A Phase II Multi Center Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated Advanced Adenocarcinoma of the Lung
Phase: PHASE2
Conditions: Lung Cancer Metastatic, NSCLC Stage IV, Adenocarcinoma of Lung
Sponsor: BerGenBio ASA

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
1 of 126 
 CLINICAL STUDY PROTOCOL 
Investigational Product:  
BGB324; pembrolizumab 
Sponsor:  
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen, Norway 
Protocol Number: 
BerGenBio ASA: BGBC008 
Merck & Co: MK-3475 PN-531 
Phase: 
Phase II 
Protocol Title: 
A Phase II Multi-Center Study of BGB324 in 
Combination with Pembrolizumab in Patients with 
Previously Treated Advanced Adenocarcinoma of 
the Lung 
IND Number: 
IND-124645 
EudraCT Number: 
2016-003609-32 
Version and Date: 
Version 11.0 (Global)/26 January 2022 
Version Table: 
Final, Version 1.0 
02 November 2016 
Versions 2.0 and 3.0 (EU-Spain) not created.   
Version 3.0 (EU-UK, EU-NO, USA) not issued 
Version numbers aligned across study 
- 
Version 4.0 (EU, NO, USA, Spain) 
Version numbers aligned across study 
13 June 2017 
Version 5.0 (Global) 
31 August 2018 
Version 6.0 (Global) 
04 December 2018 
Version 7.0 (Global) 
29 April 2019 
Version 8.0 (Global) 
07 October 2019 
Version 9.0 (Global) 
09 April 2020 
Version 10.0 (Global) 
07 October 2020 
CONFIDENTIAL STATEMENT: 
Information in this protocol is confidential and should not be disclosed, other than to those 
directly involved in the execution or the ethical/regulatory review of the study, without 
written authorization from BerGenBio ASA 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
Protocol Approval Signatures 
Sponsor's Approval: 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
This study will be conducted in compliance with International Council for Ha1monisation 
(ICH) guidelines on Good Clinical Practice (GCP), the Declaration of Helsinki (with 
amendments), and in accordance with local legal and regulato1y requirements. 
This protocol has been approved by BerGenBio ASA. 
Signature: 
Date: 
BerGenB10 ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Email: 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
C
Confldentlal 
2 of 126 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
3 of 126 
Investigator’s Approval: 
I have read this protocol and agree that it contains all the necessary details for carrying out this 
study. I will conduct the study as described and will complete the study within the time 
designated. I verify that I am suitably qualified by education, scientific and medical training 
and experience to conduct the study. Documentation of my qualifications and professional 
affiliations are contained in my up-to-date curriculum vitae. 
I will provide the supplied copies of the protocol, including future protocol amendments, and 
all information relating to non-clinical, and clinical experience when available in updated 
editions of the Investigator’s Brochure (IB), to all staff in my unit involved in the conduct of 
this study. I will discuss this material with them to ensure that they are fully conversant with 
medical treatment and study design, and that they will handle the data and information 
generated in the study confidentially. 
I will conduct the study in accordance with Good Clinical Practice (GCP), the Declaration of 
Helsinki, and the moral, ethical and scientific principles that justify medical research. The 
study will be conducted in accordance with the relevant laws and regulations relating to clinical 
studies and the protection of patients. All patients 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 (BerGenBio) and the Ethics 
Committee (EC) for this study. I will supply BerGenBio with any material written by myself 
e.g., summary of study, which is given to the EC in support of the application.
Where applicable, the patient information contained in clinic records, reports and manuscripts 
will be transcribed to the case report forms (the case report form may be the original source 
document for specified items). Either I or an appointed person will attest to the authenticity of 
the data and accuracy and completeness of the transcription by signing the case report form. 
I agree to the audit and monitoring procedures that involve verification of such study records 
against original records. 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 BerGenBio and are confidential. I will supply BerGenBio (or their delegates) with the study 
data in such a way that the patient cannot be personally identified. 
Investigator: ____________________________ 
____________________________ 
Signature 
Date 
Print Name: 
_____________________________________________________________________ 
Institution Name: ____________________________________________________________ 
Institution Address: 
___________________________________________________________ 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
4 of 126 
OTHER CONTACT INFORMATION 
Full contact details for each Investigational site, the Sponsor (including medical out-of-hours 
contact number), and key coordinating and operational personnel will be maintained in the 
Trial Master File (TMF) and in each Site Study File. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
PROTOCOL SYNOPSIS 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Protocol No: BGB324 BGBC008 / MK-3475 PN-531 
Study Title: A Phase II Multi-Center Study ofBGB324 in Combination with Pembrolizumab 
in Patients with Previously Treated Advanced Adenocarcinoma of the Lung 
Investigational Products: 
•
BGB324 (now called by the INN name bemcentinib throughout the protocol): a
potent selective small molecule inhibitor of Axl, a surface membrane protein
kinase receptor
•
Pembrolizumab: a humanized monoclonal antibody against the programmed death
receptor-I (PD-1)
Phase of Development: Phase II 
Number of Sites: Up to approximately 20 sites. Additional sites may be added as required to 
meet the enrolment needs of the clinical trial. 
Number of Patients: 
Up to 48 evaluable patients will be enrolled in cohort A, 29 evaluable patients in cohort B and 
29 evaluable patients in coho1t C. Approximately 133 patients will be screened in order to 
identify up to 106 patients who meet all of the inclusion and exclusion criteria and who are 
evaluable for response. This assumes a 25% screen failure rate, given the need for patients to 
provide a fresh tissue biopsy sample. 
Study Objectives and Endpoints 
Table 1: Study Objectives and Endpoint (Assessment) 
Objective 
Endpoint (Assessment) 
Primary: 
•
To assess the anti-tumor activity of bemcentinib 
•
and pembrolizumab when given in combination
Objective response rate (complete response and 
partial response) 
Secondary: 
•
To assess the safety of bemcentinib and 
•
pembrolizumab when given in combination
The number and frequency of adverse events; 
assessment of safety laboratory parameters, vital 
signs, and Electrocardiogram (ECGs) 
•
To further assess the anti-tumor activity of the
combination ofbemcentinib and pembrolizumab
•
To include Disease Control Rate, Duration of
•
To evaluate the pharmacokinetic (PK) profile of •
bemcentinib when given with pembrolizumab.
Response, Progression-free Survival, median
Overall Survival, and 12-month Overall Survival
Assessment of pharmacokinetic (PK) variables
including Cm.x, AUC, and t½ 
Exploratory 
•
To assess relevant biomarkers
•
To assess PD-LI and Axl expression in patients
with adenocarcinoma of the lung
•
To assess any correlation or association between
expression level of PD-LI and Ax1 and anti-tumor
outcomes such as ORR
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
5 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
Objective 
Study Design 
Endpoint (Assessment) 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
•
Assessment of relevant biomarkers in tumor and
blood which support immune modulation and Axl
signaling
•
Developing a radiomic signature as a response
prognostic biomarker
This is an open-label, multi-center, single aim, phase II sh1dy to assess the anti-himor activity 
and safety of bemcentinib when given in combination with pembrolizumab in patients with 
previously treated, advanced adenocarcinoma of the lung. 
The sh1dy will enroll three cohorts of patients with previously treated, advanced 
adenocarcinoma of the lung: Cohort A will consist of patients who received a maximum of one 
prior line of platintim-containing chemotherapy and no prior immunotherapy of any kind. 
Cohort B will consist of patients who received a maximtim ofone prior line of an anti-PD-(L)l 
therapy (monotherapy). Cohort C will consist of patients who received a maximum of one prior 
line of therapy with an anti--PD-(L)l therapy in combination with a platinum-containing 
chemotherapy. 
Pembroliztimab has not previously been combined with bemcentinib in patients (in any 
indication) and therefore, in coho1t A, a safety nm-in will include a total of 12 patients. The 
internal Data Review Committee (DRC) will conduct a review of the safety data from the first 
6 patients who have had the potential to be followed for at least 6 weeks (minimtim 2 cycles), 
and then again after a further 6 patients (12 patients in total) have had the potential to be 
followed for at least 6 weeks. The DRC will consider the emerging safety profile, together with 
the number of patients requiring a bemcentinib dose reduction and the number of patients 
requiring either bemcentinib or pembroliztimab or both to be permanently discontinued. The 
DRC will consider whether a revised bemcentinib dose (dose level -1) is appropriate for new 
patients entering the shldy. 
Cohort A will utilize a 2-stage, single-aim, Simon's 2-stage design1 with a single interim 
(Stage 1) analysis and a final (Stage 2) analysis. The interim (Stage 1) analysis will be 
conducted for DRC when 22 patients are evaluable (EE) for Objective Response Rate (ORR). 
If 3 or fewer responses are observed in up to 22 patients, the cohort will be te1minated in favor 
of the null hypothesis for futility, and no ftuther paiticipants will be recruited. When at least 4 
patients have an observed response at the interim analysis, up to a ftuther 26 patients may be 
evaluated (Evaluable for Efficacy (EE)), for a total of 48 evaluable (EE) patients (see Section 
8.1), taking the overall risk-benefit of the combination into consideration. 
Recmitment for coho1t A will be halted after 22 evaluable patients have been entered and 
whilst the Stage 1 interim analysis is conducted for DRC review. Recmitment will 
recommence if the decision is made to continue to the maximum of 48 (EE) evaluable patients. 
An additional cohort B will assess the anti-tumor activity and safety of bemcentinib when 
given in combination with pembrolizumab in patients with advanced adenocarcinoma of the 
lung with a maximum of one prior line of an anti-PD-(L) 1 therapy (monotherapy). 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
6 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
7 of 126 
Cohort B will utilize a single-arm, Simon’s 2-stage design with an interim (Stage 1; null 
hypothesis for futility) and an interim (Stage 2; once all patients have been treated and/or 
followed up for at least 12 months) analysis. The interim (Stage 1) analysis will be conducted 
for DRC review when 13 patients are evaluable for ORR. If 0 responses are observed in up to 
13 patients, the cohort will be terminated in favor of the null hypothesis for futility, and no 
further participants will be recruited. When at least 1 patient has an observed response at the 
interim (Stage 1) analysis, up to a further 16 patients may be evaluated, for a total of 29 (EE) 
patients (see Section 8.1), taking the overall risk-benefit of the combination into consideration. 
An additional cohort C will assess the anti-tumor activity and safety of bemcentinib when 
given in combination with pembrolizumab in patients with advanced adenocarcinoma of the 
lung with a maximum of one prior line of an anti-PD-(L)1 therapy in combination with a 
platinum-containing chemotherapy.  
Cohort C will utilize a single-arm, Simon’s 2-stage design with an (null hypothesis for futility) 
interim (Stage 1; null hypothesis for futility) and an interim (Stage 2; once all patients have 
been treated and/or followed up for at least 12 months) analysis. The interim (Stage 1) analysis 
will be conducted for DRC review when 13 patients are evaluable for ORR. If 0 responses are 
observed in up to 13 EE patients, the cohort will be terminated in favor of the null hypothesis 
for futility, and no further participants will be recruited. When at least 1 patient has an observed 
response at the interim analysis, up to a further 16 patients may be evaluated, for a total of 29 
EE patients (see Section 8.1), taking the overall risk-benefit of the combination into 
consideration. 
Figure 1: Schematic Diagram of the Study Design 
Multi-arm study in 2L Non-small cell lung cancer (NSCLC) of selective AxL inhibitor 
bemcentinib in combination with pembrolizumab 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Bemcentinib will be administered orally once daily. On the first 3 days of administration, the 
bemcentinib dose will be a 'loading' dose of 400 mg on Days 1, 2 and 3. From Day 4 onwards, 
patients will receive a daily dose of 200 mg daily. If the DRC recommend dose level -1 for 
new pat°fter or during the safety nm± dose ofbemcentinib will reduce to a loading 
dose of- on Days 1, 2 and 3 and to- from Day 4 onwards. 
A fixed dose of 200 mg pembrolizumab will be given by intravenous (IV) infusion over 
30 minutes every 3 weeks in all patients. The 3-weekly dosing pembrolizumab dosing schedule 
will be used to define 3-week treatment cycles throughout the treatment period of the study. 
The bemcentinib and pembrolizumab dose levels selected for this study are summarized in 
Table 2. 
Table 2: Bemcentinib and Pembrolizumab Dosing 
Loading Dose: 
Daily Dose: 
F1·equency 
Route of 
Bemcentinib: 
Days 1, 2 & 3 
Day 4 onwards 
administration 
-
-
- -
• 
- -
- -
• 
Dose 
Regimen 
F1·equency 
Route of 
administration 
Pembl'Olizumab 
Day 1 of each cycle 
200mg 
Every 
IV 
(3-week cycles) 
3 weeks 
Dosing of both dmgs will commence on Day 1. On days when both bemcentinib and 
pembrolizumab are given, pembrolizumab will be given first and patients will be observed for 
1 hour for infusion or other adverse events (AEs). Bemcentinib may then be administered. 
Bemcentinib and pembrolizumab will be given until disease progression (note that in the 
absence of clinical deterioration, treatment can continue and disease progression should be 
confumed after 4 weeks) or until an tmacceptable toxicity has occuned which necessitates 
treatment withdrawal (Section 6.6), or until 106 weeks (35 cycles), equivalent to 24 
calendar months. If it is decided at the Stage 1 interim analysis of any cohort that the 
cohort is to be closed for recruitment, then pa1ticipants who have stable disease, even in the 
absence of pa1tial response (PR) or complete response ( CR), will continue to be treated. 
NB: Paiticipants who are still on study treatment after 35 cycles and continue to show benefit 
from the sh1dy treatment will be offered access to bemcentinib (e.g., under expanded excess 
program or roll over sh1dy) outside the shldy, after discussion with the sponsor, prior to study 
closure. 
Patients who discontinue bemcentinib treatment (for reasons other than disease progression) 
may be able to continue with pembrolizumab (monotherapy) until 106 weeks (that is, 
35 completed cycles ofpembrolizumab, equivalent to 24 calendar months). 
Patients who discontinue pembrolizumab (for reasons other than disease progression) may be 
able to continue with bemcentinib (monotherapy) upon approval by the Sponsor until study 
closure. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
8 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
9 of 126 
 
If a tumor assessment scan is suggestive of progressive disease, but the patient has an absence
of clinical deterioration, a confirmatory scan after 4 weeks (this may be an unscheduled scan)
will be made in order to rule out a pseudo or false progression caused by an inflammatory 
immune response. In the absence of clinical deterioration, treatment with both bemcentinib 
and pembrolizumab can continue until disease progression is confirmed. 
As per RECIST 1.12, objective response should be confirmed by a repeat scan performed at 
least 4 weeks later. 
For the safety run-in, a DRC, consisting of Principal Investigators, the Sponsors’ medical 
monitors (BerGenBio and Merck), and invited experts as required, will review all patient safety 
data after 6 patients have been enrolled and followed up for 6 weeks (2 cycles), and then again 
after a further 6 patients (total 12 patients) have had the potential to be followed for 6 weeks. 
At each of these safety reviews, the DRC will consider the rate of bemcentinib dose reductions 
and the rate of permanent discontinuation from bemcentinib and/or pembrolizumab. The DRC 
will consider if a revised dose (dose level -1) for bemcentinib is appropriate. 
Additionally, a review of emerging safety data from the whole bemcentinib program will be 
made 6-monthly. 
The Sponsor may request ad-hoc DRC meetings at any time during the study to assess the 
safety data and review the need for dose modifications. For more details on the dose 
modification rules for bemcentinib and pembrolizumab, please refer to Section 6.6.1 and 
Section 6.6.2. 
Study Procedures and Assessments 
Please refer to Schedule of Study Assessments - Table 4, Table 5, and Table 6 for full details 
of all study assessments. For patients who have stopped bemcentinib, but continue with 
monotherapy pembrolizumab, there will be an adjusted list of study assessments. 
The study will consist of a Screening period, Treatment period (made up of consecutive, 
3-week cycles), a Post Treatment Visit, and Follow-up Assessments. Patients must provide
informed consent prior to commencing the study screening procedures. All patients are
required to have a fresh (newly acquired) tumor biopsy taken at Screening and are required to
provide sufficient tumor specimens to enable both Axl kinase and PD-L1 expression to be
measured.
Tumor specimens are therefore to be submitted in sufficient quantity to allow for PD-L1 
immunohistochemistry (IHC) and Axl IHC analysis (see the Pathology Manual). Samples with 
limited tumor content (<100 viable tumor cells), cytology, cell block, decalcified or formalin 
fixed but previously frozen, frozen sample, plastic embedded, bone, bone marrow, clot and 
fine needle aspirates are inadequate for defining tumor PD-L1 and Axl status. 
Axl expression can only be obtained from a fresh (newly acquired) tumor tissue sample. PD-L1 
expression can be determined from either a fresh (newly acquired) or archival sample. In all 
cases, the tumor tissue must not have been previously irradiated. 
Different testing laboratories will be used for Axl kinase and PD-L1 expression. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
10 of 126 
The fresh (newly acquired) tumor tissue sample will be either newly obtained core needle 
biopsy (minimum gauge 18) or a newly obtained excisional biopsy.  
The following tumor tissue alternatives are available (all options require fresh tumor tissue 
sample); however, if there is insufficient fresh tumor tissue available, the 3rd option below 
allows the submission of archival tissue in addition to the fresh tissue sample:  
•
Where only a core needle biopsy is used, a minimum of 4 core (with 1-cm tumor in
each core) biopsy samples are required. These should be placed in formalin and
processed into 2 single paraffin embedded (FFPE) blocks (2 cores in one block and
2 cores in the other block) within 24-48 hours.
•
Alternatively, where only a newly obtained excisional biopsy sample is used, this
biopsy should be processed into 2 paraffin embedded (FFPE) blocks within 24-48
hours.
•
Alternatively, 2 core (with 1-cm tumor in each core) needle (fresh tumor) biopsies or a
single newly obtained excisional biopsy sample can be submitted (processed into one
FFPE block), together with either an archival (FFPE) tumor tissue block or a minimum
of 10 unstained slides each 5 µm cut from the archival tumor sample block.
If archival tumor tissue blocks are to be sent, it is suggested that a minimum of 10 unstained 
slides each 5 µm cut from the archival tumor sample block must be sent (rather than sending 
the whole archival block) and clearly labelled as having come from an archival block. 
The first dose of study drug must be administered within 4 weeks of commencing the Screening 
assessments. A tumor assessment scan by computed tomography (CT) (preferred method), or 
magnetic resonance imaging (MRI) of the chest, abdomen and pelvis is required during the 
Screening period. X-ray and bone scans can be used where appropriate (for example, for 
symptomatic sites that are negative on a bone scan) for disease status are required during the 
Screening period. 
Recording of AEs and concomitant medications, plus laboratory screens including ECGs will 
be performed at each study visit. During Cycle 1, patients will have study visits on Days 1, 2, 
3 and 4, then on Days 8 and 15. From Cycle 2 Day 1, study visits will be reduced to every 
3 weeks. 
ECG assessments will be performed in triplicate pre-dose and at 6 hours after the bemcentinib 
dose on Day 1, Cycle 1 and then repeated pre-bemcentinib dose on Days 2, 3 and 4 (Cycle 1) 
and then at every visit thereafter. 
Further tumor assessment scans will be performed in all patients every 9 weeks for the first 46 
weeks and then 12 weekly thereafter until progression (which may be confirmed). On each 
occasion, tumor assessments will include scans of the chest, abdomen and pelvis. Additional 
anatomy should be imaged based on signs and symptoms of individual patients. Disease 
response will be evaluated at these time points according to RECIST 1.12. If either or both of 
the study treatments are stopped for any reason other than confirmed progression, tumor 
assessment scans will continue every 12 weeks until confirmed progression. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
11 of 126 
Blood sampling for peripheral blood mononuclear cell (PBMC) and relevant Axl signaling and 
inhibition biomarker analysis will be performed at Screening, Cycle 1 Day 4 and 8 and every 
study visit thereafter until Cycle 9 Day 1. 
Blood sampling for bemcentinib pharmacokinetic analysis will be performed on blood samples 
taken pre-dose on: 
•
Cycle 1, Days 1 and 3 as follows: pre-dose and at 2, 4, 6 and 8 hours post dose;
•
Cycle 1, pre-dose on Days 2, 4, 8 and 15;
•
Cycles 2 and 3, pre-dose (study days 22 and 43 respectively).
Blood sampling for pembrolizumab pharmacokinetic analysis will be performed on blood 
samples taken pre-dose on Cycle 1, Days 1 to 4, 8 and 15 and then pre-dose at Cycles 2 and 3 
(study days 22 and 43 respectively). These samples will be frozen and stored centrally for 
future reference and analysis. 
Patients with tumor amenable to repeat sampling may have additional fresh biopsies taken on 
up to 2 occasions post-dose at time points agreed between the Investigator and the Sponsor. 
Where possible, efforts will be made to obtain follow up biopsy material where a patient has 
responded to treatment or has progressed on treatment. 
Further details on sample collection and handling for all PK and biomarker assessments are 
described in the Laboratory Manual. 
Patients who discontinue bemcentinib treatment (for reasons other than disease progression) 
may be able to continue with (monotherapy) pembrolizumab until 106 weeks (that is, 35 
completed cycles of pembrolizumab). These patients will no longer be required to have the 
following assessments from 6 weeks after the discontinuation of bemcentinib (unless clinically 
indicated): 
•
ECG;
•
Echocardiogram (or Multi Gated Acquisition Scan (MUGA));
•
Optional tumor biopsy (for example at subsequent progression);
•
Biomarker sampling.
The Post Treatment Visit will occur 30 days after the patient has discontinued both treatments 
on study. Patients who withdraw from either or both study treatments prior to disease 
progression will continue to have tumor assessment scans on study every 12 weeks until 
disease progression is documented (and confirmed, if necessary). The date of disease 
progression will be captured.  
Patients will continue to have their survival status checked every 12 weeks until either the 
patient dies or the study ends. Telephone contact is acceptable. 
Inclusion/Exclusion Criteria: 
Inclusion Criteria 
A patient will be suitable to proceed to treatment on study if they meet all of the following 
criteria: 
 
Provision of signed informed consent. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
12 of 126 
Male and non-pregnant females who are aged 18 years or older at the time of 
provision of informed consent. 
Histopathologically or cytologically documented Stage IV adenocarcinoma 
non-small cell lung cancer (NSCLC). Note: Patients with a mixed histology 
including a significant area of adenocarcinoma histology are eligible.  
Cohort A: Has disease progression on or after a prior platinum-containing 
chemotherapy. Note: Patients with Epidermal growth factor receptor (EGFR) 
mutations or ALK genomic rearrangements must have documented disease 
progression on at least one licensed therapy for these indications and may not have 
received platinum-containing chemotherapy. 
Cohort B: a) Has received a maximum of one prior line of an anti-PD-(L)1 therapy 
(monotherapy).   
b) Must have had disease control containing at least 2 doses of an anti-PD-(L)1
therapy. Disease control is defined as:
i.
Stable disease (SD) for at least 12 weeks (date of first progression on
anti-PD-(L)1 therapy)
Or
ii.
Confirmed 
partial 
response 
or 
complete 
response
(PR/CR): confirmatory scan must be performed >4 weeks from initial
scan
c) Has disease progression when entering screening (first date of progression of
disease is taken as the end date of response to previous anti-PD-(L)1 therapy) and
this must be within 12 weeks of last dose of treatment containing an anti-PD-(L)1
therapy. Progression should have been confirmed in one of the following ways:
i.
Having had two scan assessments completed at least 4 weeks apart, both
showing progression according to RECIST 1.12 or
ii.
Having had one scan assessment completed showing disease
progression according to standards used for previous therapy combined
with rapid disease progression / clinical progression.
Cohort C: a) Has received a maximum of one prior line of an anti-PD-(L)1 therapy 
in combination with a platinum-containing chemotherapy. 
b) Must have had disease control containing at least 2 doses of anti-PD-(L)1
therapy. Disease control is defined as:
i.
Stable disease (SD) for at least 12 weeks (date of first progression on
anti-PD-(L)1 therapy)
Or
ii.
Confirmed partial response or complete response (PR/CR) must be
confirmed - confirmatory scan must be performed >4 weeks from initial
scan
c) Has disease progression when entering screening (first date of progression of
disease is taken as the end date of response to previous anti-PD-(L)1 therapy) and
this must be within 12 weeks of last dose of treatment containing an anti-PD-(L)1
therapy. Progression should have been confirmed in one of the following ways:
i.
Having had two scan assessments completed at least 4 weeks apart, both
showing progression according to RECIST 1.12 or
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
13 of 126 
ii.
Having had one scan assessment completed showing disease
progression according to standards used for previous therapy combined
with rapid disease progression / clinical progression.
Measurable disease as defined by RECIST 1.12 on computed tomography (CT) or 
magnetic resonance imaging (MRI) and as determined by the site study team. 
