 
As the ECG data are collected in triplicate, the intervals will be presented and 
summarized as the average of the replicate values at each timepoint instead of the 
individual values. 
Clinical laboratory evaluations 
All laboratory data will be listed by treatment, subject, and visit/time and if normal 
ranges are available abnormalities will be flagged. Summary statistics will be provided 
by study part, treatment, and visit/time. 
Adverse events 
All information obtained on AEs will be displayed by study part, treatment, and subject. 
The number and percentage of subjects with AEs will be tabulated by body system and 
preferred term with a breakdown by study part and treatment. A subject with multiple 
AEs within a body system is only counted once toward the total events within this body 
system. 
9.4.6 
Other Analyses 
For other analyses, please refer to the SAP. 
 
9.5 
Interim Analyses 
An interim analysis is planned when 20 subjects have completed 2 cycles of treatment in 
phase 2a and all 20 subjects have had their first response assessment performed (not 
earlier than Day 42). The Bayesian inferential analysis described above may be 
conducted to support decision making; based on this interim analysis, a dose level may 
be dropped due to futility, or the clinical study stopped, but no explicit efficacy or futility 
criteria are pre-specified, and evidence will be viewed in its totality due to the limited 
data expected to be available. 
Additional interim analyses may be conducted to support decision making concerning the 
current clinical study, the Sponsor’s clinical development program in general, or in case 
of safety concerns. 

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The SAP will describe the planned interim analyses in greater detail. 
 
9.6 
Independent Data Safety Monitoring Board 
The independent DSMB reviews and evaluates accumulated safety data from the clinical 
study at pre-defined intervals to assure subject safety and to evaluate benefit-risk 
balance during the conduct of the clinical study. The members of the DSMB will have 
expertise within the therapeutic area and other relevant medical areas as appropriate 
and the DSMB will provide recommendations to the Sponsor regarding study 
continuation, modification, or termination after each meeting. The responsibilities, 
procedures, and workflow of the DSMB are specified in the DSMB charter. 

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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
 
10.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and applicable ICH Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the Investigator and reviewed and approved by the IRB/IEC before the study is 
initiated 
• 
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study subjects 
The Investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.2 
Financial Disclosure 
Investigators and sub-Investigators will provide BGB with sufficient, accurate financial 
information as requested, to allow BGB to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests for the 
entire duration of the study and one year after completion of the study. 
For US sites: Verification under disclosures per Code of Federal Regulations (CFR) of 
Financial Conflict of Interest. 
10.1.3 
Liability and Insurance 
Appropriate insurance for this clinical study will be arranged by the Sponsor in 
accordance with the regulatory requirements of the countries involved. A copy of the 
country-specific insurance certificate will be held in the Trial Master File and in the 
Investigator Site File. 
The Sponsor will take out reasonable third-party liability insurance cover, in accordance 
with all legal requirements. The civil liability of the Investigator or designee and the 
hospital, practice, or institute in which they are employees and the liability of the 
Sponsor with respect to financial loss due to personal injury and other damage that may 
arise as a result of carrying out this clinical study are governed by the applicable law. 

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The Sponsor will arrange for liability insurance if study subjects should be injured due to 
the participation in the study provided that the Sponsor is legally liable for that. 
Excluded from the insurance cover are injuries to health and deteriorations of illnesses 
already in existence, which would have occurred or continued to exist even if the study 
subject had not taken part in the clinical study. 
The insurance cover is jeopardized if the study subject fails to report immediately to the 
Investigator or responsible physician any injury to health, which might have resulted 
from participation in the clinical study, or if the subject undergoes any other medical 
treatment without their consent before the clinical study has been completely finished 
insofar as the individual study subject is concerned. Any injury to health, which might 
have occurred as a result of participation in the clinical study, must be reported by the 
subject to the Investigator without delay. The Investigator is obliged to make such a 
report in any case. 
10.1.4 
Informed Consent Process 
• 
The Investigator or designee will explain the nature of the study to the subject 
and answer all questions regarding the study. This includes the use of an 
impartial witness where required, according to local requirements. 
• 
The Investigator must provide the subject ample time to come to a decision 
regarding study participation. 
• 
Subjects must be informed that their participation is voluntary. 
• 
Subjects must be informed about their privacy rights. 
• 
Subjects will be required to sign and date a statement of informed consent that 
meets the requirements of local regulations, ICH guidelines, Declaration of 
Helsinki and the IRB/IEC or site. 
• 
The medical record must include the date when the written informed consent 
was obtained and a statement that written informed consent was obtained before 
any study-related activity was performed. The authorized person obtaining the 
informed consent must also sign and date the informed consent form before any 
study-related activity is undertaken. 
• 
The responsibility of seeking informed consent must remain with the 
Investigator, however the Investigator may delegate the task to a medically 
qualified person, in accordance with local requirements. 
• 
Subjects must be re-consented to the most current version of the informed 
consent form during their participation in the study. 
• 
A copy of the informed consent form must be provided to the subject. 
 
Patient participation card 
A study participation card will be provided to each subject in the clinical study. The card 
will indicate that the subject is participating in a clinical study and include the name and 
contact details of the Sponsor and the Investigator/study site. The subject will be asked 
to retain this card for the entire duration of the study participation and show it to any 
other medical practitioners consulted during this time. Subjects will be advised to 
contact the Investigator/study site if there are any questions. 

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10.1.5 
Data Protection 
• 
Subjects will be assigned a unique identifier by the Sponsor. Any subject records 
or datasets that are transferred to the Sponsor will contain the identifier only; 
subject names or any information which would make the subject identifiable will 
not be transferred. 
• 
The subject 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 subject who will be required to give 
consent for their data to be used as described in the informed consent. 
• 
The subject 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. 
All data will be handled in accordance with the EU’s current Data Protection Law 
Enforcement Directive (European Parliament and Council of the European Union, 2016a), 
The General Data Protection Regulation (GDPR) (European Parliament and Council of the 
European Union, 2016b) and the local data protection regulations. 
For this study, the Sponsor and Investigational Site are the data controller of all data 
processed during the study and the clinical research organization (CRO) and other 
sub-contractors are data processors. 
In case the data security has been breached for any of the participants, the Sponsor 
must promptly but no later than 24 hours after becoming aware of the breach be 
notified. Prompt action to investigate the cause of the data breach must be made, and 
assistance to the Sponsor in complying with Articles 32 to 36 of the GDPR 
10.1.6 
Committees Structure 
An independent DSMB is established, and the roles and responsibilities defined in the 
DSMB charter. The DSMB will be responsible for reviewing the safety data from each 
cohort at the end of the DLT assessment period of that dose level, will provide 
recommendations to the Sponsor on the dose cohort management and will recommend 
the bemcentinib dose for the phase 2a expansion cohort. 
10.1.7 
Dissemination of Clinical Study Data 
Information regarding the study will be disclosed at clinicaltrials.gov and other publicly 
accessible sites (e.g. European Clinical Trials Database [EudraCT]). It will also be 
disclosed according to other applicable requirements, such as those of the International 
Committee of Medical Journal Editors (ICMJE), the Food and Drug Administration 
Amendment Act (FDAAA), European Commission Requirements (Directive 2001/20/EC 
and Regulation (EC) No 726/2004) and other relevant recommendations or regulations. 
If a subject requests to be included in the study via a BGB e-mail contact at these web 
sites, BGB disclose the Investigator’s contact details to the subject. As a result of 
increasing requirements for transparency, some countries require public disclosure of 
Investigator names and their affiliations. 
The primary completion date (PCD) is the last assessment of the primary endpoint and 
for this study it is the last subject first treatment + 25 months. The PCD determines the 
deadline for results disclosure at clinicaltrials.gov according to FDAAA. 

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10.1.8 
Data Quality Assurance 
 