Tumor lesions situated in a previously irradiated area are considered measurable if 
progression has been demonstrated in such lesions. 
Provision of suitable tumor tissue for the analysis of Axl kinase expression and 
PD-L1 expression. Suitable tumor tissue must consist of a minimum of newly 
acquired (fresh) tumor tissue sample (as a FFPE block), together with either further 
newly acquired tumor tissue (i.e., further FFPE block) or an archival tumor tissue 
sample (as a further FFPE block or further 10 unstained slides). See Section 5.3.13 
for further details. 
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 
[Appendix A]. 
Life expectancy of at least 3 months. 
Adequate organ function confirmed at Screening within 10 days of treatment 
initiation - as evidenced by: 
a.
Platelet count ≥100,000 /mm3;
b.
Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L);
c.
Absolute neutrophil count (ANC) >1,500 /mm3;
d.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5
times the upper limit of normal (ULN), or ≤5 times the ULN for patients
with liver metastases;
e.
Total bilirubin ≤1.5 times the ULN;
f.
Creatinine ≤1.5 times the ULN or calculated creatinine clearance 60 mL/min
(by Cockcroft Gault formula; see Appendix B);
g.
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times
the ULN and Activated Partial Thromboplastin Time (aPTT) ≤1.5 times the
ULN. Note: If patient is receiving anticoagulant therapy, then PT or Partial
thromboplastin time (PTT) must be within therapeutic range of intended use
of anticoagulants.
Female patients of childbearing potential 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.  
Patients (both male and female) of reproductive potential must be willing to 
practice highly effective methods of contraception (such as those described 
in Section 6.14) throughout the study and for 120 days after the last dose of 
study medication. Abstinence is acceptable if this is the usual lifestyle for the 
patient. Female patients are considered NOT of childbearing potential if they have 
a history of surgical sterility or evidence of post-menopausal status defined as 
any of the following: 
a.
≥45 years of age and has not had menses for more than 1 year;
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
14 of 126 
b.
Amenorrheic for >2 years without a hysterectomy and oophorectomy and a
follicle stimulating hormone (FSH) value in the postmenopausal range upon
Screening evaluation;
c.
Post hysterectomy, oophorectomy or tubal ligation. Documented
hysterectomy or oophorectomy must be confirmed with medical records of
the actual procedure or confirmed by an ultrasound. Tubal ligation must be
confirmed with medical records of the actual procedure.
Have resolution of toxic effect(s) of the most recent prior cancer therapy to Grade 1 
or less (except alopecia). If the patient received major surgery or radiation therapy 
of > 30 Gy, they must have recovered from the toxicity and/or complications from 
the intervention. 
Exclusion Criteria 
A patient will not be suitable to proceed to treatment on study if they meet any of the following 
criteria: 
1.
Has disease suitable for local therapy administered with curative intent.
2.
Has received more than one prior line of chemotherapy for advanced or metastatic
adenocarcinoma of the lung.
For all cohorts: Note: Patients may have received additional prior radiotherapy or
chemotherapy in the adjuvant setting, providing it was completed at least 6 months
prior to start of study treatment.
3.
Cohort A: Has received prior therapy with an immunomodulatory agent; Cohort
B: Has received prior chemotherapy alone or in combination with immunotherapy
in the metastatic setting
4.
Has a known additional malignancy that is progressing or requires active treatment.
Note: Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy or in situ
cervical cancer.
5.
Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Patients with previously treated brain metastases may
participate provided they are stable (without evidence of progression by scans
(using the identical modality for each assessment, either MRI or CT scan) for at
least 4 weeks prior to the first dose of trial treatment and any neurological
symptoms have returned to baseline), have no evidence of new or enlarging brain
metastases, and are not using steroids for at least 7 days prior to trial treatment.
6.
History of the following cardiac conditions:
a.
Congestive cardiac failure of >Grade II severity according to the
NYHA (Appendix C: defined as symptomatic at less than ordinary levels of
activity).
b.
Ischemic cardiac event including myocardial infarction within 3 months
prior to first dose.
c.
Uncontrolled cardiac disease, including unstable angina, uncontrolled
hypertension (i.e., sustained systolic BP >160 mmHg or diastolic BP
>90 mmHg), or need to change medication due to lack of disease control
within 6 weeks prior to the provision of consent.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
15 of 126 
d.
History or presence of sustained bradycardia (≤55 BPM), left bundle branch
block, cardiac pacemaker, or ventricular arrhythmia. Note: Patients with a
supraventricular arrhythmia requiring medical treatment, but with a normal
ventricular rate are eligible.
e.
Family history of long QTc syndrome; personal history of long QTc
syndrome or previous drug-induced QTc prolongation of at least Grade 3
(QTc >500ms).
7.
Abnormal left ventricular ejection fraction on echocardiography or MUGA (less
than the lower limit of normal for a patient of that age at the treating institution or
<45%, whichever is lower).
8.
Current treatment with any agent known to cause Torsades de Pointes which
cannot be discontinued at least five half-lives or two weeks prior to the first dose
of study treatment.
9.
Screening 12-lead ECG with a measurable QTc interval according to Fridericia’s
correction >450 ms.
10.
Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of study treatment.
11.
Has participated in a study involving any immune checkpoint inhibitor other than
currently approved immune checkpoint inhibitors for their lung cancer.
12.
Received chemotherapy or targeted small molecule therapy or radiation therapy
within 2 weeks prior to starting study treatment or who has not recovered (i.e.,
≤Grade 1 at baseline) from AEs due to a previously administered agent. Note:
Patients with ≤Grade 2 alopecia are an exception to this criterion. If the patient
received major surgery, they must have recovered adequately from the toxicity
and/or complications from the intervention prior to starting therapy.
13.
Received an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the
first dose of study treatment or who has not recovered (i.e., ≤Grade 1 or baseline)
from AEs due to agents administered more than 4 weeks earlier.
14.
Major surgery within 28 days prior to start of study treatment and failure to have
recovered adequately from the toxicity and/or complications from the intervention
prior to the first dose of study treatment. Note: Major surgery does not include
procedures for insertion of venous catheters or biopsies.
15.
Received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including Granulocyte-colony
stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor
(GM-CSF) or recombinant erythropoietin) within 4 weeks prior to the first dose of
study treatment. Note: Patients receiving stable dose of growth factors with a
hemoglobin value that meets Inclusion Criterion 9b may be included.
16.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior to the first dose
of study treatment. Note: The use of physiologic doses of corticosteroids may be
approved after consultation with the Sponsor
17.
Active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
16 of 126 
drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is 
not considered a form of systemic treatment. 
18.
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
19.
Has known active infection with Hepatitis B (e.g., HBsAg reactive) or Hepatitis C
(e.g., HCV Ribonucleic acid (RNA) [qualitative] is detected). Note: i) Patients with
a history of hepatitis B infection are eligible provided they are hepatitis B surface
antigen negative ii) Patients with a history of hepatitis C infection are eligible
provided they have no evidence of hepatitis C RNA using a qPCR at least 6 months
after completing treatment for hepatitis C infection.
20.
Has received a live-virus vaccination within 30 days of planned treatment start.
Note: Seasonal flu vaccines that do not contain live virus are permitted.
21.
Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
22.
Has a history of interstitial lung disease.
23.
Inability to swallow or tolerate oral medication.
24.
Existing gastrointestinal disease affecting drug absorption such as celiac disease or
Crohn’s disease, or previous bowel resection which is considered to be clinically
significant or could interfere with absorption.
25.
Known lactose intolerance.
26.
Requires vitamin K antagonists. Note: Patients receiving low doses prescribed to
maintain the patency of venous access devices may be included. Note: Factor Xa
antagonists are permitted.
27.
Treatment with any of the following: histamine receptor 2 inhibitors, proton pump
inhibitors or antacids within 7 days of start of study treatment.
28.
Treatment with any medication which is predominantly metabolized by CYP3A4
and has a narrow therapeutic index.
29.
Known severe hypersensitivity (≥Grade 3) to bemcentinib, pembrolizumab, and/or
any of their excipients.
30.
Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac
conditions, or ongoing.
31.
Has active infection requiring systemic therapy (apart from cutaneous infections).
32.
Has received radiation to the lung of >30 Gy within 6 months of first dose.
33.
Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the patient’s
participation for the full duration of the trial, or means it is not in the best interest
of the patient to participate, in the opinion of the Investigator.
34.
Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting from Screening through to 120 days after
the last dose of study treatment.
35.
Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
36.
Cohorts B and C: Has an EGFR mutation or ALK genomic rearrangement.
37.
Has received an allogeneic tissue/solid organ transplant.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
17 of 126 
Statistical Methods and Sample Size 
Evaluable for safety (ES): An evaluable patient will have received at least one combination 
dose. 
Evaluable for efficacy (EE): An evaluable for safety (ES) patient who has at least one 
on -treatment scan as per protocol schedule. 
Cohort A will follow a k-stage single arm design with k=2, being a Simon’s 2-stage design1. 
In this design with k=2, there are two analyses: an interim (Stage 1) analysis for DRC review 
and a final (Stage 2; once all patients have been treated and/or followed up for at least 24 
months) analysis. At the interim analysis, the response rate is evaluated in a fixed number (m) 
of patients using a predefined decision rule to determine if the study should stop for futility (in 
the situation where the null is confirmed). If the null hypothesis is not confirmed, a further 
fixed number of patients (l) are assessed for response and a final analysis is performed on all 
(m+l) patients. In both interim and final analyses, the response rate will be presented together 
with the associated exact 90% confidence interval (CI). 
The rationale for a null hypothesis of p0=0.15 is based on previously published analysis from 
495 patients with NSCLC (Keynote 001), who received at least one dose of pembrolizumab, 
where an ORR of 19.4% (95% CI 16.0-23.2) was observed for pembrolizumab monotherapy. 
The median duration of response was 12.5 months. Of these 495 patients, 394 patients were 
previously treated and likely to be a similar patient population to that being considered for this 
study. An ORR of 18.0% (95% CI 14.4 to 22.2) was observed in these previously treated 
patients. 
The ORR of pembrolizumab in combination with bemcentinib is expected to be at least as high 
as this in an unselected patient population, and considerably higher in patients with positive 
(≥1%) PD-L1 expression. 
With p0=0.15 and p1=0.30, the interim (Stage 1) analysis will be conducted with m=22 
evaluable for efficacy patients (EE). If 3 or fewer responses are observed in up to 22 patients, 
the cohort will be terminated in favor of the null for futility. Otherwise, up to a further 26 
patients may be evaluated, for a maximum total of 48 evaluable patients. If a total of 12 or 
more responses are seen in up to 48 evaluable patients (25%), then the null will have been 
rejected in favor of the alternative; otherwise, the null will not have been rejected. 
Up to 48 evaluable patients may therefore be enrolled to cohort A. It is expected that 
approximately 64 patients will be screened in order to identify 48 evaluable patients who meet 
all the inclusion and exclusion criteria and who are evaluable for response in cohort A. 
Cohort B will follow a k-stage single arm design with k=2, being a Simon’s 2-stage design as 
above.  
The rationale for a null hypothesis of p0=0.05 is based on historic response rates to standard 
second and later line single agent chemotherapy such as docetaxel. In a phase III trial enrolling 
patients who had previously failed platinum-containing chemotherapy, 373 patients received 
either 100 mg/m2 or 75 mg/m2 docetaxel. An ORR of 10.8 and 6.7%, respectively, was 
observed in these patients3.   
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
18 of 126 
The ORR of pembrolizumab in combination with bemcentinib is expected to be at least as high 
as this in patients who progressed on first- or second line immune checkpoint inhibitor therapy. 
With p0=0.05 and p1=0.20, the interim (Stage 1) analysis will be conducted with m=13 
evaluable for efficacy patients (EE). If 1 confirmed response is observed after the 13th patient 
has been followed-up for 24 weeks, a subgroup of the DRC will meet to confirm continuation 
to Stage 2. If 0 responses are observed in up to 13 patients, the cohort will be terminated in 
favor of the null for futility. Otherwise, up to a further 16 patients may be evaluated (in Stage 
2), for a maximum total of 29 (EE) evaluable patients. Once 16 (EE) evaluable patients have 
been enrolled in Stage 2, an interim analysis (Stage 2; once all patients have been treated and/or 
followed up for at least 12 months) and a final analysis (at the time of study completion – see 
Section 8.6 for details) will be performed. If a total of 4 or more responses (either at Stage 2 
interim analysis or at final analysis) are seen in up to 29 evaluable patients (13.8%), then the 
null will have been rejected in favor of the alternative; otherwise, the null will not have been 
rejected. 
Up to 29 evaluable patients may therefore be enrolled to cohort B. It is expected that 
approximately 36 patients will be screened in order to identify 29 patients who meet all the 
inclusion and exclusion criteria and who are evaluable for response in cohort B. 
Demographic and clinical characteristics at entry will be summarized using appropriate 
descriptive statistics. PD-L1 and Axl expression will be summarized for the ES. 
Cohort C will be similar to cohort B in terms of size and design. It will follow a k-stage single 
arm design with k=2, being a Simon’s 2-stage design as above.  
The rationale for a null hypothesis of p0=0.05 is based on historic response rates to standard 
second line single agent chemotherapy such as docetaxel. In a phase III trial enrolling patients 
who had previously failed platinum-containing chemotherapy, 373 patients received either 
100 mg/m2 or 75 mg/m2 docetaxel. An ORR of 10.8 and 6.7%, respectively, was observed in 
these patients4.   
The ORR of pembrolizumab in combination with bemcentinib is expected to be at least as high 
as this in patients who progressed on first- or second line immune checkpoint inhibitor therapy. 
With p0=0.05 and p1=0.20, the interim (Stage 1) analysis will be conducted with m =13 
evaluable for efficacy patients (EE). If 1 confirmed response is observed after the 13th patient 
has been followed up for at least 24 weeks a subgroup of the DRC will meet to confirm 
continuation to Stage 2. If 0 responses are observed in up to 13 patients, the cohort will be 
terminated in favor of the null for futility. Otherwise, up to a further 16 patients may be 
evaluated, for a maximum total of 29 evaluable patients. Once 16 (EE) evaluable patients have 
been enrolled in Stage 2, an interim analysis (Stage 2; once all patients have been treated and/or 
followed up for at least 12 months) and a final analysis (at the time of study completion – see 
Section 8.6 for details) will be performed. If a total of 4 or more responses (either at Stage 
 interim analysis or at final analysis) are seen in up to 29 evaluable patients (13.8%), then 
 
null will have been rejected in favor of the alternative; otherwise, the null will not have been 
rejected. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
19 of 126 
Up to 29 evaluable patients may therefore be enrolled to cohort C. It is expected that 
approximately 36 patients will be screened in order to identify 29 patients who meet all the 
inclusion and exclusion criteria and who are evaluable for response in cohort C. 
Demographic and clinical characteristics at entry will be summarized using appropriate 
descriptive statistics. PD-L1 and Axl expression will be summarized for the ES. 
Further details on the statistical methods and sample size can be found in Section 8. 
Schedules of Assessment and Pembrolizumab Administration Timing 
Table 3 summarizes the timing of pembrolizumab administration up to Cycle 35 
(approximately 24 months of treatment) in relation to the timing of disease assessment. 
Table 4 summarizes the schedule of assessments in Year 1 and Table 5 summarizes the 
schedule of assessments in Year 2. 
Table 6 summarizes the schedule of assessments after 35 cycles. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Table 3: Pembrolizumab 3 Weekly Schedule and Disease Assessment Timings 
Year 1, First 6 months* 
\Veek: 
1 
4 
7 
10 
13 
16 
19 
22 
25 
Start of month: 
1 
4 
7 
Pembrolizumab cycle: 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Disease Assessment/ Scan 
screening 
X 
X 
(+/- 7 days): 
Year 1, Second 6 months* 
\Veek: 
28 
31 
34 
37 
40 
43 
46 
49 
52 
Start of month: 
10 
13 
Pembrolizumab cycle: 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Disease Assessment I Scan 
X 
X 
X 
(+/- 7 days): 
Year 2, First 6 months* 
\Veek: 
55 
58 
61 
64 
67 
70 
73 
76 
79 
Start of month: 
16 
19 
Pembrolizumab cycle: 
19 
20 
21 
22 
23 
24 
25 
26 
27 
Disease Assessment I Scan 
X 
X 
(+/- 7 days): 
Year 2, Second 6 months* 
\Veek: 
82 
85 
88 
91 
94 
97 
100 
103 
106 
Start of month: 
22 
25 
Pembrolizumab cycle: 
28 
29 
30 
31 
32 
33 
34 
35 
Stop** 
Disease Assessment I Scan 
X 
X 
X 
(+/- 7 days): 
* A month ts 4 weeks (not a calendar month). 
**Participants who are still on study treatment after 3 5 cycles and have not experienced radiological progression may continue 
to receive study treatment under the BGBC008 protocol upon approval by the Sponsor, if the investigator believes that 
continuation of study treatment is in the best interest of the patient. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
20 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Table 4: Schedule of Study Assessments - Year 1 
Day 
.$(-re,e.ai:a.g 
C,·d• I (!1-d •rd•) 
! 
Upto-28 
1 
2 
3 • 
3 
15 
22 
 
36 
Start ofWe-ek#(+/-
-4 Wffks to 
I 
! 
3 
4 
5 
6 
3 .i.,;) 
0 
Demograpllit-s" 
X 
Medic-al history 
X 
ladwion/ exdusioo 
X 
,he<ks 
Pngna<· or FSH 
X 
X 
tut' 
ECOCPS 
X 
X 
Vital sip,2 
X 
X 
X 
X 
X 
X 
X 
X 
Ph)'$ical 
X 
X 
X 
X 
X 
X 
X 
X 
e.u.miu..atioo3 
CJ.ioiul c-hemistr)Ja 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hem.atologr11 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation.-
X 
X 
X 
X 
X 
Uriasis 
X 
X 
X 
X 
X 
Thyroid fuac-tioa 
X 
tut 
[d1oc-ardiog:ram (or 
X 
MUCA)" 
ECC' 
X 
.:K 
X 
X 
X 
X 
X 
X 
Tum.or as$eSSllleot 
X 
sc-a.as' 
Disuise assessmeot1 
X 
BGBC008 I PN-531 -NSCLC Version l 1.0 
C cont.,...t1a1 
Cyde Num.b,e.r - Year 1 
3 
4 
5 
6 
7 
8 
9 
10 
'3 
se 
57 .. 1' 
1' 
1' 
1' 
1" 
1" 
7 
8 
9 
10 
13 
16 
19 
l! 
?5 
!8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
26 January 2022 
11 
I! 
L! 
14 
15 
1• 
1" 
1" 
1" 
1" 
31 
34 
37 
40 
43 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
21 of 126 
16 
1" 
46 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Post T rutmeat 
17 
,isit'" 
FoUow 
Upl.5 
1• 
+30 from last 
d ... 
49 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(X) 
(X) 
(X) 
(X) 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Tumor (fresh tissue) 
X 
biop,,-' 
Tumor (atthfral)" 
(X) 
Biom.arbrs" 
X 
(X) 
X 
X 
Pembrolizumab 
X 
dosing'• 
BCB3l4 dosiag11 
PK sampling 
S 
X S X 
X 
(BCB3!4)" 
PK sampling 
X 
X X 
X 
X 
(pembrolizumab)11 
. .\dnr.seneats 
X 
X X 
X 
X 
Co...-om.itaat 
X 
X 
X X 
X 
X 
m.edk-atioa 
Subsequent anti-
Ulk'er tnatmeot 
Sunival follow up15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BGBC008 I PN-531 - NSCLC Version 11.0 
C Col'lfidential 
X 
X 
(X: up to 2 optimw post tre-biopsws) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-couseculin d.ily dosing iD 21 d cyoles 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
26 Janua1y 2022 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
22 of 126 
X 
X 
X 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
X 
X 
X 
X 
X 
(X) 
(X) 
X 
X 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Table 5: Schedule of Study Assessments - Year 2 
Cycle Number - Year 2 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
Day 
1u 
I 13 
I 13 
1u 
I 13 
113 
I 13 
I 13 
I 13 
I 13 
I 13 
I 13 
I 13 
Week Number(+/- 3 days) 
52 
55 
58 
61 
64 
67 70 
73 
76 
79 
82 
85 88 
Pregnancy test1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOGPS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical chemistryn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology18 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation• 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
Thyroid function tests5 
X 
X 
X 
X 
X 
X 
Echoca1'diog1·am (or i\lUGA)16 
X 
ECG' 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor assessment scans' 
X 
X 
X 
Disease Assessment' 
X 
X 
X 
Tumor (fresh tissue) biopsy8 
(X: up to 2 optiooal post treatment biopsies) 
Pembrolizumab dosing19 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bemcentinib dosing 11 
X -consecutive daily dosing in 21-<I cycles 
Adnrse ennts 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subsequent anti-cncer treatment 
Survival Follow Up15 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 Janua1y 2022 
C Col'lfidential 
31 
32 
33 
34 
35 
I 13 
1u 
1u 
I 13 
I 13 
91 
94 
97 
100 103 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
23 of 126 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Post 
Treatment 
Visitu 
Follow 
Upl5 
+30ftom
last dose 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(X) 
(X) 
(X) 
(X) 
X 
(X) 
X 
(X) 
X 
X 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Table 6: Schedule of Study Assessments-After 35 Cycles 
Cycle Number 
CN1t 
Post Treatment 
FollowUp15 
Visit1' 
Day 
113 
+30 from last dose 
Week Number(+/- 3 days) 
WNW 
Pregnancy test1 
X 
ECOGPS 
X 
X 
Vital signs2 
X 
X 
Physical examination3 
X 
X 
Clinical c.hemiSh·y18 
X 
X 
Hematology18 
X 
X 
Coagulation• 
X 
Urinalysis 
X 
Thy1·oid func.tion tests• 
x21 
X 
Echocardiogram (or J\IUGA)16 
-
-
ECG6 
X 
X 
Tnmor assessment scans' 
X 
X 
XIS
Disease Assessment' 
X 
X 
x•• 
Tnmor (fresh tissne) biopsy• 
X 
Bemcentinib dosing 11
X 
Adnrse ennts 
X 
X 
Concomitant medication 
X 
X 
Subsequent anti-cncer treatment 
X 
Survival Follow Up15 
X 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 Janua1y 2022 
C Col'lfidential 
24 of 126 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
General instt·uclions: 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Informed Consent must be obtained using the current version of the PIS/I CF prior to commencing Screening. Re-consenting of patients is permitted on approval by the Sponsor 
• 
From C 2  onwards a tolerance window of +/-3 days is permitted. Other tolerance windows for specific study assessments are described in the footnotes below. 
• 
On dosing days, assessments should be performed prior to dosing unless specified otherwise. 
• 
(X) denotes an optional sample or a sample which is not taken at every cycle;Ĩ denotes a study visit with multiple samples. Please refer to Footnotes. 
Additional assessments may be carried out at any point in the study where clinically indicated. 
Footnotes: 
A pregnancy test is required within 3 days prior to CID!. A negative pregnancy test may be confirmed by urine or blood test. Where a urine test is positive or equivocal, a 
blood test must be performed to confirm the result. Patients requiring confirmation of post-menopausal status will have FSH levels assessed at Screening. Where applicable, 
and in accordance with local regulations, a pregnancy test should be conducted at each cycle (or monthly). 
2 
Vital signs will include temperature, systolic blood pressure, diastolic blood pressure, heart rate and respiratory rate. On pembrolizumab dosing days, vital signs will be taken 
both pre-<lose and at the end of infusion. 
3 
Physical examination includes height at Screening and weight at Screening and the start of each cycle. After Screening, further assessments may be symptom-directed. 
4 
Coagulation parameters may be assessed from the Hematology sample. 
5 
Thyroid function testing may be assessed from the Clinical chemistry sample. 
6 
For each ECG assessment, triplicate 12-lead ECGs must be taken less than 5 minutes apart, with the patient having rested for at least JO minutes in the supine position prior 
to assessment. Time points are relative to bemcentinib dosing: C l  DI pre-<lose and 6 hours post dose; D2 pre-<lose; D3 pre-<lose; D4 pre-dose. Samples should be 
contemporaneously with bemcentinib PK blood sampling time-points. All other time-points are pre-dose unless clinically indicated. If a patient has bemcentinib interrupted 
for 14 days for QTc prolongation or 12 weeks for immune-related toxicities, an ECG will be conducted twice weekly for the following 2 weeks once a patient restarts daily 
dosing. If a patient permanently discontinues bemcentinib (but continues pembrolizumab ), the last ECG will be performed at the next pembrolizumab administration. 
7 
Tumor assessment scans will be performed at Screening, then every 9 weeks for the first 46 weeks, and then every 12 weeks thereafter(+/- 7 days). 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 assessment scans schedule should be maintained by week number. The schedule of disease assessments is every 12 weeks once a patient has stopped (one or both 
study treatments) or completed their treatment in the absence of progression. These may continue into Follow Up. 