10.1.8.1 Data recording 
BGB or designee is responsible for the data management of this study including quality 
checking of the data. 
The Investigator will be responsible for the recording of all data in the CRFs provided, as 
certified by the Investigator’s signature and date on the designated pages. All study data 
will be collected using an eCRF within a fully validated and CFR 21 Part 11-compliant 
electronic data capture system. All data will be entered into the eCRF by the site staff. 
These data will then be source data verified and reviewed by the CRA before data 
cleaning by Data Management is performed. All queries will be raised and resolved 
within the electronic data capture system. During entry, programmatic checking of the 
data will be performed and once saved into the database, more complex programmatic 
checks will also be performed. During the conduct of the study, all system users will 
have real-time access to the data. The level of access to the data and study privileges 
will be determined by their user role. 
After all queries have been resolved, the SAP approved and signed, and any 
summary/analysis populations approved, the database will be locked, and the data 
released for summary and analysis. All summary and analysis of the data will be 
performed using SAS® version 9.3 and/or WinNonLin Pro (Version 6.3 PhoenixTM, 
Pharsight®), or later. 
An explanation will be given for all missing, unused, and spurious data in the relevant 
sections of the CSR. 
10.1.8.2 Monitoring 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents 
(original documents), data and records. Direct access includes permission to examine, 
analyze, verify and reproduce any record(s) and report(s) that are important to the 
evaluation of the study. If the electronic medical record does not have a visible audit 
trail, the Investigator must provide the CRA with signed and dated printouts. In addition, 
the relevant site staff should be available for discussions at monitoring visits and 
between monitoring visits (e.g. by telephone). 
Study monitors/CRAs will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; to monitor drug accountability and collect completed paper CRF pages, if 
applicable, and verify that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
Monitoring details describing strategy (e.g. risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of non- 
compliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan. 
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator for a specified period required by local regulations, 

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ICH GCP, and/or Regulation (EU) No 536/2014 after study completion, unless local 
regulations or institutional policies require a longer retention period. 
U.S Federal laws require that an Investigator maintain all study records for the indication 
under investigation for 2 years following the date a Product Licensing Application is 
approved or, if no application is to be filed or if the application is not approved for such 
indication, until 2 years after the investigation is discontinued and the FDA is notified. 
European law require that the Investigator maintain all study records (excluding the 
patients’ medical files) for at least 25 years after completion or discontinuation of the 
study. 
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. 
The Sponsor assumes accountability for actions delegated to other individuals (e.g. 
CROs). 
10.1.8.3 Protocol Compliance 
The policy of BerGenBio is that no waivers will be issued. 
Deviations from the protocol should be avoided. If deviations do occur, the Investigator 
must inform the CRA without delay and the implications of the deviation must be 
reviewed and discussed. 
Deviations must be documented and explained in a protocol deviation by capturing a 
brief description of the deviation and stating the reason, date, and the action(s) taken. 
Serious Breach of GCP 
The Principal Investigator must promptly provide the Sponsor or Sponsor’s 
representative, i.e., the CRA, with reports on any serious breaches of the protocol, GCP, 
EU Clinical Trial Directive, or any change that is likely to significantly affect the safety 
and rights of a subject, or the reliability and robustness of the data generated in the 
study. 
10.1.8.4 Study Audit 
The Sponsor, Sponsor representative, or external regulatory agency may at any time 
during or after completion of the study conduct a GCP audit at any trial site. Prior notice 
will be given to each site selected for audit in advance of a planned audit. 
10.1.8.5 Clinical Study Report 
The results of the study will be presented in an integrated CSR according to ICH 
guidelines. 
10.1.9 
Source Documents 
• 
All data entered in the eCRF must be verifiable in source documentation other 
than the eCRF. 
• 
Source documents provide evidence for the existence of the subject and 
substantiate the integrity of the data collected. Source documents are filed at the 
site. 
• 
Data reported on the paper SAE CRF or entered in the eCRF that are transcribed 
from source documents must be consistent with the source documents, or the 

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discrepancies must be explained. The Investigator may need to request previous 
medical records or transfer records. Also, current medical records must be 
available. 
• 
It must be possible to verify subject’s medical history in source documents, such 
as subject’s medical record. 
• 
The Investigator must document any attempt to obtain external medical 
information by noting the date when information was requested, and who was 
contacted. 
• 
Definition of what constitutes source data can be found in a source document 
agreement at each site. There will only be one source document defined at any 
time for any data element. 
10.1.10 Study and Site Start 
Study start is defined by the first subject entering the screening period, however, the 
First Subject In (FPI) is when the first subject receives the first dose of study 
medication. 
10.1.11 Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the Sponsor. Study sites will be 
closed upon study completion. A study site is considered closed when all required 
documents and study supplies have been collected and a study-site closure visit has 
been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the Investigator 
• 
Discontinuation of further study intervention development 
If the clinical study is prematurely terminated or suspended, the Sponsor shall promptly 
inform the Investigators, the IECs/IRBs, the regulatory authorities, and any contract 
research organization used in the clinical study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The Investigator 
shall promptly inform all subjects, as appropriate, and should ensure appropriate subject 
therapy and/or follow-up. 
A pre-planned interim analysis will be conducted to support decision making and based 
on this interim analysis, a dose level may be dropped due to futility, or the study 
stopped, see Section 9.5. 
10.1.12 Responsibilities 
The Investigator is accountable for the conduct of the clinical study at his/her site and 
must ensure adequate supervision of the conduct of the clinical study at the site. If any 
tasks are delegated, the Investigator must maintain a log of appropriately qualified 
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must ensure that there is adequate and documented training for all staff participating in 
the conduct of the clinical study. It is the Investigator’s responsibility to supervise the 
conduct of the clinical study and to protect the rights, safety, and wellbeing of the 
subjects. 
A qualified physician, who is an Investigator or a sub-Investigator for the clinical study, 
must be responsible for all study-related medical decisions. 
The Investigator is responsible for filing essential documents (i.e. those documents 
which individually and collectively permit the evaluation of the conduct of a clinical study 
and the quality of the data produced) in the Investigator trial master file. The 
documents, including the subject identification code list must be kept in a secure locked 
facility so that no unauthorized persons can get access to the data. 
The Investigator will take all necessary technical and organizational measures to prevent 
accidental or wrongful destruction, loss or deterioration of data. The Investigator will 
prevent any unauthorized access to data or any other processing of the data in 
accordance with applicable law. The Investigator must be able to provide the necessary 
information or otherwise demonstrate to the Sponsor that such technical and 
organizational measures have been taken. 
During any period of unavailability, the Investigator must delegate responsibility for 
medical care of subjects to a specific qualified physician who will be readily available to 
ensure continued care of the study subjects during that time. 
If the Investigator is no longer able to fulfill the role as Investigator (e.g. if he/she 
moves or retires), a new Investigator will be appointed in consultation with the Sponsor. 
The Investigator and other site personnel must have sufficient English skills according to 
their assigned task. 
10.1.13 Publication Policy 
• 
The results of this clinical study may be published or presented at scientific 
meetings. If this is foreseen. The Sponsor will review all publications before 
submission. This allows the Sponsor to protect proprietary information and to 
provide comments. 
• 
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 multi center studies only in their entirety and not 
as individual site data. In this case, a coordinating Investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
• 
No confidential information shall be disclosed to others without prior written 
consent from the Sponsor. Such information shall not be used except in the 
performance of this clinical study. 
One Investigator (known as the Principal Investigator) will be appointed by BGB to 
review and sign the CSR (signatory Investigator) on behalf of all participating 
Investigators. 

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If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study medication, additional evaluation should 
be considered. 
Females in the following categories are not considered WOCBP 
1. Premenarchal 
2. Pre-menopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
Females with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Müllerian agenesis, androgen insensitivity), Investigator discretion 
should be applied to determining clinical study entry. 
Note: Documentation can come from the site personnel’s: review of the subject’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as amenorrhea for 12 months without an 
alternative medical cause. 
• 
A high 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). However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen 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. 
Male Subjects 
For this trial, male subjects will be considered to be of reproductive potential unless 
permanently sterile by bilateral orchidectomy. 
Contraception Guidance: 
To participate in the study, subjects (both male and female) of reproductive potential 
must be willing to practice highly effective methods of contraception throughout the 
study and for 4 months after the last dose of pembrolizumab, 6 months after the last 
dose of chemotherapeutic agents or 30 days after the last dose of bemcentinib 
whichever is the later by complying with one of the following highly effective methods‡: 
• 
Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation: 
o 
Oral 
o 
Intravaginal 
o 
Transdermal 