8 
Fresh tumor tissue taken within 3 months of first dose (provided the patient has not received any further chemotherapy or immunotherapy, or other anti-cancer therapy in the 
intervening period and that sufficient tumor tissue is available) from all patients at Screening is mandatory, and optional at up to 2 time points during participation in the 
clinical trial ('on-study' biopsy). Where possible, these optional samples should be taken at the point of tumor response or progression. Suitable archival biopsy material may 
also be obtained at Screening. Please refer to protocol Section 5. 3 .13, the Laboratory or Pathology Manual for full details on biopsy sample collection, time-points, processing, 
storage and shipment. Jfa patient discontinues bemcentinib (but continues pembrolizumab), there is no requirement for the optional 'on study' biopsy. 
9 
Blood samples will be collected at Screening (or DI pre-<lose), D4, D8, then at every study visit up to and including C9 DI to prepare PBMC and serum samples for relevant 
Axt signaling and inhibition biomarker assessment. Please refer to the Laboratory Manual for full details on biomarker sample collection, time-points, processing, storage 
and shipment. 
10 
Pembrolizumab dose of200 mg will be administered every 3 weeks (timing window +/- 3 days). Each dose will be infused over 30 minutes (timing window -5/+ 10 minutes) 
11 
Bemcentinib will be taken orally once daily. On visits when pembrolizumab and bemcentinib are given on the same day, pembrolizumab must be given first and the patient 
observed for I h prior to administration ofbemcentinib. 
12 
a) The maximum PK sampling time points for the measurement ofbemcentinib in blood will be: CJ DI pre-dose, 2, 4, 6, 8 hours; D2 pre-dose; D3 pre-dose, 2, 4, 6, 8 hours; 
D4 pre-<lose; and then pre-<lose at CID8, CID15, C2Dl and then C3Dl . Samples should be taken contemporaneously with the ECG assessments on CJ Dl-4. All sample 
times are approximate, but every effort must be made to take PK samples at specified times. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 Janua1y 2022 
25 of 126 
C Col'lfidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
b) The maximum PK sampling time points for the measurement of pembrolizumab in blood will be: C l  DI pre-dose; D2; D3; D4; and then at CID8, CIDJ5, C2DI 
pre-pembro dose and then C3DI pre-pembro dose. All sample times are approximate but every effort must be made to take PK samples at specified times 
c) All sample times are approximate and every effort must be made to take PK samples at specified times. Actual sampling times must be recorded in order to assess result 
relative to bemcentinib or pembrolizumab dose. Please refer to the local Laboratory Manual for full details on PK sample collection, time-points, processing, storage 
and shipment. 
13 
DI of next cycle would be "D22" of the previous cycle. 
14 
A Post Treatment Visit is to be conducted up to 30 days (+/-3 days) from last dose of study drug. AEs and concomitant medications must be assessed to 30 days. Some
AEs must be assessed for longer (see Section 7.4.3 and Section 7.5). Other assessments may be carried out between 7-30 days from last dose. Tumor assessment scans and 
disease assessment is only required when part of next scheduled disease assessment is (where patient has not yet progressed) or to confirm response or progression. 
15 
Tumor assessment scans and disease assessment will continue every 12 weeks from last dose of study drug where patient has not yet progressed or to confirm response 
or progression. An assessment of disease status, survival status and details of any anti-cancer therapies received after last dose of study drug will also be collected. 
Survival status can be collected by telephone. 
16 
Echocardiogram (or MUGA) will be conducted every 6 months whilst a patient receives bemcentinib. If a patient discontinues bemcentinib (but continues pembrolizumab ), 
a final echocardiogram (or MUGA) will be conducted only if one is scheduled in the following 6 weeks. 
17 
Demography- race, ethnicity, gender, age (birth month and year). 
18 
Hematology and Clinical Chemistry to be assessed at a suitable time prior to administration of study treatment(s). 
19 
Participants who are still on study treatment after 35 cycles and have not experienced radiological progression may continue to receive bemcentinib under the BGBC008 
protocol upon approval by the Sponsor, if the investigator believes that continuation of study treatment is in the best interest of the patient 
20 
Treatment visits after every 3 weeks (or 21 days)
21 
Thyroid function test performed at every other cycle 
BGBC008 I PN-531 - NSCLC Version 11.0 
C Col'lfidential 
26 Janua1y 2022 
26 of 126 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
02 December 2021 
27 of 126 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ..............................................................................................................5 
1 
INTRODUCTION............................................................................................................37 
1.1 
Non-Small Cell Lung Cancer ........................................................................................37 
1.2 
Rationale for Study BGBC008 ......................................................................................37 
1.3 
Non-Clinical Studies with Bemcentinib ........................................................................39 
1.3.1 
Non-Clinical Pharmacology of Bemcentinib .........................................................39 
1.3.2 
Non-clinical toxicology of Bemcentinib ................................................................40 
1.3.3 
Pharmacokinetics and Metabolism of Bemcentinib ..............................................41 
1.4 
Clinical Studies with Bemcentinib ................................................................................41 
1.4.1 
Safety Summary and Reference Safety Information .............................................42 
1.5 
Rationale for Bemcentinib Dose and Schedule Selection .............................................42 
1.6 
Pembrolizumab Background and Clinical Trials ..........................................................44 
1.6.1 
Rationale for pembrolizumab dose selection .........................................................44 
2 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................46 
3 
SELECTION CRITERIA ...............................................................................................47 
3.1 
Inclusion Criteria ...........................................................................................................47 
3.2 
Exclusion Criteria ..........................................................................................................49 
3.3 
Patient Withdrawal of Consent and Discontinuation of Treatment ..............................52 
3.4 
Permitted Cessation of Pembrolizumab Treatment on Study .......................................53 
3.5 
Definition of Evaluable Patient, Acceptable Compliance, and Replacement of 
Patients ..........................................................................................................................53 
3.6 
Procedures for Patient Cessation of Study Treatment ...................................................53 
3.7 
Study or Site Termination .............................................................................................53 
4 
STUDY DESIGN ..............................................................................................................55 
4.1 
Cohort A - Safety Run-In ..............................................................................................57 
4.2 
End of Stage 1 – Efficacy Analysis and Review of Emerging Risk-Benefit 
Profile ............................................................................................................................57 
4.3 
Duration of Treatment ...................................................................................................60 
5 
STUDY SCHEDULE .......................................................................................................61 
5.1 
Schedule of Study Assessments ....................................................................................61 
5.1.1 
Schedule of Study Assessments – Year 1, Year 2 and beyond Cycle 35 ..............61 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           28 of 126 
5.2 
Volume of Blood Sampling ...........................................................................................65 
5.3 
Description of Study Interventions and Assessments ...................................................66 
5.3.1 
Demography and medical history ..........................................................................66 
5.3.2 
Pregnancy and FSH test .........................................................................................66 
5.3.3 
ECOG performance score ......................................................................................66 
5.3.4 
Vital signs ..............................................................................................................66 
5.3.5 
Physical exam ........................................................................................................67 
5.3.6 
Clinical chemistry, hematology, coagulation and urinalysis .................................67 
5.3.7 
Thyroid function test ..............................................................................................67 
5.3.8 
Echocardiography or MUGA .................................................................................68 
5.3.9 
Electrocardiogram ..................................................................................................68 
5.3.10 
Tumor Assessment Scans ......................................................................................69 
5.3.11 
Disease assessment ................................................................................................69 
5.3.12 
Biomarkers .............................................................................................................70 
5.3.13 
Tumor Sample Requirements ................................................................................70 
5.3.14 
Pharmacokinetics ...................................................................................................71 
6 
STUDY MEDICATION AND ADMINISTRATION ...................................................72 
6.1 
Preparation and Dosing of Study Treatments ................................................................72 
6.1.1 
Bemcentinib ...........................................................................................................72 
6.1.2 
Pembrolizumab ......................................................................................................72 
6.2 
Treatment Compliance ..................................................................................................72 
6.3 
Storage of Study Treatments .........................................................................................73 
6.3.1 
Bemcentinib ...........................................................................................................73 
6.3.2 
Pembrolizumab ......................................................................................................73 
6.4 
Drug Accountability ......................................................................................................73 
6.5 
Method of Enrolling Patient to Study Treatment ..........................................................74 
6.6 
Dose Modifications .......................................................................................................74 
6.6.1 
Bemcentinib dose modification for toxicity ..........................................................74 
6.6.2 
Pembrolizumab dose modifications .......................................................................78 
6.6.3 
Dose modifications for bemcentinib and pembrolizumab for overlapping 
toxicities .................................................................................................................83 
6.6.3.1 
Dose modifications for diarrhea .....................................................................83 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           29 of 126 
6.6.3.2 
Dose modifications for rash (including dermatitis, pruritus) – Table 
15 ....................................................................................................................84 
6.6.3.3 
Dose modifications for renal toxicity (renal failure, serum 
creatinine elevation, nephritis) – Table 16 .....................................................84 
6.6.3.4 
Dose modifications for Increased AST and/or ALT with or without 
increased bilirubin – Table 17 ........................................................................85 
6.7 
Blinding and Procedures for Un-blinding the Study .....................................................85 
6.8 
Permitted and Restricted Concomitant Medications .....................................................86 
6.9 
Acceptable Concomitant Medications ...........................................................................86 
6.10 
Prohibited Concomitant Medications whilst receiving Pembrolizumab .......................86 
6.11 
Supportive Care Guidelines and Rescue Medications for Pembrolizumab ..................87 
6.12 
Infusion Guidelines for Pembrolizumab .......................................................................87 
6.13 
Diet, Activity and Other Considerations .......................................................................89 
6.13.1 
Diet .........................................................................................................................89 
6.14 
Contraception ................................................................................................................89 
6.14.1 
Use in pregnancy....................................................................................................91 
6.14.2 
Use in nursing women ...........................................................................................91 
7 
ADVERSE EVENTS AND REPORTING REQUIREMENTS ...................................92 
7.1 
Assessment of Safety .....................................................................................................92 
7.2 
Adverse Event Definition ..............................................................................................92 
7.3 
Importance of Adverse Event Reporting .......................................................................93 
7.4 
Evaluating Adverse Events ...........................................................................................94 
7.4.1 
Assessment of severity ...........................................................................................94 
7.4.2 
Assessment of relationship ....................................................................................94 
7.4.3 
Immediate reporting of AEs and events of clinical interest to the Sponsor...........95 
7.4.3.1 
Serious adverse events ....................................................................................95 
7.4.3.2 
Events of clinical interest ................................................................................96 
7.4.4 
Reporting SAEs and ECIs ......................................................................................97 
7.4.5 
Assessment of Expected Adverse Events ..............................................................98 
7.5 
Reporting of Pregnancy or Lactation ............................................................................98 
7.6 
Definition of Misuse and Overdose ...............................................................................98 
7.7 
Investigational Product Complaints ..............................................................................98 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           30 of 126 
7.8 
Reporting SAEs to the IRB or IEC ...............................................................................99 
7.9 
Follow Up Information on an SAE ...............................................................................99 
7.10 
Sponsor Reporting of SAEs ..........................................................................................99 
7.10.1 
Expedited reporting ..............................................................................................100 
7.10.2 
Non-expedited reporting ......................................................................................100 
8 
DATA EVALUATION: CRITERIA FOR EVALUATION OF OBJECTIVES .....101 
8.1 
Statistical Considerations, Interim Analysis and Sample Size ....................................101 
8.2 
Data Review Committee .............................................................................................102 
8.2.1 
Cohort A - Safety Run-In .....................................................................................102 
8.2.2 
Cohort A - End of Stage 1 – Efficacy Analysis ...................................................102 
8.2.3 
Cohort B – End of Stage 1 – Efficacy Analysis...................................................103 
8.2.4 
Cohort C – End of Stage 1 – Efficacy Analysis...................................................103 
8.3 
Statistical Analysis Plan ..............................................................................................103 
8.4 
Population ....................................................................................................................104 
8.5 
RECIST 1.1 and Disease Assessment .........................................................................104 
8.5.1 
Immune-related RECIST and confirmation of progression .................................106 
8.6 
Completion and Closure of the Study .........................................................................107 
8.7 
Demographic, Medical History, Prior Medication and Other Baseline 
Characteristics .............................................................................................................108 
8.8 
Study Treatment ..........................................................................................................108 
8.9 
Concomitant Medication .............................................................................................108 
8.10 
Reasons for Discontinuation from Study Treatment ...................................................108 
8.11 
Primary Objective ........................................................................................................108 
8.12 
Secondary Objectives ..................................................................................................109 
8.12.1 
Safety ...................................................................................................................109 
8.12.1.1 Adverse events ..............................................................................................109 
8.12.1.2 Safety laboratory ...........................................................................................110 
8.12.1.3 Vital signs .....................................................................................................110 
8.12.1.4 Electrocardiogram .........................................................................................110 
8.12.2 
Efficacy ................................................................................................................110 
8.12.2.1 Duration of response .....................................................................................110 
8.12.2.2 Disease control rate .......................................................................................110 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           31 of 126 
8.12.2.3 Progression free survival and overall survival ..............................................110 
8.12.3 
Pharmacokinetics .................................................................................................111 
8.13 
Exploratory Objectives ................................................................................................111 
8.13.1 
Biomarker analysis...............................................................................................111 
9 
QUALITY ASSURANCE .............................................................................................112 
9.1 
Data Recording ............................................................................................................112 
9.2 
Study Monitoring ........................................................................................................112 
9.3 
Clinical Study Audit ....................................................................................................112 
9.4 
Clinical Study Report ..................................................................................................112 
9.5 
Data Retention and Availability ..................................................................................112 
9.6 
Curricula Vitae and Financial Disclosure of Investigators .........................................113 
9.7 
Protocol Modifications ................................................................................................113 
10 
ETHICS REVIEW/INFORMED CONSENT AND COMPETENT 
REGULATORY AUTHORITY APPROVAL ............................................................114 
10.1 
Ethical Conduct of the Study .......................................................................................114 
10.2 
Institutional Review Board or Independent Ethics Committee and Competent 
Regulatory Authority Approvals .................................................................................114 
10.3 
Informed Consent ........................................................................................................114 
10.4 
Patient Participation Card ............................................................................................116 
10.5 
Insurance .....................................................................................................................116 
10.6 
Patient Privacy .............................................................................................................116 
11 
PUBLICATION POLICY .............................................................................................117 
12 
APPENDIX A: EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS .........................................................................................118 
13 
APPENDIX B: CREATININE CLEARANCE ALGORITHM ................................119 
14 
APPENDIX C: THE NEW YORK HEART ASSOCIATION (NYHA) 
FUNCTIONAL CLASSIFICATION IN A PATIENT WITH HEART 
DISEASE ........................................................................................................................120 
15 
APPENDIX D: DRUGS ASSOCIATED WITH TORSADES DE POINTES ..........121 
16 
APPENDIX E: LOCAL LABORATORY PARAMETERS ......................................123 
17 
REFERENCES ...............................................................................................................124 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           32 of 126 
List of Tables 
Table 1: Study Objectives and Endpoint (Assessment) ...................................................................5 
Table 2: Bemcentinib and Pembrolizumab Dosing .........................................................................8 
Table 3: Pembrolizumab 3 Weekly Schedule and Disease Assessment Timings .........................20 
Table 4: Schedule of Study Assessments - Year 1 ........................................................................21 
Table 5: Schedule of Study Assessments - Year 2 ........................................................................23 
Table 6: Schedule of Study Assessments- After 35 Cycles ...........................................................24 
Table 7: Bemcentinib Kinase Selectivity Profile ...........................................................................39 
Table 8: Preliminary PK Data from Bemcentinib Studies in Patients ...........................................44 
Table 9: Bemcentinib and Pembrolizumab Dosing .......................................................................57 
Table 10: Product Descriptions ......................................................................................................72 
Table 11: Dose Modification of Bemcentinib for Toxicity ...........................................................74 
Table 12: Dose Modification of Bemcentinib for QTc Prolongation ............................................75 
Table 13: Dose Modification and Toxicity Management Guidelines for Immune-related AEs 
Associated with Pembrolizumab ..............................................................................79 
Table 14: Pembrolizumab and Bemcentinib Dose Modification for Diarrhea ..............................83 
Table 15: Pembrolizumab and Bemcentinib Dose Modifications for Rash ..................................84 
Table 16: Pembrolizumab and Bemcentinib Dose Modification for Renal Toxicity ....................84 
Table 17: Pembrolizumab and Bemcentinib Dose Modifications for Increased AST and/or 
ALT With or Without Increased Bilirubin ...............................................................85 
Table 18: Management of Pembrolizumab-associated Infusion-related Reactions .......................88 
Table 19: Contact Details for SAE, ECI, New Cancer and Pregnancy/Lactation Reporting ........97 
Table 20: RECIST 1.1 Evaluation and Definitions of Disease Response ...................................105 
Table 21: Overall Visit Response Algorithm...............................................................................106 
Table 22: Pharmacokinetic Parameters ........................................................................................111 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           33 of 126 
List of Figures 
Figure 1: Schematic Diagram of the Study Design .........................................................................7 
Figure 2: Bemcentinib in Combination with PD-1 and PD-L1 Inhibitors .....................................40 
Figure 3: Simulated Plasma Concentrations of Bemcentinib Following Repeat Once Daily 
Oral Administration of 
 Bemcentinib to Healthy Male Subjects Under 
Fasted Conditions (Loading Dose of 
 on Day 1 and Day 2) ........................43 
Figure 4: Study Flow Chart............................................................................................................59 
Figure 5: Dose Modification of Bemcentinib for Increased ALT/AST With or Without 
Increased Bilirubin ...................................................................................................77 
Figure 6: Sample Patient Participation Card ................................................................................116 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           34 of 126 
LIST OF ABBREVIATIONS 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
ANC 
Absolute neutrophil count 
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under the curve 
AUC0-∞ 
AUC from time zero to infinity 
AUC0-24h 
AUC from time zero to 24 hours 
AUC0-48h 
AUC from time zero to 48 hours 
BP 
Blood pressure 
BPM 
Beats per minute 
Cav 
Average concentration 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum concentration achieved 
CNS 
Central nervous system 
CR 
Complete response 
CRF 
Case report form 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CrCl 
Creatinine Clearance 
CV 
Cardiovascular 
DCR 
Disease control rate 
DILI 
Drug-Induced liver Injury 
DRC 
Data Review Committee 
DoR 
Duration of response 
DRESS 
Drug Reaction with Eosinophilia and Systemic Symptoms 
DSUR 
Development Safety Update Report 
EC 
European Community 
EC 
Ethics committee 
ECG 
Electrocardiogram 
ECI 
Events of clinical interest 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EE 
Evaluable for efficacy 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           35 of 126 
EGFR 
Epidermal growth factor receptor 
EMT 
Epithelial-to-mesenchymal transition 
ES 
Evaluable for safety 
EU 
European Union 
FDA 
Food and Drug Administration 
FPI 
First patient in 
FPPE 
Formalin fixed paraffin embedded 
FSH 
Follicle-stimulating hormone 
FT3 
Free Triidothyromine 
GCP 
Good Clinical Practice 
G-CSF
Granulocyte-colony stimulating factor 
GM-CSF 
Granulocyte-macrophage colony-stimulating factor 
GMP 
Good Manufacturing Practice 
HCV 
Hepatitis C virus 
hERG 
Human ether-à-go-go related gene 
HIV 
Human immunodeficiency virus 
HPMC 
Hydroxypropyl methylcellulose 
Hr 
Hour 
i.v.
Intravenous(ly) 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
IEC 
Institutional Ethics Committee 
IHC 
Immunohistochemistry 
IMP 
Investigational medicinal product 
irAE 
Immune-related adverse event 
IND 
Investigational new drug 
INN 
International Nonproprietary Name 
INR 
International normalized ratio 
irAE 
Immune-related adverse event 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
LL 
Lewis Lung 
LPLV 
Last patient, last visit 
mAb 
Monoclonal antibody 
MDS 
Myelodysplastic syndrome 
mOS 
Median Overall Survival 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
MUGA 
Multi Gated Acquisition Scan 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NYHA 
New York Heart Association 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           36 of 126 
ORR 
Objective Response Rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell(s) 
PD 
Pharmacodynamic(s) 
PFS 
Progression-free survival 
PIS 
Patient information sheet 
PK 
Pharmacokinetic 
PT 
Prothrombin time 
PTT 
Partial Thromboplastin Time 
Q2W 
(dose) every 2 weeks 
Q3W 
(dose) every 3 weeks 
QD 
(dose) daily 
qPCR 
Quantitative polymerase chain reaction 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval utilizing Fridericia’s correction 
RNA 
Ribonucleic acid 
RTK 
Receptor tyrosine kinases 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SJS 
Steven Johnson Syndrome 
SmPC 
Summary of Product Characteristics 
SUSAR 
Suspected unexpected serious adverse reaction 
TEN 
Toxic Epidermal Necrolysis 
t½ 
Elimination half-life 
T3 
Triiodothyromine 
TL 
Target lesion 
tmax 
Time to maximum concentration 
TMF 
Trial Master File 
TPS 
Tumor proportion score 
TSH 
Thyroid stimulating hormone 
ULN 
Upper limit of normal 
US 
United States (of America) 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           37 of 126 
1 
INTRODUCTION 
This is an open-label, Phase II, Simon 2-stage design1 study of the anti-tumor activity and safety 
of bemcentinib, an Axl kinase inhibitor, when given in combination with pembrolizumab, the 
humanized monoclonal antibody (mAb) which targets the programmed death receptor-1 (PD-1) 
protein in patients with previously treated, advanced adenocarcinoma of the lung (cohort A).  
Cohort B will assess the anti-tumor activity and safety of bemcentinib when given in combination 
with pembrolizumab in patients with advanced adenocarcinoma of the lung who have been 
previously treated with any anti-PD-(L)1 therapy.  Twenty-nine evaluable patients will be enrolled. 
Cohort C will assess the anti-tumor activity and safety of bemcentinib when given in combination 
with pembrolizumab in patients with advanced adenocarcinoma of the lung who have been 
previously treated with any anti-PD-(L)1 therapy in combination with a platinum-containing 
chemotherapy. 29 evaluable patients will be enrolled. 
1.1 
Non-Small Cell Lung Cancer 
Lung cancer has been the most common cancer worldwide for several decades. It is estimated that 
there were 1.8 million new cases of lung cancer in 2012 (13.0% of total incidence). Lung cancer 
is also the leading cause of cancer death worldwide (19.4%), with only 15% of patients alive 
5 years after diagnosis5. Non-small cell lung cancer (NSCLC) accounts for 85 to 90% of lung 
cancers6. 
Surgery is the preferred treatment approach for NSCLC patients with early-stage disease, although 
over 60 to 65% of patients present with Stage IIIb/IV disease, which is unsuitable for resection. 
Chemotherapy with a platinum-based doublet is standard of care for patients with advanced 
NSCLC. Patients with Stage IV disease typically die from their disease, with overall median 
survival of 8 to 10 months and only 33% of these patients are still alive 1 year from diagnosis7. 
Docetaxel and pemetrexed are used as second-line chemotherapy offering an improvement in 
median and 1-year survivals compared with best supportive care. Specific targeted therapies have 
been developed for the treatment of advanced NSCLC including the vascular endothelial growth 
factor inhibitor bevacizumab and the EGFR inhibitors erlotinib, gefitinib and cetuximab. The 
immunotherapies nivolumab and pembrolizumab, that target the programmed cell death receptor 
PD-1, represent an alternative therapy in patients following progression after first line 
chemotherapy. In patients with NSCLC, there is a progressive decline in response to repeated lines 
of therapy, primarily due to development of biologic resistance within the underlying tumor and a 
progressive decline in patient performance status (PS) resulting from treatment-related and 
disease-related morbidities (National Comprehensive Cancer Network Treatment Guidelines 
Version 4, 2014). 
1.2 
Rationale for Study BGBC008 
Bemcentinib is a potent selective small molecule inhibitor of Axl, a surface membrane protein 
kinase receptor that is over-expressed in many metastatic solid tumors and has been identified as 
a marker of a poor prognosis in patients with NSCLC. 
Axl is a member of the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (RTKs) that 
regulate multiple cellular processes. These include cell survival, proliferation, and migration. Mer 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           38 of 126 
and Axl share the natural ligand Gas6, which binds Axl with 3-10 fold greater intensity than Mer8. 
The role of these RTKs in normal physiology appears related to clearance of apoptotic cells, 
cytokine secretion, platelet aggregation, erythropoiesis, and natural killer cell differentiation and 
maturation9,10,11,12. The oncogenic potential of Axl has been attributed to autocrine and paracrine 
functions. In addition to signaling through canonical PI3K/Akt and MAPK/Erk pathways, Axl may 
also mediate tumor-stromal cell interactions, resulting in modification of the inflammatory 
response and angiogenesis13,14. Recently, Axl has also been implicated in epithelial-to-
mesenchymal transition (EMT), which promotes metastasis and giving cells the ability to migrate 
through extracellular matrix and intravasate into blood vessels15. 
In NSCLC, Axl expression is associated with poor clinical outcomes, lymph node involvement, 
and higher disease stage16. Axl and Gas6 ligand have been detected at high levels in more than 
50% of NSCLC cell lines17. Further suggesting a major role in NSCLC biology, Axl is also among 
the most highly phosphorylated (i.e., activated) receptor tyrosine kinases (RTKs) in NSCLC cell 
lines and tumors18,19.  
It has been reported that Axl mediates resistance to immunotherapy and chemotherapy in a variety 
of cancer types, including NSCLC20, breast cancer21 and esophageal adenocarcinoma22. EMT is a 
common mechanism of resistance to chemotherapy, including resistance to docetaxel. Axl 
activation causes EMT23, while inhibition of Axl can reverse mesenchymal phenotype, thereby 
restoring drug sensitivity. 
Pembrolizumab [Keytruda (US)], a humanized monoclonal antibody against the programmed 
death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of patients 
with cancer. Pembrolizumab is approved for treatment of patients with melanoma in several 
countries; in the US and EU it is approved for the treatment of patients with advanced (unresectable 
or metastatic) melanoma in adults. Pembrolizumab has also been approved for treatment of 
patients with NSCLC in several countries; in the US it is indicated for the treatment of patients 
with metastatic NSCLC whose tumors express PD-L1 using a tumor proportion score (TPS) of 
50% or greater, and as determined by an FDA-approved test and who have disease progression on 
or after platinum-containing chemotherapy. Patients with NSCLC driven by EGFR mutations or 
ALK genomic rearrangements should also have disease progression on FDA-approved therapy for 
these molecular targets prior to receiving pembrolizumab. 
As described above, EMT is the process consisting of multiple biochemical changes by which 
polarized epithelial cells gain a mesenchymal cell phenotype, leading to increased migration and 
invasive properties. In cancer, EMT is a hallmark of invading cells and consequently cancer / 
metastases. It is increasingly understood that cancers are recognized by the immune system and, 
under some circumstances, the immune system may control or even eliminate tumors24. However, 
if elimination is incomplete, the tumor may evolve mechanisms to avoid or attenuate the immune 
system. In the tumor microenvironment, PD-L1 expressed on tumor cells binds with PD-1 on 
activated T-cells reaching the tumor. This delivers an inhibitory signal to those T-cells, preventing 
them from killing the tumor cells, and thus, protecting the tumor from immune elimination25.  
A strong association between EMT status and an inflammatory tumor micro-environment with 
elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD1, PD-L2, 
BTLA, CTLA-4 etc. has been shown26. Multiple agents, including pembrolizumab, that target 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
these checkpoint molecules, are in development for a range of cancers that are considered to have 
highly immunogenic microenvironments. More recently, the increasing role of immtme checkpoint 
blockade has led to rapidly growing interest in resistance mechanisms to these agents and, perhaps 
expectedly given Axl's role in immune evasion, emerging data show that increased Axl expression 
is a component of an anti-PD-I resistance program in non-responders27.
Bemcentinib has been shown to potentiate the effect of PD-1/PD-Ll inhibition and to enhance 
tumor leukocyte infiltration in a lung cancer syngeneic model in C57Bl /6 mice (Section 1.3 and 
the bemcentinib Investigator's Brochure [IB]). There is, therefore, a strong scientific rationale for 
combination of bemcentinib with pembrolizumab in advanced NSCLC cancer. The proposed 
population will have advanced disease and therefore, the combination of bemcentinib with 
pembrolizumab is expected to increase the response rate and prolong the duration of response. 
1.3 
Non-Clinical Studies with Bemcentinib 
Please refer to the cunent version of the bemcentinib Investigator's Brochure for fiuther details of 
the non-clinical studies with bemcentinib. 
1.3.1 
Non-Clinical Pharmacology of Bemcentinib 
Bemcentinib demonstrates potent inhibition of Axl in biochemical and cell-based kinase inhibition 
assays. The selectivity ofbemcentinib for Axl is illustrated in Table 7. 
Table 7: Bemcentinib Kinase Selectivity Profile 
KinomeScan 
Kinase Profile!' 
BaF3 cell-based kinase 
activity assay 
Kinase 
binding assay 
kinase activity assay 
(ICS4) 
(Kd) 
(IC54) 
nM 
Fold 
nM 
Fold 
nM 
fold 
Ax1 
0.4 
1 
4.6 
1 
63 
1 
Tie2 
270 
680 
30 
6.4 
355 
5.5 
Ret 
73 
180 
38 
8.1 
>316 
>5 
Fltl 
400 
>1000 
40 
8.7 
>1000 
>15 
Flt4 
460 
>1000 
41 
8.8 
>1000 
>15 
Yes 
810 
>1000 
43 
9.2 
n/a 
n/a 
n/a = not applicable 
Bemcentinib inhibits the growth and smvival of hunor cell lines derived from a range of solid and 
leukemic tumors. 
In the syngeneic Lewis Ltmg (LL/2) ltmg carcinoma model, bemcentinib significantly potentiated 
the effect of anti-mPD-l+anti-mPD-Ll antibody treatment and reduced hunor growth and 
enhanced smvival compared to anti-mPD-l+anti-mPD-Ll treatment alone. Anti-mPD-l+anti­
mPD-Ll treatment induced EMT in the syngeneic LL/2 model. This induction of AxlAXL, 
vimentin, N-cadherin and PD-Ll was prevented by treatment with bemcentinib. Bemcentinib 
BGBC008/ PN-531 - NSCLC Version 11.0 
26 Janua1y 2022 
39 of 126 
C
confldent&al 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
treatment enhanced hllllor infiltration of cytotoxic T-lymphocytes, NK and NKT cells and reduced 
the number of anti-hllllorigenic mMDSC. 
Bemcentinib in combination with PD-I and PD-LI inhibitors significantly reduces hllllor vohlllle 
at Day 21 and prevents (tumor) upregulation of PD-LI, in syngeneic lung carcinoma model 
(Figure 2): 
Figure 2: Bemcentinib in Combination with PD-1 and PD-Ll Inhibitors 
-
200 
nE .s. 1SO 
Tumor Volumes day 12 
e 
.• 
:i 100 
 
•• 
li so 
E  
I-
1.3.2 
Non-clinical toxicology ofBemcentinib 
PD-L1 
To suppo1t clinical studies with bemcentinib a series of animal toxicology and safety studies, 
including 28-day repeat dosing sh1dies in rodents and monkeys and a single dose telemetered 
cardiovascular (CV) safety sh1dy in monkeys, have been conducted. Comparisons of the data 
reported in the rodent and monkey studies indicate that primates are more sensitive to bemcentinib 
on a per body weight basis. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
40 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
1.3.3 
Pharmacokinetics and Metabolism ofBemcentinib 
1.4 
Clinical Studies with Bemcentinib 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Please refer to the cmTent version of the bemcentinib Investigator's Brochure for ftuther details of 
the clinical studies with bemcentinib. 
A phase I, first-in-human study in healthy male subjects (Study BGBC00l) has been completed. 
Four clinical studies are cmTently active with BerGenBio ASA as the Sponsor (BGBC003, 
BGBC004, BGBC007 and BGBC008) with a ftuther two investigator led clinical studies and 
enrolling patients with advanced cancers. Bemcentinib is being evaluated as single agent as well 
as in combination with other anti-cancer therapies. Study BGBC003 will explore bemcentinib 
given as monotherapy and in combination with standard treatments in patients with AML/MDS. 
Study BGBC004 will explore bemcentinib in combination with erlotinib in patients with NSCLC. 
Study BGBC007 and BGBC008 assess the antitumor activity and safety of bemcentinib in 
combination with pembrolizumab in patients with previously treated, locally advanced and 
unresectable, metastatic lNBC or TN-IBC and previously treated, advanced adenocarcinoma of 
the lung respectively. 
BGBC008 I PN-53 l - NSCLC Version 11.0 
26 January 2022 
41 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Additional infonnation from investigator led studies can be found in Section 5.1 (Ove1view of 
Clinical Studies) of the Investigator's Brochure. 
1.4.1 
Safety Summary and Reference Safety Information 
The reference safety info1mation is based on a cut-off date of 30 July 2019 (consistent with 1B 
v.13.0) for ongoing clinical studies BGBC003, BGBC004, BGBC007, and BGBC008. For
investigator-led studies BGBIL005 and BGBIL006 only exposure and SAE data are included up
to the cut-off date of 30 July 2019. Please refer to the latest edition of the 1B for the most up-to­
date safety info1mation during the conduct of this clinical study.
1.5 
Rationale for Bemcentinib Dose and Schedule Selection 
To date, the bemcentinib clinical program has utilized two different fo1mulations. Formulation 1, 
consisting ofbemcentinib API, was used in the healthy volunteer study (Study BGBC00l) and the 
first study of bemcentinib in patients (Study BGBC003 in patients with AML). From Study 
BGBC004 onwards, a blended fo1mulation including standard excipients, known as Fo1mulation 
2 has been used. 
Daily dosing with - bemcentinib has been perfo1med in patients with NSCLC and 
relapsed/refracto1y AML. Serial specimens of myeloid blasts have been collected from patients 
with AML. Paired biopsies have not been taken from patients with NSCLC. In myeloid blasts 
samples collected from patients who have completed 21-days of therapy exhibit reduced levels of 
phospho-Axl, phospho-Akt and phospho-ERK. All of these changes are consistent with inhibition 
of intracellular signaling pathways which are driven by signaling through Axl. Fmther evidence 
of Axl modulation in patients treated at this dose level is evident in the accompanying increase in 
soluble Axl which is closely related to the average concentration achieved. Increased levels of 
soluble Axl occurs downstream of increased sheddase activity following inhibition of intracellular 
MAPK signaling. These observations suggest that a daily dose of - bemcentinib has 
significant impact on inllibiting Axl signaling in patients. 
In Study BGBC00l, 32 subjects received doses ofbemcentinib in the range 
under 
fasted conditions, of which seven also received the same dose ofbemcentinib under fed conditions. 
The tmax and the apparent te1minal elimination t½ were generally comparable between fed and 
fasted conditions; tmax ranged fro© and t½ ranged from 
(except in 
one subject where t½ was reliably estimated as-). There was an increase in systeinic 
exposure to bemcentinib in three subjects, no appreciable change in three subjects and an apparent 
reduction in systeinic exposure in one subject when bemcentinib was given with food compared 
to under fasted conditions. 
Overall, Cmax and AUCo-48h under fed conditions were 
greater, respectively 
compared to fasted conditions; however, the 95% CI of the ratio (fed/fasted) included 100%, 
indicating that the apparent effect of food was not statistically significant. The elimination of 
BGBC008 I PN-53 l - NSCLC Version 11.0 
26 January 2022 
42 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           43 of 126 
bemcentinib was slow with a t½ of longer than 24 hours. A consequence of this prolonged t½ is the 
delay in the time taken to achieve steady state, which is estimated to be approximately two weeks 
following the initiation of BGB324 administration. Such a delay would not be therapeutically 
acceptable in patients with advanced cancers. 
The proposed starting dose and dosing schedule for clinical studies of bemcentinib in patients was 
therefore based on a one-compartment model, incorporated a lag time and no weighting to 
available clinical pharmacokinetic (PK) data. According to this model it was anticipated that the 
application of a loading dose (on Days 1, 2 and 3) would enable a rapid achievement of therapeutic 
levels of bemcentinib, and subsequent maintenance daily dosing would maintain optimum 
exposures whilst preventing wide changes in systemic concentration during therapy. The simulated 
mean plasma concentration-time profile of bemcentinib following a loading dose of 
 on 
Day 1 and Day 2 and 
 daily thereafter as a maintenance dose is presented in Figure 3. 
Figure 3: Simulated Plasma Concentrations of Bemcentinib Following Repeat Once Daily 
Oral Administration of 
 Bemcentinib to Healthy Male Subjects Under 
Fasted Conditions (Loading Dose of 600 mg on Day 1 and Day 2) 
This dose and scheduling regimen for the administration for bemcentinib using Formulation 1 is 
expected to achieve steady state concentrations of bemcentinib within one week of starting 
therapy. The geometric mean PK parameters of bemcentinib (administered as Formulation 1) 
derived from clinical studies BGBC003 and BGBC004 are compared and summarized in Table 8. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Table 8: Preliminary PK Data from Bemcentinib Studies in Patients 
Study Numbe1· 
AUC0-?4b 
c .. 
Cau 
(Daily Dose mg)/ 
CV 
CV 
Numbei- of patients 
(ng.h/mL) 
(%)* 
(ng/mL) 
(%)* 
(ng/mL) 
BGBC003 IIII 
2584 
82.0 
108 
82.0 
109 
BGBC003 .. 
2978 
100 
124 
100 
132 
BGBC004 .. 
6423 
57.3 
268 
57.3 
310 
BGBC003111 
10431 
73.4 
435 
73.4 
441 
*CV= Coefficient of Variation 
CV 
(% )* 
81.4 
97. 
45.8 
80.4 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
t½ 
(h) 
CV(%) 
141 
57.4 
107 
135 
82.9 
83.1 
180 
176 
Systemic exposure from Fo1mulation 1 in Study BGBC003 is markedly lower than that from 
Fo1mulation 2 in Sh1dy BGBC004. Fmthermore, systemic exposure from Formulation 1 is lower 
than that from F 01mulation 2 in Sh1dy BGBC003. Between-patient variability in systemic exposure 
to bemcentinib appeared to be lower after administration of Fo1mulation 2 (in shldy BGBC004) 
compared to Fo1mulation 1. The lower variability may be associated with enhanced solubility of 
bemcentinib in Fo1mulation 2, a fo1mulated product with solubilisers and particle size 
considerations. This will enable a product with a dissolution profile suitable for oral administration 
intended for immediate release in the stomach in the fasted state. The difference in systemic 
exposure between the two formulations could also have occtmed as a result of administering 
bemcentinib in the fed or fasted state. For Study BGBC008 the sta1ting dose will be 400 mg loading 
dose on Days 1, 2 and 3, followed by a daily maintenance dose of 200 mg. Bemcentinib will be 
administered on an empty stomach, at approximately the same time each day; antacids are not used 
for at least 2 hours after intake ofbemcentinib (see IB for details). 
1.6 
Pembrolizumab Background and Clinical Trials 
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) 
with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its 
interaction with programmed cell death ligand 1 (PD-Ll) and programmed cell death ligand 2 
(PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor 
blocking activity for PD-1. Pembrolizumab has an acceptable preclinical safety profile and is in 
clinical development as an intravenous (IV) immunotherapy for advanced malignancies. 
Keytmda TM (pembrolizumab) is indicated for the treatment of patients across a number of 
indications. For more details on specific indications refer to the Investigator's brochure (IB). 
1.6.1 
Rationale for pembrolizumab dose selection 
The planned dose ofpembrolizumab for this study is 200 mg every 3 weeks (Q3W). Based on the 
totality of data generated in the Keytmda development program, 200 mg Q3W is the appropriate 
dose of pembrolizumab for adults across all indications. As outlined below, this dose is justified 
by: 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
44 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           45 of 126 
•
Clinical data from 8 randomized studies in melanoma and NSCLC indications
demonstrating flat dose- and exposure-efficacy relationships from 2 mg/kg Q3W to
10 mg/kg every 2 weeks (Q2W), representing an approximate 5 to 7.5-fold exposure range
(refer to the IB),
•
Population PK analysis showing that both fixed dosing and weight-based dosing provides
similar control of PK variability with considerable overlap in the distributions of exposures,
supporting suitability of 200 mg Q3W,
•
Clinical data showing meaningful improvement in benefit-risk including overall survival
at 200 mg Q3W across multiple indications, and
•
Pharmacology data showing full target saturation in both systemic circulation (inferred
from PK data) and tumor (inferred from physiologically based PK [PBPK] analysis) at 200
mg Q3W.
Among the 8 randomized dose-comparison studies, a total of 2262 participants were enrolled with 
melanoma and non-small cell lung cancer (NSCLC), covering different disease settings (treatment 
naïve, previously treated, PD-L1 enriched, and all-comers) and different treatment settings 
(monotherapy and in combination with chemotherapy). Five studies compared 2 mg/kg Q3W 
versus 10 mg/kg Q2W (KN001 Cohort B2, KN001 Cohort D, KN002, KN010, and KN021), and 
3 studies compared 10 mg/kg Q3W versus 10 mg/kg Q2W (KN001 Cohort B3, KN001 Cohort F2 
and KN006). All of these studies demonstrated flat dose- and exposure-response relationships 
across the doses studied representing an approximate 5- to 7.5-fold difference in exposure. The 
2 mg/kg (or 200 mg fixed-dose) Q3W provided similar responses to the highest doses studied. 
Subsequently, flat dose-exposure-response relationships were also observed in other tumor types 
including head and neck cancer, bladder cancer, gastric cancer and classical Hodgkin Lymphoma, 
confirming 200 mg Q3W as the appropriate dose independent of the tumor type. These findings 
are consistent with the mechanism of action of pembrolizumab, which acts by interaction with 
immune cells, and not via direct binding to cancer cells. 
Additionally, pharmacology data clearly show target saturation at 200 mg Q3W. First, PK data in 
KN001 evaluating target-mediated drug disposition (TMDD) conclusively demonstrated 
saturation of PD-1 in systemic circulation at doses much lower than 200 mg Q3W. Second, a PBPK 
analysis was conducted to predict tumor PD-1 saturation over a wide range of tumor penetration 
and PD-1 expression. This evaluation concluded that pembrolizumab at 200 mg Q3W achieves 
full PD-1 saturation in both blood and tumor. 
Finally, population PK analysis of pembrolizumab, which characterized the influence of body 
weight and other participant covariates on exposure, has shown that the fixed-dosing provides 
similar control of PK variability as weight-based dosing, with considerable overlap in the 
distribution of exposures from the 200 mg Q3W fixed dose and 2 mg/kg Q3W dose. Supported by 
these PK characteristics and given that fixed-dose has advantages of reduced dosing complexity 
and reduced potential of dosing errors, the 200 mg Q3W fixed-dose was selected for evaluation 
across all pembrolizumab protocols. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
2 
STUDY OBJECTIVES AND ENDPOINTS 
The objective of this study is to assess the anti-tumor activity of the combination treatment of 
bemcentinib and pembrolizumab in patients with previously treated, advanced adenocarcinoma of 
the lung. 
The study will emoll three coho1ts of patients with previously treated advanced adenocarcinoma 
of the lung: Cohort A will consist of patients who received a maximum of one prior line of 
platinum-containing chemotherapy and no prior immtmotherapy of any kind. Cohort B will consist 
of patients with a maximum of one prior line of an anti-PD-(L)l therapy (monotherapy). Coho1t 
C will consist of patients who received a maximum of one prior line of therapy with an anti-PD­
(L) 1 therapy in combination with a platinum-containing chemotherapy. 
I Objective
Primary: 
Endpoint (Assessment) 
•
To assess the anti-tumor activity ofbemcentinib and 
•
pembrolizwnab when given in combination.
Objective Response Rate (complete response and 
partial response). 
Secondary 
•
To 
assess 
the 
safety 
of bemcentinib 
and 
•
pembrolizwnab when given in combination.
The nwnber and frequency of adverse events; 
assessment of safety laboratory parameters, vital 
signs, and ECGs. 
•
To further assess the anti-tumor activity of the
combination ofbemcentinib and pembrolizumab.
•
To include Disease Control Rate, Duration of
Response, 
Progression-free 
Survival, 
median
Overall Survival, and 12-month Overall Survival.
•
To 
evaluate the pharmacokinetic profile
bemcentinib when given with pembrolizwnab.
Exploratory: 
•
To assess relevant biomarkers .
BGBC008 I PN-531 - NSCLC Version 11.0 
C
Confldentlal 
of • 
Assessment of pharmacokinetic variables including 
Cmu, AUC, and t½ 
•
To assess PD-Ll and Axl expression in patients 
with adenocarcinoma of the lung. 
•
To assess any correlation or association between
expression level of PD-Ll and Axl and anti-tumor
outcomes such as ORR.
•
Assessment of relevant biomarkers in tumor and
blood which support immune modulation and Axl
signaling.
•
Developing a radiomic signature as a response
prognostic biomarker.
26 January 2022 
46 of 126 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           47 of 126 
3 
SELECTION CRITERIA 
The study will enroll adult patients with pre-treated, advanced or metastatic adenocarcinoma of 
the lung. 
3.1 
Inclusion Criteria 
A patient will be suitable to proceed to treatment on study if they meet all of the following criteria: 
1.
Provision of signed informed consent.
2.
Male and non-pregnant females who are aged 18 years or older at the time of provision
of informed consent.
3.
Histopathologically or cytologically documented Stage IV adenocarcinoma NSCLC.
Note: Patients with a mixed cell histology including a significant area of
adenocarcinoma histology are eligible.
4.
Cohort A: Has disease progression on or after a prior platinum-containing
chemotherapy. Note: Patients with EGFR mutations or ALK genomic rearrangements
must have documented disease progression on at least one licensed therapy for these
indications and may not have received platinum-containing chemotherapy.
Cohort B: a) Has received a maximum of one prior line of an anti-PD-(L)1 therapy
(monotherapy).
b) Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy.
Disease control is defined as;
i.
Stable disease (SD) for at least 12 weeks (date of first progression on anti-
PD-(L)1 therapy)
Or
ii.
Confirmed partial response or complete response (PR/CR) - confirmatory
scan must be performed >4 weeks from initial scan)
c) Has disease progression when entering screening (first date of progression of disease
is taken as end date of response to previous anti-PD-(L)1 therapy) and this must be
within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy.
Progression should have been confirmed in one of the following ways:
i) Having had two scan assessments completed at least 4 weeks apart, both showing
progression according to RECIST 1.12 or
ii) Having had one scan assessment completed showing disease progression
according to standards used for previous therapy combined with rapid disease
progression / clinical progression.
Cohort C: a) Has received a maximum of one prior line of an anti-PD-(L)1 therapy in 
combination with a platinum-containing chemotherapy. 
b) Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy.
Disease control is defined as;
i.
Stable disease (SD) for at least 12 weeks (date of first progression on
anti-PD-(L)1 therapy)
Or
ii.
Confirmed partial response or complete response (PR/CR) - confirmatory
scan must be performed >4 weeks from initial scan
c) Has disease progression when entering screening (first date of progression of disease
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           48 of 126 
is taken as end date of response to previous anti-PD-(L)1 therapy) and this must be 
within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy. 
Progression should have been confirmed in one of the following ways: 
i.
Having had two scan assessments completed at least 4 weeks apart, both
showing progression according to RECIST 1.12 or
ii.
Having had one scan assessment completed showing disease progression
according to standards used for previous therapy combined with rapid
disease progression / clinical progression.
5.
Measurable disease as defined by RECIST 1.12 on computed tomography (CT) or
magnetic resonance imaging (MRI) and as determined by the site study team. Tumor
lesions situated in a previously irradiated area are considered measurable if progression 
has been demonstrated in such lesions.
6.
Provision of suitable tumor tissue for the analysis of Axl kinase expression and PD-L1
expression. Suitable tumor tissue must consist of a minimum of newly acquired (fresh)
tumor tissue sample (as a FFPE block), together with either further newly acquired
tumor tissue (i.e., further FFPE block) or an archival tumor tissue sample (as a further
FFPE block or further 10 unstained slides). See Section 5.3.13 in protocol for an
explanation.
7.
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 [Appendix
A].
8.
Life expectancy of at least 3 months.
9.
Adequate organ function confirmed at Screening within 10 days of treatment initiation
- as evidenced by:
a.
Platelet count ≥100,000 /mm3;
b.
Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L);
c.
Absolute neutrophil count (ANC) >1,500 /mm3;
d.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5
times the upper limit of normal (ULN), or ≤5 times the ULN for patients with
liver metastases;
e.
Total bilirubin ≤1.5 times the ULN, or direct bilirubin <ULN for patients with
total bilirubin levels >1.5 ULN.
f.
Creatinine ≤1.5 times the ULN or calculated creatinine clearance 60 mL/min (by
Cockcroft Gault formula; see Appendix B);
g.
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times the
ULN and Activated Partial Thromboplastin Time (aPTT) ≤1.5 times the ULN.
Note: If patient is receiving anticoagulant therapy, then PT or PTT must be
 
within therapeutic range of intended use of anticoagulants.
10.
Female patients of childbearing potential 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.
11.
Patients (both male and female) of reproductive potential must be willing to practice
highly effective methods of contraception (such as those described in Section 6.14)
throughout the study and for 120 days after the last dose of study medication.