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• 
Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o 
Oral 
o 
Injectable 
o 
Implantable 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner is a highly effective birth control method provided that 
partner is the sole sexual partner of the WOCBP trial participant and that the 
vasectomized partner has received medical assessment of the surgical success. 
• 
Practice abstinence from heterosexual activity† 
†Abstinence (relative to heterosexual activity) can be used as the sole method of 
contraception if it is consistently employed as the patient’s preferred and usual lifestyle 
and if considered acceptable by local regulatory agencies and IRB/ IECs. Periodic 
abstinence e.g., calendar, ovulation, symptothermal, post-ovulation methods, etc. and 
withdrawal are not acceptable methods of contraception. 
‡If a contraceptive method listed above is restricted by local regulations/guidelines, then 
it does not qualify as an acceptable method of contraception for patients participating at 
sites in this country/region. 
Male subjects should also refrain from donating sperm during this period. Men should be 
advised to seek advice on sperm preservation before starting therapy due to the 
possibility of irreversible infertility after treatment with carboplatin. 
Female subjects should be advised that they may experience amenorrhea (absence of 
menstrual periods) during treatment with carboplatin, and this effect may be 
irreversible. 
Subjects should be informed that taking the study medication may involve unknown 
risks to the fetus (unborn baby) if pregnancy were to occur during the study. 
If there is any question that a subject of childbearing potential will not reliably comply 
with the requirements for contraception, that patient should not be entered into the 
study. 
Collection of Pregnancy Information 
If a partner of a subject enrolled in the clinical study become pregnant, he must 
discontinue treatment immediately. 
The Investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor preferably within (24 hours) of 
learning of the partner’s pregnancy. The female partner will also be followed to 
determine the outcome of the pregnancy. Information on the status of the 
mother and child will be forwarded to the Sponsor. Generally, the follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any 

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termination of the pregnancy will be reported regardless of fetal status (presence 
or absence of anomalies) or indication for the procedure. 
Female subjects who become pregnant 
• 
The Investigator will collect pregnancy information on any female subject who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to the CRO within (24-hours) of 
learning of a subject’s pregnancy. 
• 
The subject will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the subject and the neonate, and 
the information will be forwarded to the Sponsor. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth 
(occurring at >22 weeks gestational age) is always considered to be an SAE and 
will be reported as such. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
product by the Investigator will be reported to the Sponsor as described in 
Section 10.3.4. While the Investigator is not obligated to actively seek this 
information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting. 
• 
Any female subject who becomes pregnant while participating in the study will 
discontinue treatment immediately. 
10.5 
Appendix 5: Genomics 
Analysis of DNA and RNA 
• 
Liquid (blood) and solid tumor biopsy samples of consenting patients will be 
collected and processed for isolation of genomic material in a Sponsor designated 
laboratory. DNA isolated from liquid and/or solid tumor biopsies may be 
sequenced for mutations and additionally may be sequenced for gene expression 
(Li et al., 2022). 
• 
In the phase 1b part of the study, samples will be collected from all subjects and 
may be sequenced retrospectively to further understand the clinical data. 
• 
In the phase 2a part of the study, liquid and/or solid tumor biopsies will be 
subjected to DNA sequencing during screening to select patients positive for 
STK11 mutations for enrollment and treatment with the study drugs. 
• 
DNA samples will be analyzed for presence of mutations in genes including STK11 
and associated pathways in NSCLC. Additional analyses may be conducted if it is 
hypothesized that this may help further understand the clinical data. 
• 
If patients consent to future research, DNA and RNA samples will be used for 
research related to AXL inhibitors such as bemcentinib or NSCLC and related 
diseases. They may also be used to develop tests/assays including diagnostic 

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tests related to AXL inhibitors and NSCLC and related diseases. Genetic research 
may consist of the analysis of one or more candidate genes or analysis of the 
entire genome or transcriptome. 
• 
The results of genetic analyses may be reported in the CSR and/or in a separate 
study report. 
• 
All DNA/RNA will be stored securely in a Sponsor designated laboratory with 
adequate measures to protect confidentiality. 
• 
Following completion of the study, all leftover materials will be stored in a 
regional ethical committee approved biobank for the period approved by the 
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10.6 
Appendix 6: Drugs that Prolong QT and Induce Torsades de Pointes 
See table below for a list of drugs that may cause Torsades de Pointes. 
Table 16 Overview of Drugs that Prolong QT and Induce Torsades de Pointes 
 
Generic Name 
Brand Names 
Drug Class 
Therapeutic Use 
Escitalopram 
Cipralex, Lexapro, 
Nexito, Anxiset-E, 
Exodus, Esto, 
Seroplex, Elicea, 
Lexamil, Lexam, 
Entact, Losita, 
Reposil, Animaxen, 
Esitalo, Lexamil 
Antidepressant, SSRI 
Depression (major), 
anxiety disorders 
Flucanazole 
Diflucan, Trican 
Antifungal 
Fungal infection 
Probucol 
(Removed from US 
Market) 
Lorelco 
Antilipemic 
Hypercholesterolemia 
Gatifloxacin 
(Removed from US 
Market) 
Tequin 
Antibiotic 
Bacterial infection 
Haloperidol 
Haldol, Aloperidin, 
Bioperidolo, Brotopon, 
Dozic, Duraperidol, 
Einalon S, Eukystol, 
Halosten, Keselan, 
Linton, Peluces, 
Serenace, Serenase, 
Sigaperidol 
Antipsychotic 
Schizophrenia, 
agitation 
Sertindole 
(Only on Non-US 
Market) 
Serdolect, Serlect 
Antipsychotic, atypical 
Schizophrenia, 
anxiety 
Astemizole 
(Removed from US 
Market) 
Hismanal 
Antihistamine 
Allergic rhinitis 
Arsenic trioxide 
Trisenox 
Anti-cancer 
Cancer (leukemia) 
Sparfloxacin 
(Removed from US 
Market) 
Zagam 
Antibiotic 
Bacterial infection 
Citalopram 
Celexa, Cipramil 
Antidepressant, SSRI 
Depression 
Levofloxacin 
Levaquin, Tavanic 
Antibiotic 
Bacterial infection 
Moxifloxacin 
Avelox, Avalox, 
Avelon 
Antibiotic 
Bacterial infection 
Ibutilide 
Corvert 
Antiarrhythmic 
Arrhythmia 
Droperidol 
Inapsine, Droleptan, 
Dridol, Xomolix 
Antipsychotic / 
Antiemetic 
Anesthesia (adjunct), 
nausea 
Chlorpromazine 
Thorazine, Largactil, 
Megaphen 
Antipsychotic / 
Antiemetic 
Psychosis, nausea, 
many others 

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Generic Name 
Brand Names 
Drug Class 
Therapeutic Use 
Thioridazine 
Mellaril, Novoridazine, 
Thioril 
Antipsychotic 
Schizophrenia 
Clarithromycin 
Biaxin, Prevpac 
Antibiotic 
Bacterial infection 
Dronedarone 
Multaq 
Antiarrhythmic 
Arrhythmia 
Sevoflurane 
Ultane, Sojourn 
Anesthetic, general 
Anesthesia 
Chloroquine 
Aralen 
Antimalarial 
Malaria 
Domperidone 
(Only on Non-US 
Market) 
Motilium, Motillium, 
Motinorm Costi, 
Nomit 
Antiemetic 
Nausea, vomiting 
Mesoridazine 
(Removed from US 
Market) 
Serentil 
Antipsychotic 
Schizophrenia 
Cocaine 
Cocaine 
Local anesthetic 
Anesthesia (topical) 
Roxithromycin 
(Only on Non-US 
Market) 
Rulide, Xthrocin, 
Roxl-150, Roxo, 
Surlid, Rulide, 
Biaxsig, Roxar, 
Roximycinv, 
Roxomycin, Rulid, 
Tirabicin, Coroxin 
Antibiotic 
Bacterial infection 
Ondansetron 
Zofran, Anset, 
Ondemet, Zuplenz, 
Emetron, Ondavell, 
Emeset, Ondisolv, 
Setronax 
Antiemetic 
Nausea, vomiting 
Sotalol 
Betapace, Sotalex, 
Sotacor, Sotalol-AF 
Antiarrhythmic 
Arrhythmia 
Quinidine 
Quinaglute, Duraquin, 
Quinact, Quinidex, 
Cin-Quin, Quinora 
Antiarrhythmic 
Arrhythmia 
Procainamide 
Pronestyl, Procan 
Antiarrhythmic 
Arrhythmia 
Pimozide 
Orap 
Antipsychotic 
Psychosis, Tourette’s 
Disorder 
Pentamidine 
Pentam 
Antifungal 
Fungal infection 
(Pneumocystis 
pneumonia) 
Halofantrine 
(Only on Non-US 
Market) 
Halfan 
Antimalarial 
Malaria 
Azithromycin 
Zithromax, Zmax 
Antibiotic 
Bacterial infection 
Vandetanib 
Caprelsa 
Anti-cancer 
Cancer (thyroid) 
Flecainide 
Tambocor, Almarytm, 
Apocard, Ecrinal, 
Flécaine 
Antiarrhythmic 
Arrhythmia 