Abstinence is acceptable if this is the usual lifestyle for the patient. Female patients
are considered NOT of childbearing potential if they have a history of surgical sterility
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           49 of 126 
or evidence of post-menopausal status defined as any of the following: 
a.
≥45 years of age and has not had menses for more than 1 year;
b.
Amenorrheic for <2 years without a hysterectomy and oophorectomy and a
follicle stimulating hormone (FSH) value in the postmenopausal range upon
Screening evaluation;
c.
Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy
or oophorectomy must be confirmed with medical records of the actual
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with
medical records of the actual procedure.
12.
Have resolution of toxic effect(s) of the most recent prior cancer therapy to Grade 1 or
less (except alopecia). If subject received major surgery or radiation therapy of
>30 Gy, they must have recovered from the toxicity and/or complications from the
intervention.
3.2 
Exclusion Criteria 
A patient will not be suitable to proceed to treatment on study if they meet any of the following 
criteria: 
1.
Has disease suitable for local therapy administered with curative intent.
2.
Has received more than one prior line of chemotherapy for advanced or metastatic
adenocarcinoma of the lung.
For all cohorts: Note: Patients may have received additional prior radiotherapy or
chemotherapy in the adjuvant setting, providing it was completed at least 6 months
prior to start of study treatment.
3.
Cohort A: Has received prior therapy with an immunomodulatory agent; Cohort B:
Has received prior chemotherapy alone or in combination with immunotherapy in the
metastatic setting
4.
Has a known additional malignancy that is progressing or requires active treatment.
Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma
of the skin that has undergone potentially curative therapy or in situ cervical cancer.
5.
Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by scans (using the identical
modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the
first dose of trial treatment and any neurological symptoms have returned to baseline),
have no evidence of new or enlarging brain metastases, and are not using steroids for
at least 7 days prior to trial treatment.
6.
History of the following cardiac conditions:
a.
Congestive cardiac failure of >Grade II severity according to the
NYHA (Appendix C: defined as symptomatic at less than ordinary levels of
activity).
b.
Ischemic cardiac event including myocardial infarction within 3 months prior to
first dose.
c.
Uncontrolled cardiac disease, including unstable angina, uncontrolled
hypertension (i.e., sustained systolic BP >160 mmHg or diastolic BP
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           50 of 126 
>90 mmHg), or need to change medication due to lack of disease control within
6 weeks prior to the provision of consent.
d.
History or presence of sustained bradycardia (≤55 BPM), left bundle branch
block, cardiac pacemaker, or ventricular arrhythmia. Note: Patients with a
supraventricular arrhythmia requiring medical treatment, but with a normal
ventricular rate are eligible.
e.
Family history of long QTc syndrome; personal history of long QTc syndrome
or previous drug-induced QTc prolongation of at least Grade 3 (QTc >500 ms).
7.
Abnormal left ventricular ejection fraction on echocardiography or Multi Gated
Acquisition Scan (MUGA) (less than the lower limit of normal for a patient of that age
at the treating institution or <45%, whichever is lower).
8.
Current treatment with any agent known to cause Torsades de Pointes which cannot
be discontinued at least five half-lives or two weeks prior to the first dose of study
treatment.
9.
Screening 12-lead ECG with a measurable QTc interval according to Fridericia’s
correction >450 ms.
10.
Is currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigational device
within 4 weeks of the first dose of study treatment.
11.
Has participated in a study involving any immune checkpoint inhibitor other than
currently approved immune checkpoint inhibitors for their lung cancer.
12.
Received chemotherapy or targeted small molecule therapy or radiation therapy within
2 weeks prior to starting study treatment or who has not recovered (i.e., ≤Grade 1 at
baseline) from adverse events due to a previously administered agent. Note: Patients
with ≤Grade 2 alopecia are an exception to this criterion.
If the patient received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
13.
Received an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first
dose of study treatment or who has not recovered (i.e., ≤Grade 1 or baseline) from
adverse events due to agents administered more than 4 weeks earlier.
14.
Major surgery within 28 days prior to start of study treatment and failure to have
recovered adequately from the toxicity and/or complications from the intervention
prior to the first dose of study treatment. Note: Major surgery does not include
procedures for insertion of venous catheters or biopsies.
15.
Received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including G-CSF, GM-CSF or
recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment.
Note: Patients receiving stable dose of growth factors with a haemoglobin value that
meets Inclusion Criterion 9b may be included.
16.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment. Note: The use of physiologic doses of corticosteroids may be approved after
consultation with the Sponsor.
17.
Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           51 of 126 
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a 
form of systemic treatment. 
18.
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
19.
Has known active infection with Hepatitis B (e.g., HBsAg reactive) or Hepatitis C
(e.g., HCV RNA [qualitative] is detected). Note: i) Patients with a history of hepatitis
B infection are eligible provided they are hepatitis B surface antigen negative ii)
Patients with a history of hepatitis C infection are eligible provided they have no
evidence of hepatitis C RNA using a qPCR at least 6 months after completing treatment
for hepatitis infection.
20.
Has received a live-virus vaccination within 30 days of planned treatment start. Note:
Seasonal flu vaccines that do not contain live virus are permitted.
21.
Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
22.
Has a history of interstitial lung disease.
23.
Inability to swallow or tolerate oral medication.
24.
Existing gastrointestinal disease affecting drug absorption such as celiac disease or
Crohn’s disease, or previous bowel resection which is considered to be clinically
significant or could interfere with absorption.
25.
Known lactose intolerance.
26.
Requires vitamin K antagonists. Note: Patients receiving low doses prescribed to
maintain the patency of venous access devices may be included. Note: Factor Xa
antagonists are permitted.
27.
Treatment with any of the following: histamine receptor 2 inhibitors, proton pump
inhibitors or antacids within 7 days of start of study.
28.
Treatment with any medication which is predominantly metabolized by CYP3A4 and
has a narrow therapeutic index.
29.
Known severe hypersensitivity (≥Grade 3) to bemcentinib, pembrolizumab, and/or any
of their excipients.
30.
Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac conditions,
or ongoing.
31.
Has active infection requiring systemic therapy (apart from cutaneous infections).
32.
Has received radiation to the lung of >30 Gy within 6 months of first dose.
33.
Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient’s participation for
the full duration of the trial, or means it is not in the best interest of the patient to
participate, in the opinion of the Investigator.
34.
Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting from Screening through to 120 days after the
last dose of study treatment.
35.
Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
36.
Cohorts B and C: Has an EGFR mutation or ALK genomic rearrangement.
37.
Has received an allogeneic tissue/solid organ transplant.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           52 of 126 
3.3 
Patient Withdrawal of Consent and Discontinuation of Treatment 
Patients may withdraw their consent to further treatment on study or withdraw their consent to any 
further participation in any further assessments at any time without stating a reason and without 
prejudice to further treatment. 
Patients who have withdrawn their consent to receive further treatment, but not withdrawn their 
consent to further participation in the study are expected to continue in follow-up to enable 
assessment of the duration of their response, stable disease or time to progression, and their 
survival status. 
Patients who discontinue bemcentinib treatment (for reasons other than disease progression) may 
be able to continue with (monotherapy) pembrolizumab until 106 weeks (that is, 35 completed 
cycles of pembrolizumab, equivalent to 24 calendar months).  
Patients who discontinue pembrolizumab (for reasons other than disease progression) may be able 
to continue with bemcentinib (monotherapy) upon approval by the Sponsor until Study Closure. 
A Post Treatment Visit should be performed 30 +/-3 days after the last dose of study treatment 
(bemcentinib and/or pembrolizumab), to enable follow up safety assessments and further tumor 
assessment where required.  
The Investigator may discontinue either or both the study treatments at any time. Example reasons 
for discontinuing a study treatment are: 
•
Patient withdrawal of consent to further treatment and/or further participation in the study.
•
Disease progression (although, treatment can continue if progression is suspected in the
absence of clinical deterioration – progression is to be confirmed no less than 4 weeks after
the initial observation).
•
The patient experiences a toxicity, considered related to bemcentinib, including those
necessitating a bemcentinib dose delay of 12 weeks (Section 6.6.1), where the
re-introduction of bemcentinib (including a dose reduction of bemcentinib), is not
considered suitable.
•
The patient experiences a toxicity, considered to be related to treatment with
pembrolizumab which necessitates pembrolizumab treatment withdrawal (Section 6.6.2).
•
Other toxicities or events, unrelated to bemcentinib or pembrolizumab, that would, in the
Investigator’s opinion, prevent the patient from continuing on study treatment(s).
•
Treatment non-compliance. (All documentation concerning the patient must be as
complete as possible). Withdrawals due to non-attendance of study visits must be
followed-up by the Investigator to obtain the reason for where possible. For further
information on treatment non-compliance, please see also Section 3.5).
•
Pregnancy.
A patient is defined as ‘lost to follow-up’ only if every effort has been made to contact the patient 
and determine the patient’s willingness to continue with all or some of the study assessments 
(irrespective of whether the patient is still receiving study treatment). 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           53 of 126 
Patients who are unwilling to continue to receive further treatment should be encouraged to 
continue to be follow-up to enable assessment of the duration of their response, stable disease or 
time to progression, and their survival status.  
The Sponsor reserves the right to request the withdrawal of study treatment from a patient due to 
protocol violation or other significant reason. 
3.4 
Permitted Cessation of Pembrolizumab Treatment on Study 
Note that Investigators may wish to stop pembrolizumab treatment per local treatment practice for 
patients who have attained a confirmed complete response (CR) that have been treated for at least 
24 months with pembrolizumab and had at least 2 treatments with pembrolizumab beyond the date 
when the initial CR was declared. Patients will remain on study and continue to receive 
bemcentinib treatment and continue disease assessments. 
Once pembrolizumab treatment has been stopped for this reason, it cannot be restarted on study. 
3.5 
Definition of Evaluable Patient, Acceptable Compliance, and Replacement of 
Patients 
Evaluable for safety (ES): An evaluable patient will have received at least one combination dose. 
Evaluable for efficacy (EE): An evaluable for safety patient who has at least one on-treatment 
scan per protocol schedule. 
Patients will be replaced if they are considered to be non-evaluable for efficacy. 
Patients who have failed screening (usually because they have failed one or more of the inclusion 
or exclusion criteria) will not receive study treatment and are not considered evaluable. 
Treatment non-compliance for this study will be defined as follows: 
•
For bemcentinib: missing more than 7 doses in any 21-day period (other than a dose delay
for toxicity management (Section 6.6.1)
•
For pembrolizumab: Dosing interruptions are permitted in the case of medical / surgical
events or logistical reasons not related to study therapy (for example, elective surgery,
unrelated medical events, patient vacation etc). Patients should be placed back on study
therapy within 3 weeks of the scheduled interruption. The reason for the interruption should
be documented in the patient’s study notes.
3.6 
Procedures for Patient Cessation of Study Treatment 
When a patient stops or discontinues one or both of their study treatments, the reason for cessation 
will be recorded in the patient file and the Case Report Form (CRF). Patients must complete a post 
treatment visit and continue with their scans and assessments of disease (if the patient has not 
already progressed) and/or survival status. 
3.7 
Study or Site Termination 
If the Sponsor or their representatives, Investigator, or Competent Authority officials discover 
conditions during the study that indicate that the study or site involvement should be terminated, 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           54 of 126 
this action may be taken after appropriate consultation with the Sponsor and the Investigator. 
Conditions that may warrant termination of the study or involvement of a study site include, but 
are not limited to: 
•
The discovery of an unexpected, serious, or unacceptable risk to patients enrolled in
the study.
•
The decision on the part of the Sponsor to suspend or discontinue testing, evaluation,
or development of the study drug.
•
Failure of the Investigator(s) to comply with pertinent clinical trial regulations.
•
Submission of knowingly false information from the research facility to the Sponsor,
study monitor, or Competent Authority.
•
Insufficient adherence to protocol requirements.
Study termination and follow-up will be performed in accordance with applicable local 
regulations. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           55 of 126 
 
4 
STUDY DESIGN 
This is an open-label, multi-center, single arm, phase II study to assess the anti-tumor activity and 
safety of bemcentinib in combination with pembrolizumab in patients with previously treated 
advanced adenocarcinoma of the lung. 
The study will enroll three cohorts of patients with previously treated, advanced adenocarcinoma 
of the lung: Cohort A will consist of patients who received a maximum of one prior line of 
platinum-containing chemotherapy and no prior immunotherapy of any kind. Cohort B will consist 
of patients with a maximum of one prior line of an anti-PD-(L)1 therapy (monotherapy). Cohort 
C will consist of patients who received a maximum of one prior line of therapy with an anti-PD-
(L)1 therapy in combination with a platinum-containing chemotherapy.
Cohort A will utilize a 2-stage, single-arm design, Simon’s 2-stage design1 with a single interim 
(Stage 1) analysis and a final (Stage 2) analysis. The interim (Stage 1) analysis will be conducted 
for the Data Review Committee (DRC) when 22 patients are evaluable (EE) for Objective 
Response Rate (ORR). If 3 or fewer responses are observed in up to 22 (EE) patients, the cohort 
will be terminated in favor of the null hypothesis for futility, and no further participants will be 
recruited. When at least 4 patients have an observed response at the interim analysis, up to a further 
26 patients may be evaluated (EE), for a total of 48 evaluable (EE) patients (see Section 8.1), 
taking the overall risk benefit of the combination into account. 
Cohort B will utilize a single-arm, Simon’s 2-stage design with 2 interim analyses and a final 
analysis. The interim analysis for Stage 1 will be conducted for DRC review when 13 patients are 
evaluable (EE) for ORR. If 0 responses are observed in up to 13 (EE) patients, the cohort will be 
terminated in favor of the null hypothesis for futility, and no further participants will be recruited. 
When at least 1 patient has an observed response at the interim (Stage 1) analysis, up to a further 
16 patients may be evaluated, for a total of 29 (EE) patients (see Section 8.1), taking the overall 
risk-benefit of the combination into consideration. The interim analysis for Stage 2 will be 
conducted once all patients have been treated and/or followed up for at least 12 months. The 
final analysis for cohort B will occur at the time of study completion – see Section 8.6 for details. 
Cohort B will assess the anti-tumor activity and safety of bemcentinib when given in 
combination with pembrolizumab in patients with advanced adenocarcinoma of the lung with 
a maximum of one prior line of an anti-PD-(L)1 therapy (monotherapy).  
Cohort C will utilize a single-arm, Simon’s 2-stage design with 2 interim analyses and a final 
analysis. The interim analysis for Stage 1 will be conducted for DRC review when 13 patients are 
evaluable (EE) for ORR. If 0 responses are observed in up to 13 (EE) patients, the cohort will be 
terminated in favor of the null hypothesis for futility, and no further participants will be recruited. 
When at least 1 patient has an observed response at the interim analysis, up to a further 16 
patients may be evaluated, for a total of 29 (EE) patients (see Section 8.1), taking the overall 
risk-benefit of the combination into consideration. The interim analysis for Stage 2 will be 
conducted once all patients have been treated and/or followed up for at least 12 months. The final 
analysis for cohort C will occur at the time of study completion – see Section 8.6 for details. 
Cohort C will assess the anti-tumor activity and safety of bemcentinib when given in 
combination with pembrolizumab in patients with advanced adenocarcinoma of the lung with a 
maximum of one prior line of treatment with an anti-PD-(L)1 therapy in combination with a 
platinum-containing chemotherapy.  
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           56 of 126 
Bemcentinib will be administered orally once daily. On the first 3 days of administration, the 
bemcentinib dose will be a ‘loading’ dose of 400 mg on Days 1, 2 and 3. From Day 4 onwards, 
patients will receive a daily dose of 200 mg. A dose of 200 mg pembrolizumab will be given by 
intravenous (i.v.) infusion over 30 minutes every 3 weeks in all patients. The 3-weekly 
pembrolizumab dosing schedule will be used to define 3-week treatment cycles throughout the 
treatment period of the study. 
The bemcentinib and pembrolizumab dose levels selected for this study are summarized in Table 9. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
Table 9: Bemcentinib and Pembrolizumab Dosing 
Loading Dose: 
Daily Dose: 
Bemcentinib: 
Days 1, 2 & 3 
Day 4 onwards 
Dose level 
-
-
Dose level -1 -
-
Dose 
Regimen 
Pembrolizumab 
200mg 
Day 1 of each cycle 
Frequency --
Frequency 
Every 
3 weeks 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Route of 
administration 
• • 
Route of 
administration 
IV 
Dosing of both drugs will commence on Day 1. On days when both bemcentinib and 
pembrolizumab are given, pembrolizumab will be given first and patients will be observed for 
1 hour for infusion and other adverse events. Bemcentinib may then be administered. 
4.1 
Cohort A - Safety Run-In 
Pembrolizumab has not previously been combined with bemcentinib in patients (in any indication) 
and therefore, a safety nm-in will include a total of 12 patients. The internal DRC will conduct a 
review of the safety data from the first 6 patients who have had the potential to be followed for at 
least 6 weeks (minimum 2 cycles), and then again after a further 6 patients (12 patients in total) 
have had the potential to be followed for at least 6 weeks. At each of these safety reviews, the DRC 
will consider the rate of bemcentinib dose reductions and the rate of permanent discontinuation 
from bemcentinib and pembrolizumab. 
The DRC will consider whether to recommend a lower dose of bemcentinib ( dose level -1) for 
¼tients. Dose level -1 is defined as - bemcentinib on Days 1, 2 & 3, followed by 
- from Day 4 onwards.
For the safety nm-in reviews, each patient will have had the potential to receive (as a minimum):
•
2 cycles ofpembrolizumab.
•
Bemcentinib at- for 3 days, followed by- daily for~ 6 weeks.
The DRC will consist of Principal Investigators, the Sponsors' (BerGenBio and Merck) medical 
monitors, and invited expe1ts as required, will review all patient safety data, including SAEs, AEs, 
laborato1y and ECG results, dosing info1mation, including dose reductions and pe1manent 
discontinuations. 
4.2 
End of Stage 1 - Efficacy Analysis and Review of Emerging Risk-Benefit Profile 
For coho1t A, the DRC will meet to review the ORR after 22 patients have been followed up for 
at least 24 weeks The DRC will document the ORR and, if it favors the null hypothesis for futility, 
will recommend if the study should proceed to evaluate up to a farther 26 patients. For cohort B, 
after 1 response has been confiimed, a subgroup of the DRC will meet to confirm continuation to 
Stage 2 and evaluation of 16 farther patients. An interim analysis (for Stage 1) will be conducted 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
57 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           58 of 126 
after 13 evaluable patients have at least 1 on treatment scan and are evaluable (EE) for ORR . This 
data will be reviewed by the DRC. For cohort C, after 1 response has been confirmed, a subgroup 
of the DRC will meet to confirm continuation to Stage 2 and evaluation of 16 further patients. 
An interim analysis (for Stage 1) will be conducted after 13 evaluable patients have at least 1 
on treatment scan and are evaluable (EE) for ORR. This data will be reviewed by the DRC. 
See Section 8.2 for more information on the DRC. 
Where there is a suggestion of an immune response leading to a false categorization of disease 
progression, results from later tumor assessment scan time points may be used for the objective 
response assessment following the 2-stage single-arm design. The Sponsor may request ad-hoc 
DRC meetings at any time during the study to assess the safety data and review the need for dose 
modifications. For more details on the dose modification rules for bemcentinib 
and pembrolizumab, please refer to Section 6.6.1 and Section 6.6.2. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           59 of 126 
Figure 4: Study Flow Chart 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           60 of 126 
4.3 
Duration of Treatment 
Bemcentinib and pembrolizumab will be given until disease progression (in the absence of clinical 
deterioration, treatment can continue and disease progression should be confirmed after 4 weeks) 
or until an unacceptable toxicity has occurred which necessitates treatment withdrawal 
(Section 6.6), or until 106 weeks (35 cycles) equivalent to calendar months. If it is decided at the 
Stage 1 analysis of any cohort that the cohort is to be closed for recruitment, then participants who 
have stable disease, even in the absence of PR or CR, will continue to be treated.  
NB: Participants who are still on study treatment after 35 cycles and continue to show benefit from 
the study treatment will be offered access to bemcentinib (e.g., under expanded excess program or 
roll over study) outside the study, after discussion with the sponsor, prior to study closure. 
Patients who discontinue bemcentinib treatment (for reasons other than disease progression) may 
be able to continue with (monotherapy) pembrolizumab until 106 weeks (that is, 35 completed 
cycles of pembrolizumab, equivalent to 24 calendar months).  
Patients who discontinue pembrolizumab (for reasons other than disease progression) may be able 
to continue with bemcentinib (monotherapy) upon approval by the Sponsor until Study Closure.  
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           61 of 126 
 
5 
STUDY SCHEDULE 
The study consists of a Screening period, Treatment period, Post Treatment Visit and Follow-up 
period. Patients will attend the clinic for Screening period assessments up to 28 days before 
receiving the first dose of study treatment. The Post Treatment Visit will occur 30 days (+/- 3 days) 
after the patient has discontinued both study treatments. All patients will continue in follow-up 
visits and continue to have their disease assessed and scanned (unless progression of disease has 
already been confirmed) and for survival status. 
The study schedule will continue in keeping with the Study Assessment calendar. Patients will be 
required to visit the study sites for each study visit (which includes each pembrolizumab dose). 
From Cycle 1 Day 8 onwards, a tolerance window of +/- 3 days is permitted relative to Day 1. 
Pembrolizumab that cannot be given within these tolerance windows will be treated as a missed 
dose, although it is acceptable to have a pembrolizumab dose interruption for up to 3 weeks for 
reasons other than toxicity. See Section 6.6.2 for details on pembrolizumab related toxicity dose 
interruption, including the duration of dose interruption. 
It is important that the calendar schedule for tumor assessment relative to Cycle 1 day 1 is 
maintained (subject to permitted tolerance windows). If treatment administration is misaligned 
with weeks (e.g. because of treatment delay), the tumor assessment schedule should be maintained 
by week number (Table 3, Table 4, Table 5 and Table 6). The schedule of disease assessment is 
every 12 weeks once a patient has stopped one or both or completed their (combination) treatment 
in the absence of progression. Assessments requiring specific timing relative to the bemcentinib 
or pembrolizumab dose are described in the footnotes to Schedule of Study Assessments - Table 4, 
Table 5, and Table 6. 
5.1 
Schedule of Study Assessments 
This section provides a list of study assessments described by visit. All procedures and assessments 
should be conducted pre-dose unless otherwise specified. A summary of this information is also 
provided in Schedule of Study Assessments - Table 4, Table 5 and Table 6 and associated 
footnotes. Additional assessments may be conducted as clinically indicated. 