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Generic Name 
Brand Names 
Drug Class 
Therapeutic Use 
Ciprofloxacin 
Cipro, Cipro-XR, 
Neofloxin 
Antibiotic 
Bacterial infection 
Cisapride 
(Removed from US 
Market) 
Propulsid 
GI stimulant 
Increase GI motility 
Disopyramide 
Norpace 
Antiarrhythmic 
Arrhythmia 
Dofetilide 
Tikosyn 
Antiarrhythmic 
Arrhythmia 
Methadone 
Dolophine, Symoron, 
Amidone, Methadose, 
Physeptone, 
Heptadon 
Opioid agonist 
Narcotic dependence, 
pain 
Levomethadyl acetate 
(Removed from US 
Market) 
Orlaam 
Opioid agonist 
Narcotic dependence 
Erythromycin 
E.E.S., Robimycin, 
Emycin, Erymax, Ery- 
Tab, Eryc Ranbaxy, 
Erypar, Eryped, 
Erythrocin Stearate 
Filmtab, Erythrocot, 
E-Base, Erythroped, 
Ilosone, MY-E, 
Pediamycin, 
Abboticin, Abboticin- 
ES, Erycin, PCE 
Dispertab, 
Stiemycine, Acnasol, 
Tiloryth 
Antibiotic 
Bacterial infection, 
increase GI motility 
Bepridil 
Vascor 
Antianginal 
Angina Pectoris (heart 
pain) 
Amiodarone 
Cordarone, Pacerone, 
Nexterone 
Antiarrhythmic 
Arrhythmia 
Terfenadine 
(Removed from US 
Market) 
Seldane 
Antihistamine 
Allergic rhinitis 
Anagrelide 
Agrylin, Xagrid 
Phosphodiesterase 3 
inhibitor 
Thrombocythemia 
Sulpiride 
(Only on Non-US 
Market) 
Dogmatil, Dolmatil, 
Eglonyl, Espiride, 
Modal, Sulpor 
Antipsychotic, atypical 
Schizophrenia 
Grepafloxacin 
(Removed from US 
Market) 
Raxar 
Antibiotic 
Bacterial infection 
Hydroxychloroquine 
Plaquenil, Quineprox 
Antimalarial, Anti- 
inflammatory 
Malaria, SLE, 
rheumatoid arthritis 
Cilostazol 
Pletal 
Phosphodiesterase 3 
inhibitor 
Intermittent 
claudication 

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Generic Name 
Brand Names 
Drug Class 
Therapeutic Use 
Propofol 
Diprivan, Propoven 
Anesthetic, general 
Anesthesia 
Donepezil 
Aricept 
Cholinesterase 
inhibitor 
Dementia 
(Alzheimer’s Disease) 
Papaverine HCl 
(Intra-coronary) 
Vasodilator, Coronary 
Diagnostic adjunct 
Levomepromazine 
(Methotrimeprazine) 
(Only on Non-US 
Market) 
Nosinan, Nozinan, 
Levoprome 
Antipsychotic 
Schizophrenia 
Oxaliplatin 
Eloxatin 
Anti-cancer 
Cancer 
Terodiline 
(Only on Non-US 
Market) 
Micturin, Mictrol 
Muscle relaxant 
Bladder spasm 
Levosulpiride 
(Only on Non-US 
Market) 
Lesuride, Levazeo, 
Enliva 
Antipsychotic 
Schizophrenia 
Sultopride 
(Only on Non-US 
Market) 
Barnetil, Barnotil, 
Topral 
Antipsychotic, atypical 
Schizophrenia 
Terlipressin 
(Only on Non-US 
Market) 
Teripress, Glypressin, 
Terlipin, Remestyp, 
Tresil, Teriss 
Vasoconstrictor 
Septic shock 
Ibogaine 
(Only on Non-US 
Market) 
Psychedelic 
Narcotic dependence, 
unproven efficacy 
Chlorprothixene 
(Only on Non-US 
Market) 
Truxal 
Antipsychotic 
Schizophrenia 
Aclarubicin 
(Only on Non-US 
Market) 
Aclacin, 
Aclacinomycine, 
Aclacinon, Aclaplastin, 
Jaclacin 
Anti-cancer 
Cancer 
Hydroquinidine 
(Dihydroquinidine) 
(Only on Non-US 
Market) 
Serecor 
Antiarrhythmic 
Arrhythmia 
Nifekalant 
(Only on Non-US 
Market) 
Shinbit 
Antiarrhythmic 
Arrhythmia 
Cesium Chloride 
Energy Catalyst 
toxin 
Alternative therapy 
cancer 
Meglumine 
antimoniate 
(Only on Non-US 
Market) 
Glucantime 
Antiparasitic 
Leishmaniasis 