5.1.1 
Schedule of Study Assessments – Year 1, Year 2 and beyond Cycle 35 
Screening (up to 28 days prior to Day 1) 
∼
Demographics - gender, ethnicity, race, age (birth month and year)
∼
Medical history
∼
Inclusion/exclusion checks
∼
Pregnancy or FSH test (as appropriate)
∼
ECOG PS
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
Coagulation
∼
Urinalysis
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           62 of 126 
∼
Thyroid function tests
∼
Echocardiogram (or MUGA)
∼
ECG (triplicate tests)
∼
Tumor assessment scans
∼
Disease Assessment
∼
Tumor biopsy (fresh tissue mandatory; archival optional)
∼
Biomarkers
∼
Concomitant medication
Cycle 1, Day 1 (21-day cycle) 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
Coagulation
∼
Urinalysis
∼
ECG (triplicate tests; pre-dose and 6 h post bemcentinib dose)
∼
Biomarkers (if not collected at Screening)
∼
Pembrolizumab dosing (200 mg fixed dose) - infusion
∼
Bemcentinib oral dosing
∼
PK sampling - bemcentinib
 pre-dose, 2, 4, 6 & 8 hours post dose 
∼
PK sampling for storage - pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 1, Day 2 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
ECG (triplicate test; pre-dose)
∼
Bemcentinib oral dosing
∼
PK sampling - bemcentinib
 (pre-dose) 
∼
PK sampling for storage – pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 1, Day 3 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
ECG (triplicate test; pre-dose)
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           63 of 126 
∼
Bemcentinib dosing
∼
PK sampling - bemcentinib pre-dose, 2, 4, 6 & 8 hours post dose
∼
PK sampling for storage – pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 1, Day 4 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
ECG (triplicate test; pre-dose)
∼
Biomarkers
∼
Bemcentinib dosing
 (daily oral dosing 21-day cycle) 
∼
PK sampling - bemcentinib (pre-dose)
∼
PK sampling for storage – pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 1, Day 8 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
Coagulation
∼
Urinalysis
∼
ECG (triplicate test; pre-dose)
∼
Biomarkers
∼
Bemcentinib dosing
 (daily oral dosing 21-day cycle) 
∼
PK sampling - bemcentinib (pre-dose)
∼
PK sampling for storage – pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 1, Day 15 
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
Coagulation
∼
Urinalysis
∼
ECG (triplicate test; pre-dose)
∼ 
Bemcentinib dosing 
 (daily oral dosing 21-day cycle) 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           64 of 126 
∼
PK sampling bemcentinib (pre-dose)
∼
PK sampling for storage – pembrolizumab (pre-dose)
∼
Adverse events
∼
Concomitant medication
Cycle 2- Cycle 3 Day 8, Day 15 (every week) 
∼
Clinical chemistry
∼
Adverse events
∼
Concomitant medication
Cycle 2-35 (every 3 weeks), Day 1 
∼
Pregnancy test (if applicable)
∼
ECOG PS
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
∼
Hematology
∼
Coagulation
∼
Urinalysis (performed on Cycle 2 Day 1 only)
∼
Thyroid function tests (performed after every 2 cycles i.e., Cycles 3, 5, 7, 9, 11, 13,
15, 17 in Year 1 and then Cycles 19, 21, 23, 25, 27, 29, 31, 33, 35 in Year 2)
∼
ECG (triplicate test; pre-dose)
∼
Echocardiogram (or MUGA) (performed at Cycles 9, 17, 25 and 33)
∼
Tumor assessment scans (performed at cycles 4, 7, 10, 13, 16, 20, 24, 28, 32 or
weeks 10, 19, 28, 37, 46, 58, 70, 82, 94, 106, and then every 12 weeks until
progression)
∼
Disease assessment (performed at cycles 4, 7, 10, 13, 16, 20, 24, 28, 32 or weeks 10,
19, 28, 37, 46, 58, 70, 82, 94, 106, and then every 12 weeks until progression)
∼
Tumor biopsy (up to 2 optional on treatment biopsies)
∼
Biomarkers (performed only at Cycles 2-9)
∼
Pembrolizumab dosing 200 mg fixed dose (infusion)
∼
Bemcentinib dosing
 (daily oral dosing 21-day cycle) 
∼
PK sampling bemcentinib (pre-dose cycles 2 and 3 only)
∼
PK sampling - pembrolizumab (pre-dose cycles 2 and 3 only)
∼
Adverse events
∼
Concomitant medication
Cycle 36 – 71 (every 3 weeks), Day 1 
∼
Pregnancy test (if applicable)
∼
ECOG PS
∼
Vital signs
∼
Physical examination
∼
Clinical chemistry
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Hematology 
Thyroid function tests (performed after every 2 cycles e.g., Cycles 37, 39, 41, 43) 
ECG (triplicate test; pre-dose) 
Tumor assessment scans (performed eve1y 12 weeks until progression) 
Disease assessment (perfo1med every 12 weeks until progression) 
Tumor biopsy (up to 2 optional on treatment biopsies) 
Bemcentinib dosing- (daily oral dosing 21-day cycle) 
Adverse events 
Concoinitant medication 
Post Treatment Visit (only after both study treatments are discontinued) +30 days from last 
dose of study treatment(s). 
ECOGPS 
Vital signs 
Physical exainination 
Clinical cheinistiy 
Hematology 
Coagulation 
Urinalysis 
Thyroid function tests 
ECG (t11plicate test) 
Tumor assessment scans (where applicable - for example to confom progression) 
Disease assessment (where applicable - for example to confirm progression) 
Adverse events 
Concoinitant medication 
Tumor biopsy ( optional) at progression 
Follow-Up (if the patient has had a Post Treatment visit) eve1y 12 weeks 
5.2 
Tumor assessment scans (where applicable; eve1y 12 weeks until disease 
progression) 
Disease assessment (where applicable; eve1y 12 weeks until progression) 
Subsequent anti-cancer treatment 
Concoinitant mediation (where applicable) 
Adverse events (where applicable, see Section 7.4 and Section 7.5) 
Survival status (this can be done by telephone) 
Volume of Blood Sampling 
Total blood volumes required during study pa1ticipation will be provided in the Informed Consent 
fo1m provided to each patient. The Laborato1y Manual will also desc11be unit and total blood 
volumes and provide examples based on various durations on study. Effo1ts will be made to liinit 
PK and PD blood-letting during the sh1dy where on-going data analysis during the sh1dy suggests 
redundancy in sampling. Any such reductions in requirements for PK and PD blood sampling will 
be described and maintained in the Laboratory Manual. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
65 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           66 of 126 
5.3 
Description of Study Interventions and Assessments 
Details of the procedures to be followed for specified study assessments are provided. Additional 
assessments may be carried out as clinically indicated. 
5.3.1 
Demography and medical history 
There will be a baseline assessment of demography (gender, race, ethnicity age (birth month and 
year), and medical history conducted at Screening to confirm eligibility and to record significant 
medical history, including smoking history, PD-(L)1 status on diagnosis (cohort B and C patients 
only) and concurrent illnesses in the CRF. 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 allocation need to be reported as an adverse event if the 
event causes the patient to be excluded from the trial or is a result of a protocol specific intervention 
(Section 7.1). 
5.3.2 
Pregnancy and FSH test 
Female patients of reproductive potential will have a pregnancy test carried out at Screening. This 
test must be carried out within 3 days prior to first study drug administration. A urine test is 
acceptable; however, a positive or equivocal urine test must be confirmed by a blood test. Patients 
confirmed as pregnant will be excluded from participation in the clinical study. 
Female patients of reproductive potential will continue to have a pregnancy test before each cycle 
of pembrolizumab or at least monthly. 
Female patients who require documented confirmation of post-menopausal status will have their 
FSH levels assessed at Screening. Where post-menopausal status is not confirmed, patients will be 
required to undergo pregnancy testing per protocol to confirm suitability to proceed to dosing. 
5.3.3 
ECOG performance score 
ECOG PS will be assessed at the times given in Schedule of Study Assessments - Table 4, Table 5 
and Table 6. Details of the ECOG PS categories are presented in Appendix A. Patients must be 
confirmed as ECOG PS 0 or 1 at Screening in order to be eligible for study participation. 
5.3.4 
Vital signs 
Vital sign parameters will be taken at the times given in Schedule of Study Assessments - Table 4, 
Table 5 and Table 6. The date and time of collection will be recorded in the source data and on the 
CRF. 
Vital sign parameters will consist of measurements of temperature, resting heart rate, seated blood 
pressure and respiratory rate. 
If any clinically significant findings are identified during the assessment of vital signs, the 
Investigator will record it as part of the medical history prior to start of dosing and as an AE post 
dose, where the finding represents a change from baseline. Findings identified prior to start of 
dosing must be checked against the study exclusion criteria (see Section 3.2). 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           67 of 126 
5.3.5 
Physical exam 
A physical examination, including measurement of weight, will be taken at the times given in 
Schedule of Study Assessments - Table 4, Table 5 and Table 6. The patient’s height will be 
measured at Screening. The patient’s weight will also be assessed at Screening and at the start of 
every cycle. Height and body weight will be obtained while the patient is wearing light clothing 
(without shoes). 
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. 
If any clinically significant findings are identified during the physical examination, the Investigator 
will record it as part of the medical history prior to start of dosing and as an adverse event post 
dose, where the finding represents a change from baseline. 
5.3.6 
Clinical chemistry, hematology, coagulation and urinalysis 
Blood and urine samples for determination of clinical chemistry, hematology, coagulation and 
urinalysis parameters will be taken at the times given in Schedule of Study Assessments – Table 4, 
Table 5 and Table 6 and prior to administration of study treatment. The date and time of collection 
will be recorded in the source data and on the CRF. 
All testing will be performed at each site’s local laboratory. Coagulation parameters may be 
assessed from the hematology sample. 
Copies of laboratory accreditation certificates and reference ranges will be obtained from each 
study site prior to the analysis of their first patient sample. 
The laboratory variables to be measured are described in Appendix E. 
If any clinically significant findings are identified from the safety lab assessments, the Investigator 
will record it as part of the medical history prior to start of dosing and as an AE post dose, where 
the finding represents a change from baseline. Findings identified prior to start of dosing must be 
checked against the study inclusion and exclusion criteria (Section 3.1 and Section 3.2). 
5.3.7 
Thyroid function test 
Blood samples for thyroid function testing will be taken at the times given in Schedule of Study 
Assessment Table 4, Table 5 and Table 6. The date and time of collection will be recorded in the 
source data and on the CRF. 
The thyroid assessment panel should include:  
•
Triiodothyronine (T3) or Free Triiodothyronine (FT3)
•
Free thyroxine (FT4)
•
Thyroid stimulating hormone (TSH).
All testing will be performed at each site’s local laboratory. This assessment may be 
performed from the clinical chemistry sample (see Section 5.3.6). Copies of laboratory 
accreditation 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           68 of 126 
certificates and reference ranges will be obtained from each study site prior to the analysis of their 
first patient sample. Laboratory variables to be measured are described in Appendix E. 
If any clinically significant findings are identified, the Investigator will record it as part of the 
medical history prior to start of dosing and as an AE post dose, where the finding represents a 
change from baseline. Findings identified prior to start of dosing must be checked against the study 
inclusion criteria (see Section 3.1). 
5.3.8 
Echocardiography or MUGA 
An echocardiography or MUGA assessment will be performed at Screening, and after every 6 
months (every 8 cycles thereafter i.e., Cycle 9, Day 1; Cycle 17, Day 1; Cycle 25, day 1; Cycle 33, 
Day 1) until the end of 2 years. 
Clinically significant findings identified prior to start of dosing must be checked against the 
study exclusion criteria (Section 3.2). 
Patients who discontinue bemcentinib, but continue with monotherapy pembrolizumab, will stop 
undergoing an echocardiogram or MUGA assessment. Their final echocardiogram/MUGA 
assessment will occur if their next scheduled assessment is within the next 6 weeks (of 
discontinuing bemcentinib). 
5.3.9 
Electrocardiogram 
A resting 12-lead ECG will be performed at the times given in Schedule of Study Assessments - 
Table 4, Table 5 and Table 6. Each assessment time point must be performed in triplicate before 
starting treatment with bemcentinib.  
All 12-lead ECGs should be recorded while the patient is in the supine position. 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 patients. 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 the start of dosing, and as an AE post dose where the finding 
represents a change from baseline. Clinically significant findings identified prior to start of dosing 
must be checked against the study exclusion criteria (Section 3.2). 
Note that the average value of the three assessments performed at each time point should be 
applied, except at Screening, where both the Screening and pre-dose Cycle 1 Day 1 assessments 
should be combined. Patients may be excluded based on the initial triplicate assessment at 
Screening. 
Patients who discontinue bemcentinib but continue with monotherapy pembrolizumab will stop 
undergoing an ECG. 
Patients who have a bemcentinib interruption of for 14 days due to QTc prolongation or 12 weeks 
for immune-related toxicities (see Table 12 and Table 13) will require an ECG twice weekly for 
the 2 weeks following recommencement of bemcentinib daily dosing. This is to ensure cardiac 
safety monitoring whilst bemcentinib returns to stead state. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           69 of 126 
 
5.3.10 
Tumor Assessment Scans 
Efficacy endpoints in this study, including ORR, DoR, PFS will all be based on tumor assessment 
scan evaluation by RECIST 1.12. 
RECIST assessments will be performed at the times given in Schedule of Study Assessments - 
Table 4, Table 5, Table 6 and Table 7 using contrast-enhanced CT (preferred method) or MRI 
assessments of chest, abdomen, and pelvis. Additionally, x-ray and bone scans will be used as 
appropriate. Additional anatomy should be imaged based on signs and symptoms of individual 
patients at baseline and follow-up. 
Baseline assessments should be performed no more than 28 days before start of study treatment, 
and ideally should be performed as close as possible to the start of study treatment. The Screening 
scan assessments must confirm the patient has measurable disease per RECIST 1.12 (see Inclusion 
Criteria Section 3.1). 
For each patient, the same modality used at Screening 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 assessments. 
All radiological and non-radiological (e.g., MRI) scans will be reviewed by the local site 
investigator; and if possible, stored electronically (de-identified with the patient’s notes) at site.  
A maximum of 5 target lesions, maximum of 2 per organ, must be selected at baseline. All target 
lesions are measurable. Target lesions should be selected on the basis of their size (longest diameter 
for non-nodal lesions or short axis for nodal lesions), but in addition should be those that lend 
themselves to reproducible repeated measurements. All remaining lesions present at baseline are 
considered non target, irrespective of whether they are measurable. 
Disease assessments will be performed as per the schedule described in Table 4 and Table 5 – that 
is, every 9 weeks ±7 days for the first 46 weeks relative to the date of first treatment administration 
and then every 12 weeks ±7 days thereafter until confirmed objective disease progression as 
defined by RECIST 1.12 (irrespective of a delay to treatment or the reason for stopping treatment 
or subsequent therapy). 
Any other sites at which new disease is suspected should also be adequately imaged at a follow-up 
visit. 
If an unscheduled assessment is performed and the patient has not progressed, every attempt should 
be made to perform the subsequent assessments at their scheduled visits. 
In addition to performing further scans where clinically indicated, scans also should be performed, 
as appropriate, to confirm response or disease progression. 
5.3.11 
Disease assessment 
A disease assessment according to RECIST 1.12 will be performed and recording in the CRF 
whenever a tumor assessment scan is made during the Treatment period, Post Treatment Visit or 
during Follow Up Visits. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           70 of 126 
For more information on data evaluation by RECIST 1.12 for studies with checkpoint inhibitors, 
please refer to Section 8.5. 
5.3.12 
Biomarkers 
Evaluation of biomarkers will be performed at the time points described in Schedule of Study 
Assessments - Table 4, Table 5, Table 6 and Table 7. 
Blood samples will be collected at these time points to prepare PMBC and blood samples for 
assessment of Axl inhibition and other relevant markers including sAxl such as MAPK signaling 
pathway intermediates (ERK/pERK), pAxl expression and T-cell populations, Akt, pAkt, 
SLFN11, Bcl2, and Puma. 
Full details of the blood volumes required, plus requirements for sample collection, handling and 
shipment to the assigned central laboratory, will be described in Laboratory Manual for the study. 
5.3.13 
Tumor Sample Requirements 
All patients are required to have a fresh (newly acquired) tumor biopsy. This can be taken up to 3 
months before treatment starts provided the patient has not received any further chemotherapy or 
immunotherapy, or other anti-cancer therapy in the intervening period and that sufficient tumor 
tissue is available. 
Tumor specimens are to be submitted in sufficient quantity to allow for PD-L1 
immunohistochemistry (IHC) and Axl IHC analysis (see the Pathology Manual). 
Samples with limited tumor content (<100 viable tumor cells), cytology, cell block, decalcified or 
formalin fixed but previously frozen, frozen sample, plastic embedded, bone, bone marrow, clot 
and fine needle aspirates are inadequate for defining tumor PD-L1 and Axl status. 
Axl expression can only be obtained from a fresh (newly acquired) tumor tissue sample. PD-L1 
expression can be determined from either a fresh (newly acquired) or archival sample. In all cases, 
the tumor tissue must not have been previously irradiated. 
Different testing laboratories will be used for Axl kinase and PD-L1 expression. 
The fresh (newly acquired) tumor tissue sample will be either newly obtained core needle biopsy 
(minimum gauge 18) or newly obtained excisional biopsy. 
The following tumor tissue alternatives are available (all options require fresh tumor tissue sample; 
however, if there is insufficient fresh tumor tissue available, the 3rd option below allows the 
submission of archival tissue in addition to the fresh tissue sample): 
•
Where only a core needle biopsy is used, a minimum of 4 core (with 1-cm tumor in each
core) biopsy samples are required. These should be placed in formalin and processed into
2 single paraffin embedded (FFPE) blocks (2 cores in one block and 2 cores in the other
block) within 24-48 hours.
•
Alternatively, where only a newly obtained excisional biopsy sample is used, this biopsy
should be processed into 2 paraffin embedded (FFPE) blocks within 24-48 hours.
•
Alternatively, 2 core (with 1-cm tumor in each core) needle (fresh tumor) biopsies or a
single newly obtained excisional biopsy sample can be submitted (processed into one FFPE 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           71 of 126 
block), together with either an archival (FFPE) tumor tissue block or a minimum of 
10 unstained slides each 5 µm cut from the archival tumor sample block. 
If an archival tumor tissue block is to be sent, it is suggested that a minimum of 10 unstained slides 
each 5 µm cut from the archival tumor sample block must be sent (rather than sending the whole 
archival block) and clearly labelled as having come from an archival block. 
Optional ‘on study’ tumor tissue (fresh tissue) biopsies can be conducted on up to 2 separate 
occasions on suitable lesions (for example, lesions that have progressed). Separate patient consent 
is required for these ‘on study’ biopsies. 
Full details of the requirements for both fresh and archival biopsy sample collection, handling and 
shipment to the assigned (central) laboratories, will be described in Pathology and Laboratory 
Manuals for the study. 
5.3.14 
Pharmacokinetics 
Blood samples will be collected for the evaluation of the levels of bemcentinib and pembrolizumab 
in plasma at the time points described in Schedule of Study Assessments - Table 4, Table 5, Table 6 
and Table 7. 
Nominal PK blood sampling times should be adhered to as closely as possible. It is essential that 
the actual time and date of collection of each blood sample be recorded in the patient’s records and 
in the CRF. 
Full details of sample collection and handling for these samples will be described in Laboratory 
Manual for the study. 
Full details of the blood volumes required, plus requirements for sample collection, handling and 
shipment to the assigned central laboratory, will be described in Laboratory Manual for the study. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
6 
STUDY MEDICATION AND ADMINISTRATION 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Investigational Medical Product (IMP) will be provided by the Sponsor as summarized in 
Table 10. Both bemcentinib and pembrolizumab will be labelled in compliance with the Good 
Manufacturing Procedure (GMP) Annex 13 requirements or other applicable local regulatory 
guidelines. 
Table 10: Product Descriptions 
Product Name &_P_ot_e_nc y __________ 
D_o_sa...._e_F_o1_·m 
_____________ -1 
BGB324 
HPMC ca sule 
Solution for Injection 
6.1 
Preparation and Dosing of Study Treatments 
Fmther details on preparation and administration of both bemcentinib and pembrolizumab are 
provided in the Pha1macy Manuals. 
6.1.1 
Bemcentinib 
Bemcentinib is provided in bottles containing a specified number of capsules per bottle to dispense 
to the patients. Patients will be asked to take the specified number of capsules for their prescribed 
dose on an empty stomach at a regular time each day with water. Patients should not eat for at least 
one hour following bemcentinib. Rescue treatment with antacids, proton pump inhibitors and 
histamine receptor 2 inhibitors can be initiated, provided they are taken in the evening. On 
pembrolizumab dosing days, patients will be asked not to take their bemcentinib dose before 
coming into the clinic. On these days, pembrolizumab will be administered first, and the patient 
observed for 1 hour after the end of infosion (for infosion and other AEs), prior to taking their 
bemcentinib dose (on an empty stomach and with water). 
6.1.2 
Pembrolizumab 
Pembrolizumab will be administered at a dose of 200 mg (two vials) given as a 30-minute i.v. 
infusion through an intravenous line containing a sterile, non-pyrogenic, low-protein-binding 0.2-
5 micron in-line or add-on filter. Dosing will be on Day 1 of each 3-week treatment cycle. 
Trial treatment of pembrolizumab may be administered up to 3 days before or after the scheduled 
Day 1 of each cycle due to administrative reasons 
Sites should make eve1y 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 between -5 minutes 
and +10 minutes is pe1mitted i.e., infusion time may be 30 minutes -5 min/+ 10 min. 
6.2 
Treatment Compliance 
The patient will be asked to bring all bottles, including the empty ones, with them to each study 
visit to check compliance and for the Dmg Accountability and Dose Log to be completed in the 
eCRF. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
72 of 126 
C
Confldentlal 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
           73 of 126 
At each visit the Investigator or study staff will question the patient about the proper intake. 
Proper intake, missed doses, or failures in compliance will be recorded in the patient’s file and 
eCRF. The patient will be instructed as to the importance of taking their bemcentinib in accordance 
with instructions. 
6.3 
Storage of Study Treatments 
6.3.1 
Bemcentinib 
Bemcentinib will be shipped to the site and must be stored at the site in a secure location under 
controlled, ambient temperature conditions (<25 °C or <77 °F). Instructions for the storage of 
dispensed bemcentinib at home will be provided to every patient enrolled in the clinical study. 
6.3.2 
Pembrolizumab 
Pembrolizumab (in 10-mL glass vials) will be shipped to the site and must be stored as follows: 
•
Cold storage (2 oC – 8 oC; 36 oF- 46 oF);
•
Protect from light (a maximum of 24 hours exposure to light is permitted);
•
Do not freeze;
•
Do not shake.
6.4 
Drug Accountability
The Investigator shall take responsibility for and shall take all steps to maintain appropriate records 
and ensure appropriate supply, storage, handling, distribution and usage of trial treatments in 
accordance with the protocol and any applicable laws and regulations. The Investigator may assign 
some or all of the Investigator’s duties for drug accountability to an appropriate pharmacist. Roles 
and responsibilities of site staff will be recorded in the TMF. 
The investigator is responsible for keeping accurate records of the clinical supplies received from 
the Sponsor or designee, the amount dispensed to and returned by the patients and the amount 
remaining at the conclusion of the trial. For all trial sites, the local country Sponsor personnel or 
designee will provide documentation that must be completed for drug accountability and return, 
or local discard and destruction if appropriate. Where local discard and destruction is appropriate, 
the investigator is responsible for ensuring that a local discard / destruction procedure is 
documented. 
Certificates of delivery and return must be signed by the responsible pharmacist, and copies 
retained in the Pharmacy File. 
The medication provided for this study is for use only as directed in the protocol. It is the 
Investigator and their institution’s responsibility to establish a system for handling study drug so 
as to ensure that: 
•
deliveries of bemcentinib and pembrolizumab are correctly received by a responsible
person;
•
such deliveries are recorded;
•
study treatments are handled and stored safely and properly as stated on the label;
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
•
study drug is only dispensed to study patients in accordance with the protocol; and
•
any unused study diug is destroyed locally or rehuned for destruction in liaison with
the sh1dy monitor.
6.5 
Method of Enrolling Patient to Study Treatment 
Dming Screening, patients will be allocated a unique screening number from RA VE once written, 
info1med consent has been obtained. Patients will be identified by this number throughout the 
study. Once a Subject Number has been assigned, it cannot be used again. 
6.6 
Dose Modifications 
Note that 4 toxicities have been identified as being potentially overlapping with both bemcentinib 
and pembrolizumab - diaIThea, rash, renal toxicity and increased ALT ancVor AST. Please see 
Section 6.6.3 for the management of these toxicities. 
Other toxicities can be managed as described in Section 6.6.1 and Section 6.6.2. 
6.6.1 
Bemcentinib dose modification for toxicity 
As the study involves bemcentinib given in combination with pembrolizumab, the guidance of 
dose modification of bemcentinib for related toxicities was harmonized with pembrolizumab. If a 
patient experiences diug related toxicity that requires treatment with bemcentinib to be intem1pted, 
a delay of up to 12 weeks is pe1mitted to allow for resolution of toxicity. If, after a 12-week 
intem1ption, treatment-related toxicity has not resolved, treatment with bemcentinib needs to be 
discontinued pe1manently or ftuther dosing of bemcentinib should be discussed with the medical 
monitor. 
See Table 11 for detailed guidance on the dose modification ofbemcentinib. 
If treatment with bemcentinib is intem1pted, the relevant toxicity must have resolved to  Grade 1 
or baseline for treatment to recommence. 
Dose reduction of bemcentinib from 200 mg to 100 mg daily dose is allowed. Following dose 
reduction of bemcentinib to 100 mg daily dose, if the toxicity is resolved or rehuned to baseline, 
the dose ofbemcentinib can be increased to 200 mg daily. 
Table 11: Dose Modification of Bemcentinib for Toxicity 
Grade (CTCAE v 5.0) 
Recommended Dose Modification 
Grade 1 
Anv occurrence 
No dose modification reQuired 
Grade 2 
Any occurrence 
Interrupt treatment until toxicity returns to baseline or Grade 1 then resume 
bemcentinib at!! daily
If the patient deve ops the same toxicity at Grade 2, please discuss with 
medical monitor 
Grade 3 
Any occurrence 
Interrupt treatment until toxicity returns to baseline or Grade 1 
Resume bemcentinib at- daily for 1 cycle, then titrate u.o
daily. a daily dose 1s not tolerated, reduce the dose to 
daily. 
BGBC008 I PN-53 l - NSCLC Version 11.0 
26 January 2022 
74 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
Grade (CTCAE v 5.0) 
Grade 4 
1st occurrence 
Notes: 
Recommended Dose Modification 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
If the patient develops the same toxicity at Grade 3, please discuss with 
medical monitor 
Discontinue permanently or discuss with medical monitor 
• Treatment interruption for bemcentinib-related toxicity is allowed for a maximum of 12 weeks
• Dose reduction below- daily is not possible (a single capsule contains- bemcentinib)
• Patients being considered for dose reduction or permanent discontinuation ofbemcentinib, may be discussed
with the medical monitor
• Patients require an ECG twice weekly for 2 weeks after recommencing bemcentinib following an interruption
(see Section 5.3.9)
Treatment with bemcentinib can cause QTc prolongation. In order to reduce the risk of QTc 
prolongation, all effo1ts should be made to maintain the patient's semm potassium levels at 
>4 nunol/L during treatment with bemcentinib and for 2 weeks following completion of therapy
(at an unscheduled visit, if required). Serum calcium and magnesium should be measured and
reasonable effo1ts made to maintain at n01mal levels throughout the sh1dy treatment. Patients with
an average QTc of 480 ms should be closely monitored until the QTc falls below 480 ms;
electrolytes should be measured and coITected as necessa1y.
If a patient experiences QTc prolongation, bemcentinib dosing should be modified as outlined 
in Table 12, however, it is strongly advised to discuss any event of QTc prolongation with the 
medical monitor. Treatment with bemcentinib should be permanently discontinued in the 
presence of ventricular aIThythmia. 
Table 12: Dose Modification of Bemcentinib for QTc Prolongation 
OTcF 
Grade 1 (451-480 ms) 
Any occurrence 
Grade 2 (481-500 ms) 
1st and 2nd occurrence 
3rd and subsequent 
occurrence 
Recommended Bemcentinib Dose Modification 
No dose modification required 
Continue dosing and conduct weekly ECGs; 
•
if QTcF reduces to :'.SGrade 1 within 14 days from initial recording, no 
dose modification is required
•
if QTcF does not reduce to :'.SGrade 1 within 14 days from initial
recording, reduce dose to- daily and titrate it to- if
possible
At 3rd occurrence, interrupt bemcentinib dosing for :'.:,14 days and conduct weekly 
ECGs; . 
if QTcF reduces to :'.SGrade 1 within 14 days, restart bemcentinib at 
- dose and maintain at- for the remainder of the study;
. 
if QTcF does not reduce to :'.SGrade 1 within 14 days, discontinue 
treatment permanently or discuss with medical monitor 
At any subsequent occurrence, discontinue treatment permanently or discuss with 
medical monitor 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
75 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
OTcF 
,:Grade 3 (2501 ms) 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Recommended Bemcentinib Dose Modification 
Any occUITence 
For 1st occurrence, interrupt treatment for 94 days; 
. 
ifQTcF reduces to ::SGrade 1, reduce dose tollll daily, discontinue 
treatment if dose reduction is not possible or discuss with medical 
monitor 
. 
if QTcF does not reduce to ::SGrade 1, discontinue treatment or discuss 
with medical monitor 
For 2nd occurrence, discontinue treatment or discuss with medical monitor 
Ventricular arrhythmia 
Any occUITence 
Discontinue permanently 
Notes: 
• Serum calcium, magnesium and potassium should be measured regularly whilst receiving bemcentinib; all 
abnormal results should be corrected
• The mean QTcF value from triplicate ECG readings should be used when considering dose modification
• Treatment interruption for bemcentinib-related QTcF prolongation is only allowed for 14 days
• Dose reduction belowllll daily is not possible (a single capsule containsllll bemcentinib)
• Patients being considered for dose reduction or permanent discontinuation ofbemcentinib may be discussed
with the medical monitor
• Patients require an ECG twice weekly for 2 weeks after recommencing bemcentinib following an interruption
(see Section 5.3.9)
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
76 of 126 
C
Confldentlal 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Figure 5: Dose Modification ofBemcentinib fo1· Increased ALT/AST With 01· Without Increased Bilirubin 
-
I 
_,,, 
(>UlNto.3.0llUlH) 
I 
Nly Occurtnct 
I 
I ·-·
(>l.0-).01UUol) 
lnt,:1T1,Jpttn:etmcnt(tl:lr"f'tOU 
WUkSI 
monitor U'Ts twic.t • Wttt 
I 
i..... dixonĎ11UCputne.fttnt1yO!'diKun 
•1th tht tntdiallmOlll'!Or 
irimĐtoG1orđc:linewtnifi 
u weetsĒ:tcrioo, rt$Urt.-t 
1rirnpr-dt0Gt ortie;,:Wlewithin 
1--u WttkSWitll st 
•
• rutert .. 
ltflOt improv,ecstoGtorc.selint 
i..... witl'liftUWf:ckS(.Oor-.ithout 
ēs), diKontinue per,.,.ncnoyo 
CliS<IJU witri trlc mtdicel monitor 
I 
čreoel 
C>).0-to201ULN) 
I 
lntenupttrutm,tnttorupto U 
wo:ds, :ten stď enof!'lonitor 
LFTs twice• weet 
II i"'i',-otoG1 or ,:,-.line witriit1 
i---
Uwedsrui.ttr,uricentiniltiet -
It flot in<1proved to Gt Of c.seliftt 
-.itrain ll •cds,diKOl!bnutd 
petmel'ltnt1yordiscun .Otllot 
mcdicel monitor 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Noiway 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
77 of 126 
C Confldent111 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC 
Version 11.0 
26 January 2022 
78 of 126 
6.6.2 
Pembrolizumab dose modifications 
Adverse events (both non-serious and serious) associated with pembrolizumab exposure may 
represent an immunologic etiology. These immune-related AEs (irAEs) may occur shortly after 
the first dose or several months after the last dose of pembrolizumab treatment and may affect 
more than one body system simultaneously. Therefore, early recognition and initiation of treatment 
is critical to reduce complications. Based on existing clinical study data, most irAEs were 
reversible and could be managed with interruptions of pembrolizumab, administration of 
corticosteroids, and/or other supportive care. For suspected irAEs, adequate evaluation must be 
ensured to confirm etiology or exclude other causes. Additional procedures or tests such as 
bronchoscopy, endoscopy, or skin photography may be included as part of the evaluation. Based 
on the severity of irAEs, pembrolizumab must be withheld or permanently discontinued, and 
corticosteroids should be administered as per Table 13 below. See Section 6.11 for supportive 
care guidelines, including use of corticosteroids. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 
11.0 
26 January 2022 
79 of 126 
Table 13: Dose Modification and Toxicity Management Guidelines for Immune-related AEs Associated with Pembrolizumab  
General instructions: 
1.
Severe and life-threatening irAEs should be treated with IV corticosteroids followed by oral steroids. Other immunosuppressive treatment should
begin if the irAEs are not controlled by corticosteroids.
2.
Pembrolizumab must be permanently discontinued if the irAE does not resolve or the corticosteroid dose is not ≤10 mg/day within 12 weeks of
the last pembrolizumab treatment.
3.
The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue at least 4 weeks.
4.
If pembrolizumab has been withheld, pembrolizumab may resume after the irAE decreased to ≤ Grade 1 after corticosteroid taper.
Immune-related 
AEs 
Toxicity grade or 
conditions 
(CTCAE v5.0) 
Action taken to 
pembrolizumab 
irAE management with corticosteroid 
and/or other therapies  
Monitor and follow-up 
Pneumonitis 
Grade 2 
Withhold 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg prednisone or 
equivalent) followed by taper 
Monitor participants for signs and symptoms of 
pneumonitis 
Evaluate participants with suspected 
pneumonitis with radiographic imaging and 
initiate corticosteroid treatment 
Add prophylactic antibiotics for opportunistic 
infections 
Grade 3 or 4, or 
recurrent Grade 2 
Permanently 
discontinue 
Diarrhea / Colitis 
Grade 2 or 3 
Withhold 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg prednisone or 
equivalent) followed by taper 
Monitor participants for signs and symptoms of 
enterocolitis (i.e., diarrhea, abdominal pain, 
blood or mucus in stool with or without fever) 
and of bowel perforation (i.e., peritoneal signs 
and ileus). 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 
11.0 
26 January 2022 
80 of 126 
Recurrent Grade 3 
or Grade 4 
Permanently 
discontinue 
Participants with ≥ Grade 2 diarrhea suspecting 
colitis should consider GI consultation and 
performing endoscopy to rule out colitis.  
Participants with diarrhea/colitis should be 
advised to drink liberal quantities of clear fluids. 
If sufficient oral fluid intake is not feasible, fluid 
and electrolytes should be substituted via i.v. 
infusion. 
AST / ALT 
elevation or 
Increased 
bilirubin 
Grade 2 
Withhold 
Administer corticosteroids (initial 
dose of 0.5 to 1 mg/kg prednisone or 
equivalent) followed by taper 
Monitor with liver function tests (consider 
weekly or more frequently until liver enzyme 
value returns to baseline or is stable) 
Grade 3 or 4 
Permanently 
discontinue 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg prednisone or 
equivalent) followed by taper 
Type 1 diabetes 
mellitus (T1DM) 
or 
Hyperglycemia 
Newly onset 
T1DM or 
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of β-cell 
failure 
Withhold 
Initiate insulin replacement therapy 
for participants with T1DM  
Administer antihyperglycemic in 
participants with hyperglycemia  
Monitor participants for hyperglycemia or other 
signs and symptoms of diabetes. 
Hypophysitis 
Grade 2 
Withhold 
Administer corticosteroids and initiate 
hormonal replacements as clinically 
indicated.   
Monitor for signs and symptoms of hypophysitis 
(including hypopituitarism and adrenal 
insufficiency)  
Grade 3 or 4 
Withhold or 
permanently 
discontinue1 
Hyperthyroidism 
Grade 2 
Continue 
Monitor for signs and symptoms of thyroid 
disorders.  
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 
11.0 
26 January 2022 
81 of 126 
Grade 3 or 4 
Withhold or 
permanently 
discontinue1 
Treat with nonselective beta-blockers 
(e.g., propranolol) or thionamides as 
appropriate  
Hypothyroidism 
Grade 2-4 
Continue 
Initiate thyroid replacement hormones 
(e.g., levothyroxine or liothyroinine) 
per standard of care 
Monitor for signs and symptoms of thyroid 
disorders.  
Nephritis and 
Renal 
dysfunction 
Grade 2 
Withhold 
Administer corticosteroids 
(prednisone 1 to 2 mg/kg or 
equivalent) followed by taper 
Monitor changes of renal function 
Grade 3 or 4 
Permanently 
discontinue 
Neurological 
toxicities 
Grade 2 
Withhold 
Based on severity of AE, administer 
corticosteroids 
Ensure adequate evaluation to confirm etiology 
and/or exclude other causes 
Grade 3 or 4 
Permanently 
discontinue 
Myocarditis 
Grade 1 
Withhold 
Based on severity of AE, administer 
corticosteroids 
Ensure adequate evaluation to confirm etiology 
and/or exclude other causes 
Grade 2, 3, or 4 
Permanently 
discontinue 
Exfoliative 
dermatologic 
conditions 
Suspected SJS, 
TEN, or DRESS 
Withhold 
Based on severity of AE, administer 
corticosteroids 
Ensure adequate evaluation to confirm etiology 
or exclude other causes 
Confirmed SJS, 
TEN, or DRESS 
Permanently 
discontinue 
All other irAEs 
Persistent Grade 2 
Withhold 
Based on type and severity of AE, 
administer corticosteroids  
Ensure adequate evaluation to confirm etiology 
and/or exclude other causes 
Grade 3 
Withhold or 
discontinue based 
on the type of 
event. Events that 
require 
discontinuation 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 
11.0 
26 January 2022 
82 of 126 
include and are not 
limited to: 
encephalitis, other 
clinically important 
irAEs (e.g., 
vasculitis and 
sclerosing 
cholangitis) 
Recurrent Grade 3 
or Grade 4  
Permanently 
discontinue 
1Withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician.  
NOTE:  
Non-irAEs will be managed as appropriate, following clinical practice recommendations. 
For participants with Grade 3 or 4 immune-related endocrinopathy where withhold of pembrolizumab is required, pembrolizumab may be resumed when 
AE resolves to ≤ Grade 2 and is controlled with hormonal replacement therapy or achieved metabolic control (in case of T1DM). 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Dosing intem.1ptions are permitted in the case of medical / surgical events or logistical reasons not 
related to study therapy e.g., elective surge1y, unrelated medical events, patient vacation, and/or 
holidays. Patients should be placed back on study therapy within 3 weeks of the scheduled 
intem1ption, unless othe1wise discussed with the Sponsor. The reason for intem1ption should be 
documented in the patient's study record. 
6.6.3 
Dose modifications for bemcentinib and pembrolizumab for overlapping 
toxicities 
Four tox1c1t1es are identified as potentially overlapping with both bemcentinib and 
pembrolizumab: dianhea, rash (including de1matitis, pruritus), renal toxicity (renal failure, semm 
creatinine elevation, nephritis) and increases in ALT and AST. 
See also, Suppo1tive Care Guidelines for Pembrolizumab - Section 6.11. 
6.6.3.1 
Dose modifications for diarrhea 
Patients may continue with baseline anti-dianheal medications throughout the study treatment with 
pembrolizumab and bemcentinib. If a patient experiences an increase in dianheal symptoms after 
staiting bemcentinib they may increase the dose of anti-dianheal medication such as loperamide 
during the first week of treatment only. Sta1ting ti·eatment with loperamide is also acceptable 
during this period. Thereafter any increased dianheal symptoms should be reported to the 
investigator immediately and further medication should not be given. See Table 14. 
Table 14: Pembrolizumab and Bemcentinib Dose Modification for Diarrhea 
Dianbea 
Pembrolizumab 
Bemcentinib 
Grade 1 
No dose modification needed 
No dose modification needed 
Grade 2-3 
Withhold for up to 12 weeks oflast 
Withhold for up to 12 weeks oflast 
dose 
dose 
•
If resolved to Grade O or 1,
• If resolved to Grade O or 1,
restart pembrolizumab
restart bemcentinib at-
•
Permanently discontinue if not
• If not resolved to Grade O or 1
resolved to Grade O or 1, or
permanently discontinue or
there is an inability to reduce
discuss with the medical monitor
corticosteroid to :'.Sl O mg
(prednisone or equivalent) per 
day
Recurrent Grade 3 or Grade 4 
Permanently discontinue 
Permanently discontinue 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
83 of 126 
C
Confidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
6.6.3.2 
Dose modifications for rash (including dermatitis, pruritus) - Table 15 
Table 15: Pembrolizumab and Bemcentinib Dose Modifications for Rash 
Rash - onset dming any cycle 
Pembrolizumab 
Bemcentinib 
Grade 1 
No dose modification needed 
No dose modification needed 
Grade 2 
Pembrolizumab can continue as 
Bemcentinib can continue as 
scheduled 
scheduled 
Grade 3 or severe 
Withhold for up to 12 weeks oflast 
Withhold for up to 12 weeks oflast 
dose 
dose. 
•
If resolved to Grade 0 or 1, restart
•
If resolved to Grade 0 or 1,
pembrolizumab
restart at-
•
Permanently discontinue if not
•
If not resolved to Grade 0 or 1,
resolved to Grade 0 or 1, or there is
permanently discontinue or
an inability to reduce corticosteroid
discuss with the medical
to 90 mg (prednisone or
monitor
equivalent) per day 
Grade4 
Permanently discontinue 
Permanently discontinue 
6.6.3.3 
Dose modifications for renal toxicity (renal failure, serum creatinine elevation, 
nephritis) - Table 16 
Table 16: Pembrolizumab and Bemcentinib Dose Modification for Renal Toxicity 
Renal failure, serum ci-eatinine 
elevation, nephritis - onset 
Pembrolizumab 
during any cycle 
Grade 1 
No dose modification needed 
Grade 2 
Withhold for up to 12 weeks oflast 
dose 
•
If resolved to Grade 0 or 1, restart
pembrolizumab
•
Permanently discontinue if not
resolved to Grade 0 or 1, or there
is an inability to reduce
corticosteroid to O10 mg
(prednisone or equivalent) per day 
Grade 3 
Permanently discontinue 
Grade4 
Permanently discontinue 
Bemcentinib 
No dose modification needed 
Withhold for up to 12 weeks oflast 
dose 
•
If resolved to Grade 0 or 1,
restart at-
•
If not resolved to Grade 0 or 1, 
permanently discontinue or 
discuss with the medical
monitor
Withhold for up to 12 weeks oflast 
dose 
•
• 
Ifresolved to Grade 0 or 1
resiil!!!rt at 
and titrate it 
to 
if possible 
If not resolved to Grade 0 or 1, 
permanently discontinue or 
discuss with the medical 
monitor 
Permanently discontinue 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
84 of 126 
C
Confidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
6.6.3.4 
Dose modifications for Increased AST and/or ALT with or without increased 
bilirubin - Table 17 
Table 17: Pembrolizumab and Bemcentinib Dose Modifications for Increased AST and/or 
ALT With or Without Increased Bilirubin 
Please refer to Table 13 and Figure 5 for details on individual actions. 
Increased AST and/or 
ALT with 01· without 
Pembrolizumab 
Bemcentinib 
increased bilirubin 
Grade 1 
No dose modification needed 
No dose modification needed 
Grade 2 
Withhold for up to 12 weeks of 
For 1st occurrence, withhold bemcentinib 
last dose 
for up to 12 weeks 
•
If resolved to Grade 0 or 1, 
•
If improved to Grade 1 or baseline
restart pembrolizumab
within 12 weeks without steroids
•
If not discontinue treatment
restart at-
•
If improved to Grade 1 or baseline
within 12 weeks with steroids, restart
at-
•
If not improved in 12 weeks (with or
without steroids), discontinue or
discuss with the medical monitor
For 2nd occurrence, discontinue or discuss 
with the medical monitor (Please refer to 
Figure 5) 
Grade 3 
Permanently discontinue 
For 1st occurrence, withhold bemcentinib 
for up to 12 weeks and start steroids 
•
If resolved within 12 weeks with or
without steroids restart at-
•
If not improved in 12 weeks (with or
without steroids), discontinue
permanently or discuss with the
medical monitor
For 2nd occurrence, discontinue or discuss 
with the medical monitor (Please refer to 
Figure 5) 
Grade4 
Permanently discontinue 
Permanently discontinue 
6.7 
Blinding and Procedures for Un-blinding the Study 
This is an open-label sh1dy, and there are no blinding/un-blinding procedures. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
85 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
86 of 126 
6.8 
Permitted and Restricted Concomitant Medications 
In general, medications or vaccinations specifically prohibited in the exclusion criteria are not 
allowed during the ongoing trial. Treatment with antacids, proton pump inhibitors and histamine 
receptor 2 inhibitors can be initiated as rescue therapy after patients 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 
trial, discontinuation from trial therapy or vaccination may be required. The investigator should 
discuss any questions regarding this with the Sponsor Clinical Director. The final decision on any 
supportive therapy or vaccination rests with the investigator and/or the patient's primary physician. 
However, the decision to continue the patient on trial therapy or vaccination schedule requires the 
mutual agreement of the investigator, the Sponsor and the patient. 
6.9 
Acceptable Concomitant Medications 
All treatments that the Investigator considers necessary for a patient’s welfare may be administered 
at the discretion of the Investigator in keeping with the community standards of medical care. All 
concomitant medication will be recorded on the CRF including all prescription, over-the-counter, 
herbal supplements, and i.v. medications and fluids. If changes occur during the trial period, 
documentation of drug dosage, frequency, route, and date may also be included on the CRF. 
All concomitant medications received within 30 days before the first dose of trial treatment and 
30 days after the last dose of trial treatment should be recorded. Concomitant medications 
administered after 30 days after the last dose of trial treatment should be recorded for SAEs and 
Events of Clinical Interest (ECIs) as defined in Section 7.4.3.2. 
6.10 
Prohibited Concomitant Medications whilst receiving Pembrolizumab 
Patients are prohibited from receiving the following therapies during the Screening and Treatment 
period (including retreatment for post-complete response relapse) of this trial: 
•
Antineoplastic systemic chemotherapy or biological therapy;
•
Immunotherapy not specified in this protocol;
•
Chemotherapy not specified in this protocol;
•
Investigational agents other than bemcentinib and pembrolizumab;
•
Radiation therapy:
o
Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be
considered on an exceptional case by case basis after consultation with Sponsor.
The patient must have clear measurable disease outside the radiated field.
Administration of palliative radiation therapy will be considered clinical
progression for the purposes of determining PFS. Note: Treatment with
pembrolizumab and bemcentinib must have been discontinued at least one week
prior to radiotherapy and should not be restarted within one week of completing
radiotherapy.
•
Live vaccines within 30 days prior to the first dose of trial treatment and while
participating in the trial. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
87 of 126 
typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed 
virus vaccines and are allowed. However, intranasal influenza vaccines (e.g., Flu - 
Mist®) are live attenuated vaccines, and are not allowed; 
•
Systemic glucocorticoids for any purpose other than to modulate symptoms from an
event of clinical interest of suspected immunologic etiology. The use of physiologic
doses of corticosteroids may be approved after consultation with the Sponsor:
o
Note: Inhaled steroids are allowed for management of asthma.
Patients who, in the assessment by the investigator, require the use of any of the aforementioned 
treatments for clinical management should be removed from the trial. Patients may receive other 
medications that the investigator deems to be medically necessary. 
The Exclusion Criteria describes other medications that are prohibited in this trial. 
There are no prohibited therapies during the Follow Up period once the patient has discontinued 
both treatments. 
6.11 
Supportive Care Guidelines and Rescue Medications for Pembrolizumab 
Patients should receive appropriate supportive care measures as deemed necessary by the treating 
investigator. Suggested supportive care measures for the management of AEs with potential 
immunologic etiology are outlined below. Where appropriate, these guidelines include the use of 
oral or intravenous treatment with corticosteroids as well as additional anti-inflammatory agents 
if symptoms do not improve with administration of corticosteroids.  
Note that several courses of steroid tapering may be necessary as symptoms may worsen when the 
steroid dose is decreased. For each disorder, attempts should be made to rule out other causes such 
as metastatic disease or bacterial or viral infection, which might require additional supportive care. 
The treatment guidelines are intended to be applied when the investigator determines the events to 
be related to pembrolizumab. 
Note: If after the evaluation the event is determined not to be related, the investigator does not 
need to follow the treatment guidance (as outlined below). Refer to Section 6.6 for 
dose modification. 
It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, or skin 
photography as part of evaluation of the event. 
6.12 
Infusion Guidelines for Pembrolizumab 
Signs and symptoms usually develop during or shortly after drug infusion and generally resolve 
completely within 24 hours of completion of infusion.  
Table 18 shows treatment guidelines for patients who experience an infusion reaction associated 
with administration of pembrolizumab. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Table 18: Management of Pembrolizumab-associated Infusion-related Reactions 
NCI CTCAE (v 5.0) Grade 
Treatment 
Premedication at subsequent 
dosing 
Grade 1 
Increase monitoring of vital signs as 
None 
Mild reaction; infusion 
medically indicated until the subject is 
interruption not indicated; 
deemed medically stable in the opinion of 
intervention not indicated 
the investigator. 
Grade 2 
Stop Infusion and monitor symptoms. 
Subject may be premedicated 
Requires infusion interruption but 
Additional appropriate medical therapy 
I .Sh(± 30 minutes) prior to 
responds promptly to 
may include but is not limited to: 
infusion of pembrolizumab 
symptomatic treatment (e.g., 
IV fluids 
(MK-3475) with: 
antihistamines, NSAIDS, 
Antihistamines 
narcotics, IV fluids); prophylactic 
NSAIDS 
Diphenhydramine 50 mg po 
medications indicated for <=24 
Acetaminophen 
(or equivalent dose of 
hrs 
Narcotics 
antihistamine). 
Increase monitoring of vital signs as 
medically indicated until the subject is 
Acetaminophen 500-1000 mg 
deemed medically stable in the opinion of 
po (or equivalent dose of 
the investigator. 
antipyretic). 
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. 
Subjects who develop Grade 2 toxicity 
despite adequate premedication should 
be permanently discontinued from 
further trial treatment administration. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
88 of 126 
C Confidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
NCI CTCAE (v 5.0) Grade 
Grades 3 or4 
Grade 3: 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for other 
clinical sequelae (e.g., renal 
impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor or 
ventilatory support indicated 
Treatment 
Stop Infusion. 
Additional appropriate medical therapy 
may include but is not limited to: 
IV fluids 
Antihistamines 
NSAIDS 
Acetaminophen 
Narcotics 
Oxygen 
Pressors 
Corticosteroids 
Epinephrine 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion of 
the investigator. 
Hospitalization may be indicated. 
Subject is permanently discontinued 
from furthe1· trial treatment 
administntion. 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
Premedication at subsequent 
dosing 
No subsequent dosing 
Appropriate resuscitation equipment should be available in the room and a physician readily available during the 
oeriod of drug administration. 
6.13 
Diet, Activity and Other Considerations 
6.13.1 
Diet 
Patients should maintain a normal diet unless modifications are required to manage an AE such as 
diarrhea, nausea or vomiting. 