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Generic Name 
Brand Names 
Drug Class 
Therapeutic Use 
Mobocertinib 
Exkivity 
Tyrosine kinase 
inhibitor 
Cancer (Lung) 
Source: https://crediblemeds.org 
 
10.7 
Appendix 7: Prohibited Medications During the Study 
See table below for a list of prohibited medications. 
Table 17 Prohibited Medications During the Study 
 
Live or live-attenuated vaccine 
Yellow fever vaccine 
Chelating agents – Deferasirox, Trientine, Deferiprone, Deferoxamine, 
EDTA derivatives and Succimer 
 
 
 
 
 
10.8 
Appendix 8: Eastern Cooperative Oncology Group Performance Status 
 
Grade 
ECOG Performance Status 
0 
Fully active. Able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature (e.g., light housework, office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead. 
Source: Oken et al., 1982 

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10.9 
Appendix 9: Abbreviations and Definitions of Terms 
 
1L 
First line 
2L 
Second line 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
AST 
Aspartate aminotransferase 
AUC5 
Area under the concentration– time curve, 5 mg per milliliter per minute 
BBB 
Blood-brain barrier 
Bem 
Bemcentinib 
BGB 
BerGenBio ASA 
BSA 
body surface area 
C1D1 
Cycle 1 Day 1 
C1D2 
Cycle 1 Day 2 
C1D8 
Cycle 1 Day 8 
C1D15 
Cycle 1 Day 15 
CIT 
Chemo-immunotherapy 
CPI 
Checkpoint inhibitor 
CRA 
Clinical Research Associate 
CrCl 
Creatinine clearance 
CRF 
Case report form 
CRO 
Contract research organization 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DC 
Doublet chemotherapy 
DCR 
Disease control rate 
DLT(s) 
Dose limiting toxicity(ies) 
DOR 
Duration of response 
DSMB 
Data safety monitoring board 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EMT 
Epithelial-mesenchymal transition 
EoT 
End of Treatment 
FDA 
US Food and Drug Administration 

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FDAAA 
FDA Amendments Act 
FFPE 
Formalin-fixed, paraffin embedded 
FN 
Febrile neutropenia 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HR 
Hazard ratio 
HRT 
Hormone replacement therapy 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of technical requirements for 
pharmaceuticals for human use 
IEC 
Independent ethics committee 
IFN 
Interferon 
ILS 
Investigator-led study 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional review board 
iRECIST 
Immune Response Evaluation Criteria in Solid Tumors 
IV 
intravenous 
LFT 
Liver function test 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
mPFS 
Median progression free survival 
mOS 
Median overall survival 
MiST 
Mesothelioma stratified therapy 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger ribonucleic acid 
MUGA 
Multigated acquisition 
NGS 
Next generation sequencing 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
ORR 
Objective response rate 
OS 
Overall survival 
PCD 
Primary completion date 
PD-L1 
Programmed death-ligand 1 

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PFS 
Progression free survival 
PK 
Pharmacokinetics 
PK-PD 
Pharmacokinetic-pharmacodynamic 
PT 
Prothrombin time 
Q3W 
Every 3 weeks 
QTc 
Corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RECIST 
Response Evaluation Criteria in Solid Tumours 
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 
SOC 
Standard of care 
STK11m 
Serine/threonine kinase 11 mutation 
STK11wt 
Serine/threonine kinase 11 wild type 
SUSAR 
Suspected unexpected serious adverse reaction 
T3 
Triiodothyronine 
T4 
Thyroxine 
TdP 
Torsades de pointes 
TME 
Tumor microenvironment 
TNBC 
Triple negative breast cancer 
TPS 
Tumor proportion score 
TSH 
Thyroid stimulating hormone 
US 
United States 
WOCBP 
Woman of childbearing potential 

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