6.14 
Contraception 
Pembrolizumab and bemcentinib may have adverse effects on a fetus in utero. Furthermore, it is 
not known if pembrolizumab has transient AEs on the composition of sperm. For this trial, male 
patients will be considered to be of non-reproductive potential if they have azoospemlia (whether 
due to having had a vasectomy or due to an underlying medical condition). 
Female patients will be considered of non-reproductive potential if they are either: 
OR 
OR 
•
postmenopausal (defined as at least 12 months with no menses without an alternative
medical cause; in women <45 years of age a high FSH level in the postmenopausal
range may be used to confum a post-menopausal state in women not using ho1monal
contraception or ho1monal replacement therapy. In the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient.);
•
have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening;
•
has a congenital or acquired condition that prevents childbearing.
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
89 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
90 of 126 
Female and male patients of reproductive potential must agree use highly effective methods of 
contraception while receiving study drug and for 120 days after the last dose of study drug 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
•
Progestogen-only hormonal contraception associated with inhibition of ovulation:
o
Oral
o
Injectable
o
implantable
•
intrauterine device (IUD);
•
intrauterine hormone-releasing system (IUS);
•
bilateral tubal occlusion;
•
vasectomized partner;
•
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 Institutional Review Board (IRB)/Institutional Ethics 
Committee (IECs). Periodic abstinence e.g., calendar, ovulation, sympto-thermal, 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. 
Patients 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. In order to participate in the 
study, patients of childbearing potential must adhere to the contraception requirement (described 
above) from the day of study medication initiation (or 14 days prior to the initiation of study 
medication for oral contraception) throughout the study period up to 120 days after the last dose 
of trial therapy. If there is any question that a patient of childbearing potential will not reliably 
comply with the requirements for contraception, that patient should not be entered into the study. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
91 of 126 
6.14.1 
Use in pregnancy 
If a patient inadvertently becomes pregnant while on treatment with study medication, the patient 
will immediately be removed from the study. The site will contact the patient at least monthly and 
document the patient’s status until the pregnancy has been completed or terminated. The outcome 
of the pregnancy will be reported to the Sponsor without delay and within 24 hours if the outcome 
is a serious adverse experience e.g., death, abortion, congenital anomaly, or other disabling or life-
threatening complication to the mother or new-born. The study Investigator will make every effort 
to obtain permission to follow the outcome of the pregnancy and report the condition of the fetus 
or new-born to the Sponsor. 
6.14.2 
Use in nursing women 
It is unknown whether pembrolizumab is excreted in human milk. Since many drugs are excreted 
in human milk, and because of the potential for serious ARs in the nursing infant, patients who are 
breast-feeding are not eligible for enrolment. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
92 of 126 
7 
ADVERSE EVENTS AND REPORTING REQUIREMENTS 
7.1 
Assessment of Safety 
Progression of the cancer under study is not considered an adverse event unless it is considered to 
be drug-related by the investigator. 
All AEs that occur after the consent form is signed but before treatment allocation 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. 
From the time of treatment allocation through 30 days following cessation of treatment, all 
AEs must be reported by the investigator. Such events will be recorded at each examination on 
the Adverse Event case report forms/worksheets. 
The reporting timeframe for AEs meeting any serious criteria is described in Section 7.4.3. The 
investigator will make every attempt to follow all subjects with non-serious AEs for outcome. 
From the time of treatment allocation through 90 days following cessation of treatment, all 
SAEs (including serious events of special interest) must be reported by the investigator. 
Where a patient has initiated a new cancer treatment, the time period is 30 days after cessation of 
treatment. See Section 7.4.3.1 and Section 7.4.3.2. 
The reporting timeframe for a new pregnancy is described in Section 7.5. 
7.2 
Adverse Event Definition 
An AE is any untoward medical occurrence in a patient or clinical study subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with the product. 
An AE can therefore be any unfavorable or unintended sign, symptom or disease temporally 
associated with the use of the IMP whether or not considered related to the IMP. This includes any 
occurrence that is new, an exacerbation of an existing disease (a worsening of the character, 
frequency or severity of a known condition) or abnormal results of diagnostic procedures, 
including clinically significant laboratory test abnormalities. 
Suggested criteria for the assessment of clinical significance for laboratory abnormalities are as 
follows. 
The laboratory abnormality: 
•
is clearly consistent with the pattern of the patient’s underlying disease or disease
progression;
•
is accompanied by clinical symptoms;
•
requires study drug dose modification or interruption or permanent discontinuation of
study treatment;
•
requires more frequent follow-up assessments, further diagnostic investigation, etc.;
•
requires a change in concomitant medication, therapy, or treatment.
If the clinically significant laboratory abnormality is a sign of a disease or syndrome (e.g., alkaline 
phosphatase and bilirubin 5X ULN associated with cholecystitis), only the diagnosis (e.g., 
cholecystitis) needs to be recorded on the AE CRF. If the clinically significant laboratory 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
93 of 126 
abnormality is not a sign of a disease or syndrome, the abnormality itself should be recorded as an 
AE or SAE on the CRF. If the laboratory abnormality can be characterized by a precise clinical 
term, the clinical term should be recorded as the AE or SAE. For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.” Observations of the same 
clinically significant laboratory abnormality from visit to visit should not be repeatedly recorded 
as AEs or SAEs on the CRF, unless their severity, seriousness, or etiology changes. 
For all AEs, a diagnosis should be recorded on the CRF rather than individual signs and symptoms 
(e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases) wherever possible. However, if a constellation of signs and/or symptoms cannot 
be medically characterized as a single syndrome at the time of reporting, each individual sign 
and/or symptom should be recorded as an AE or SAE on the CRF. If a diagnosis is subsequently 
established, the reported event term should be updated to reflect the medical diagnosis. 
Note that AEs occurring secondary to an initiating event that are separated in time or medically 
significant should be recorded as independent events on the CRF. For example, if a severe 
gastrointestinal hemorrhage leads to a renal failure, both events should be recorded separately on 
the CRF. 
A pre-existing medical condition which is present at the start of the study and described in the 
Medical History CRF, should only be recorded as an AE or SAE if the frequency, severity, or 
character of the condition worsens during the study. When recording such events on the AE CRF, 
it is important to convey the concept that the pre-existing condition has changed by including 
applicable descriptors (e.g., “more frequent headaches”). 
Surgical procedures or other therapeutic interventions themselves are not AEs, but the condition 
for which the surgery/intervention is required is an AE and should be documented accordingly. 
Planned surgical measures and the condition(s) leading to these measures are not AEs, if the 
condition(s) was (were) known before the period of observation and did not worsen during study. 
In the latter case, the condition should be reported as medical history. 
During clinical trials, AEs can be spontaneously reported or elicited during open-ended 
questioning, examination, or evaluation of a patient. To prevent reporting bias, patients should not 
be questioned regarding the specific occurrence of one or more AEs. 
Symptoms and signs of exacerbation or worsening of the patient’s primary disease will not be 
captured as AEs. Progression of the disease under study (i.e., NSCLC) will not be captured as an 
AE unless it is considered to be drug-related by the Investigator. 
7.3 
Importance of Adverse Event Reporting 
Timely and complete reporting of safety information assists BerGenBio in identifying any 
untoward medical occurrence, thereby allowing: 
•
safety of study patients;
•
a greater understanding of the overall safety profile of the investigational drug;
•
recognition of dose-related investigational drug toxicity;
•
appropriate modification of study protocols;
•
improvements in study design or procedures; and
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
94 of 126 
•
adherence to worldwide regulatory requirements.
7.4 
Evaluating Adverse Events
Following the patient’s written consent to participate in the study, AEs occurring after consent, 
but before treatment, and during treatment and within 30 days after cessation of treatment 
are collected in accordance with Section 7.1, Section 7.4.3 and Section 7.5. 
All identified AEs must be accurately recorded and described on the appropriate AE page of the 
eCRF. If known, the diagnosis of the underlying illness or disorder should be recorded, rather than 
its individual symptoms. The following information should be captured for all AEs: date of 
onset and resolution, severity of the event (see definitions in Section 7.4.1), Investigator's opinion 
of the relationship to IMP (see definitions in Section 7.4.2) and assessment whether the event was 
serious or non-serious (see definitions in Section 7.4.3). In addition, treatment required for the 
AE, action taken with IMP, information regarding resolution/outcome. 
7.4.1 
Assessment of severity 
All AEs (including SAEs) are to be accurately recorded on the AE page of the patient’s eCRF. 
Each event will be graded for severity using the classifications of NCI CTCAE v5.0. For events 
not addressed in the NCI CTCAE v5.0, classifications the following grading will apply: 
•
Mild (Grade 1) - Mild; asymptomatic or mild symptoms; clinical or diagnostic
observations only; intervention not indicated.
•
Moderate (Grade 2) - Moderate; minimal, local or non-invasive intervention
indicated; limiting age-appropriate instrumental activity of daily living.
•
Severe (Grade 3) - Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization indicated;
disabling; limiting self-care activity of daily living.
•
Life-threatening (Grade 4) - Life-threatening consequences; urgent
intervention indicated.
•
Death (Grade 5) - Related to adverse event.
7.4.2 
Assessment of relationship
All AEs (including SAEs) will be assessed for the relationship of the AE to both pembrolizumab 
and bemcentinib study drug using the following definitions: 
•
Not/unlikely related - The AE is not related if exposure to the investigational product
has not occurred, OR the occurrence of the AE is not reasonably related in time, OR
the AE is considered unlikely to be related to use of the investigational product because
there are no facts (evidence) or arguments to suggest a causal relationship AND there
is a possible alternative explanation.
•
Possibly related - The administration of the investigational product and AE are
considered reasonably related in time AND the AE could be explained by causes other
than exposure to the investigational product.
•
Probably related - Exposure to the investigational product and AE are reasonably
related in time AND the investigational product is more likely than other causes to be
responsible for the AE OR is the most likely cause of the AE.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
95 of 126 
•
Definitely related - There is a reasonable temporal sequence between exposure to the
investigational product and the AE, OR the event follows a known or expected
response pattern to the investigational product, AND is confirmed by improvement on
stopping the dosage of the investigational product. It may also be confirmed by
reappearance upon repeated exposure where this is medically and ethically acceptable.
The relationship of the study treatment to an AE will be determined by the Investigator and 
subsequently reviewed by the medical monitor. 
For reporting and data analysis purposes, AEs reported with a causality assessment of “Definitely”, 
“Probably”, and “Possibly” are to be considered as “having a reasonable causal relationship” to 
study drug. In case of disagreement between the Investigator and the Sponsor’s medical monitor, 
the more conservative assessment will determine the reportability of the case. 
7.4.3 
Immediate reporting of AEs and events of clinical interest to the Sponsor 
7.4.3.1 
Serious adverse events 
An SAE is any untoward medical occurrence that at any dose (including overdose): 
•
Results in death.
•
Is life-threatening:
o
“Life-threatening” means that the patient was at immediate risk of death at the
time of the SAE; it does not refer to an SAE that hypothetically might have
caused death if it were more severe.
•
Requires hospitalization or prolongation of existing hospitalization:
o
This means that hospital inpatient admission or prolongation of hospital stay
were required for the treatment of the SAE or that they occurred as a
consequence of the event.
o
Visits to a hospital by ambulance or to the emergency room without admission
will not be regarded as hospitalization unless the event fulfils any other of the
serious criteria.
•
Results in persistent or significant disability or incapacity:
o
“Persistent or significant disability or incapacity” means a permanent or
significant and substantial disruption of a person’s ability to carry out normal
life functions.
•
Is a congenital anomaly or birth defect.
•
Is an important medical event:
o
Medical and scientific judgment should be exercised in deciding whether
expedited reporting is appropriate in situations where none of the outcomes
listed above occurred. Important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the
patient or may require intervention to prevent one of the other outcomes listed
in the definition above should also usually be considered serious. Examples of
such events include allergic bronchospasm requiring intensive treatment in an
emergency room or at home, blood dyscrasias, or convulsions that do not result
in inpatient hospitalization, or the development of drug dependency or drug
abuse.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
96 of 126 
Note: In addition to the above criteria, AEs meeting either of the below criteria, although not 
serious per International Council for Harmonisation (ICH) definition, are reportable to the Sponsor 
in the same timeframe as SAEs to meet certain local requirements. 
Therefore, these events are considered serious by the Sponsor for collection purposes. 
•
Is a new cancer (that is not a condition of the study);
•
Is associated with an overdose.
All patients with SAEs must be followed up for outcome. 
For the time period beginning when the consent form is signed until treatment allocation, any SAE, 
or follow up to a SAE, including death due to any cause other than progression of the cancer under 
study, that occurs to any patient must be reported within 24 hours to the Sponsor if it causes the 
patient to be excluded from the trial, or is the result of a protocol-specified intervention, including 
but not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a 
procedure. 
For the time period beginning at treatment allocation through 90 days following cessation of 
treatment, or 30 days following cessation of treatment if the patient initiates new anticancer 
therapy, whichever is earlier, any serious adverse event, or follow up to a SAE, including death 
due to any cause other than progression of the cancer under study, whether or not related to the 
Sponsor's product, must be reported within 24 hours to the Sponsor either by electronic media or 
paper. Electronic reporting procedures can be found in the EDC data entry guidelines. Paper 
reporting procedures can be found in the Investigator Trial File Binder (or equivalent). 
Additionally, any serious adverse event, considered by an investigator who is a qualified physician 
to be related to the Sponsor's product that is brought to the attention of the investigator at any time 
following consent through the end of the specified safety follow-up period specified in the 
paragraph above, or at any time outside of the time period specified in the previous paragraph also 
must be reported immediately to the Sponsor. 
All patients with SAEs must be followed up for outcome. 
7.4.3.2 
Events of clinical interest 
Selected non-serious and SAEs are also known as Events of Clinical Interest (ECI) and must be 
reported to the Sponsor. 
For the time period beginning when the consent form is signed until treatment allocation, any ECI, 
or follow up to an ECI, that occurs to any subject must be reported within 24 hours to the Sponsor 
if it causes the subject to be excluded from the trial or is the result of a protocol-specified 
intervention, including but not limited to washout or discontinuation of usual therapy, diet, placebo 
treatment or a procedure. 
For the time period beginning at treatment allocation through 30 days following cessation of 
treatment, any ECI, or follow up to an ECI, whether or not related to the Sponsor’s product, must 
be reported within 24 hours to the Sponsor, either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting procedures 
can be found in the Investigator Trial File Binder (or equivalent). 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
Events of clinical interest (ECI) for this trial include: 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
1.
an overdose of Sponsor's product ( either pembrolizumab or bemcentinib ), as defined
in Section 7.6, that is not associated with clinical symptoms or abno1mal laborato1y
results.
2.
an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit
of n01mal and an elevated total bilimbin lab value that is greater than or equal to 2X
the upper limit of normal and, at the same time, an alkaline phosphatase lab value that
is less than 2X the upper limit of normal, as determined by way of protocol-specified
laboratory testing or unscheduled laborato1y testing*
*Note: These criteria are based upon available regulatory guidance documents. The purpose of the 
criteria is to specify a threshold of abno1mal hepatic tests that may require an additional evaluation
for an underlying etiology. The trial site guidance for assessment and follow up of these criteria
can be fotmd in the Guidance for Potential Drug-Induced Liver Injury (DILi) Cases Meeting Hy's
Law Criteria held in the Investigator Trial File Binder (or equivalent).
7.4.4 
Reporting SAEs and ECis 
Adverse events classified as SAEs or ECis must be recorded on the designated eCRF page and 
require expeditious handling and reporting to the Drug Safety group at INC to comply with 
regulato1y requirements. 
The Principal Investigator (or designee) will notify INC within 24 hours of identifying an SAE or 
ECI, whether related or um-elated to investigational drug, by completing the SAE form and faxing 
the eCRF pages and any available suppo1ting documentation to INC (see below for contact details). 
When an overdose or diug misuse of either of the investigational products occurs with an adverse 
outcome, the Investigator should only complete the designated AE or SAE eCRF page. 
Expeditious handling and repo1ted may be appropriate. 
In the case of pregnancy, a separate 'pregnancy' and 'pregnancy outcome' form is used. However, 
the patient should be withdi·awn from sh1dy treatment and appropriate follow up agreed with the 
Sponsor. 
Table 19: Contact Details for SAE, ECI, New Cancer and Pregnancy/Lactation Reporting 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
97 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
98 of 126 
7.4.5 
Assessment of Expected Adverse Events 
The Sponsor will assess all SAEs whether they are expected or unexpected. An unexpected AE is 
any adverse drug event considered to be at least possibly related to bemcentinib or pembrolizumab 
where the outcome, specificity, or severity of which is not consistent with those noted in the current 
IB for bemcentinib, or the Summary of Product Characteristics (SmPC) or Prescribing Information 
for pembrolizumab. 
7.5 
Reporting of Pregnancy or Lactation 
Although pregnancy and lactation are not considered AEs, it is the responsibility of investigators 
or their designees to report any pregnancy or lactation in a patient (spontaneously reported to them) 
that occurs during the trial.  
Pregnancies and lactations that occur after the consent form is signed but before treatment 
allocation/randomization must be reported by the investigator if they cause the patient 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.  
Pregnancies and lactations that occur from the time of first dose of study treatment through to 120 
days following cessation of Sponsor’s product, or 30 days following cessation of treatment if the 
patient initiates new anticancer therapy, whichever is earlier, must be reported by the investigator. 
All reported pregnancies must be followed to the completion/termination of the pregnancy. 
Pregnancy outcomes of spontaneous abortion, missed abortion, benign hydatidiform mole, 
blighted ovum, fetal death, intrauterine death, miscarriage, and stillbirth must be reported as 
serious events (as Important Medical Events). If the pregnancy continues to term, the outcome 
(health of infant) must also be reported. 
Pregnancies are to be reported using the same procedures/transmission methods as SAEs: the same 
fax numbers / email address / same SAE cover sheet. A study specific pregnancy for will be 
provided for pregnancy reporting.  
7.6 
Definition of Misuse and Overdose 
Bemcentinib overdose is defined as any dose exceeding the loading dose (
 of bemcentinib. 
For this trial, a pembrolizumab overdose will be defined as ≥1000 mg (5 times the dose) of 
pembrolizumab. No specific information is available on the treatment of overdose of 
pembrolizumab. In the event of overdose, the subject should be observed closely for signs of 
toxicity. Appropriate supportive treatment should be provided if clinically indicated. 
If the pharmacy discovers that an overdose has or may have been administered, they should contact 
the Study Investigator immediately. The Study Investigator will determine if the overdose is 
an Event of Clinical Interest (see Section 7.4.3.2). 
7.7 
Investigational Product Complaints 
Pharmaceutical technical complaints associated with the investigational product must be reported 
to the Sponsor immediately. The same reporting timelines as for SAEs apply. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
99 of 126 
7.8 
Reporting SAEs to the IRB or IEC 
The Investigator must comply with the applicable regulatory requirements related to the reporting 
of SAEs to the IRB or local Institutional Ethics Committee (IEC). All SAEs that are related and 
unexpected must be reported by the Investigator (or alternative responsible person where specified 
in study delegation log) to the IEC/IRBs responsible for the study.  
In such cases, the Drug Safety group will send the Principal Investigator a Council for International 
Organizations of Medical Sciences (CIOMS) or MedWatch form describing the event, for them to 
report to their IEC/IRB. 
Other SAEs (i.e., expected or unrelated SAEs) should be reported per the relevant institution’s 
procedures. 
The Principal Investigator should also comply with the IEC/IRB procedures for reporting any other 
safety information. Where required, submission of Safety Updates by the Principal Investigator to 
Competent Authorities should be handled according to local regulations. The Principal 
Investigator must inform the Sponsor or their designated Clinical Research Organization (CRO) 
regarding these local requirements. Periodically (at least annually), the IB will be updated to 
include new and relevant safety information. 
Until such time that an AE becomes identified in the bemcentinib IB, it should be considered 
unexpected in regard to bemcentinib causality, regardless of whether the AE has been the patient 
of a previous Safety Update. 
7.9 
Follow Up Information on an SAE 
Collection of complete information concerning SAEs is extremely important. Thus, follow-up 
information that becomes available as the SAE evolves, as well as supporting documentation (e.g., 
hospital discharge summaries and autopsy reports), should be collected subsequently, if not 
available at the time of the initial report, and immediately sent using the same procedure as the 
initial SAE report. The original SAE form(s) must be kept on file at the study site. The Sponsor 
will also review SAE reports for missing information and send queries to the site for resolution as 
appropriate. 
Appropriate diagnostic tests should be performed and therapeutic measures, if indicated, should 
be instituted. Appropriate consultation and follow-up evaluations should be carried out by the 
Principal Investigator (or designee). An SAE is followed until it is considered resolved, returns to 
baseline, is chronically ongoing, or is explained by the Principal Investigator.  
7.10 
Sponsor Reporting of SAEs 
The Sponsor is responsible for reporting serious, study drug-related AEs/experiences to the 
Competent Authorities of the countries, the concerned IRBs/IECs participating in the clinical trial 
and the study Investigators. The Sponsor has assigned the drug safety group at INC to act on their 
behalf for safety submissions on this clinical study. 
The Sponsor (or their delegated medical monitor) will determine whether expedited reporting is 
necessary for SAEs depending on the assessment of seriousness, expectedness, and relationship. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
100 of 126 
 
In case of disagreement between the Investigator and the Sponsor’s medical monitor re
Noga
rr
wadi
y ng
causal relationship, the more conservative assessment will determine the reportability of the case. 
The Sponsor, or their delegated CRO, will prepare Development Safety Update Reports (DSUR) 
and send the DSUR to the European Competent Authority(ies) and the US Authority(ies) where 
the trial is approved within the regulatory timeframe appropriate for the outcome 
of their assessment (see Section 7.10.1 and Section 7.10.2). The assigned CRO will send the 
DSUR to the concerned IRB/IECs. 
7.10.1 
Expedited reporting 
The Sponsor (or delegate) is responsible for the ongoing safety evaluation of the IMP. The assigned 
drug safety group is responsible for ensuring that expedited reports are made to all concerned 
Investigators, to the concerned IRB/IECs (where required), and to the relevant regulatory 
authorities of all adverse drug reactions that are both serious and unexpected, and of findings that 
could adversely affect the health of patients, impact on the conduct of the trial, or alter the 
Competent Authority’s authorization to continue the trial. 
In accordance with the US Code of Federal Regulations, Title 21 CFR Part 312.32, the European 
Directive 2001/20/EC, and the ICH Guidelines for Clinical Safety Data Management Definitions 
and Standards for Expedited Reporting, the Sponsor must submit written documentation in the 
form of an Investigational new drug (IND) Safety Report or suspected unexpected serious adverse 
reaction (SUSAR) reports, respectively. The Sponsor should submit to the Regulatory Authority 
all safety updates and periodic reports, as required by applicable regulatory requirements. 
The drug safety group will assign a case number to be used in all future correspondence regarding 
the event. 
All events qualifying as IND Safety Reports/SUSARs will be reported to the relevant regulatory 
authorities, IRB/IECs, and Investigators by the drug safety group. IND Safety Reports/SUSARs 
are required to be reported within 7 calendar days for life-threatening events and those resulting in 
death or 15 calendar days for all others. These timeframes begin with the first notification of the 
IND Safety Reports/SUSARs to the drug safety group from the Investigator. 
7.10.2 
Non-expedited reporting 
All SAEs that do not require expedited reporting will be described in the interim safety reports. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
101 of 126 
8 
DATA EVALUATION: CRITERIA FOR EVALUATION OF OBJECTIVES 
8.1 
Statistical Considerations, Interim Analysis and Sample Size 
The study will employ a k-stage single-arm design, an approach derived from basic statistical 
theory28. For cohort A, if p denotes the true tumor response rate with drug, the null and alternative 
hypotheses to be assessed in this trial are: H0: RR=p0 vs H1: RR=p1 (p0 <p1), with p0=0.15 and 
p1=0.30. To test these hypotheses, this trial is a k-stage single-arm design with k=2, being a 
Simon’s 2-stage design1. In this design with k=2, there are two analyses: a single interim (Stage 1) 
and a final (Stage 2) analysis. At the interim analysis, the response rate is evaluated in a fixed 
number (m) of patients using a predefined decision rule to determine if the study should stop for 
futility. If the study is not stopped for futility, a further fixed number of patients (l) are assessed 
for response, and a final analysis is performed on all (m+l) patients. In both interim and final 
analyses, the response rate will be presented together with the associated exact 90% CI. 
With p0=0.15 and p1=0.30, the interim (Stage 1) analysis will be conducted with m=22 for efficacy 
patients (EE). If 3 or fewer responses are observed in these 22 patients, the cohort will be 
terminated in favor of the null for futility. Otherwise, a further 26 patients may be evaluated, for a 
total of 48 evaluable patients. If a total of 12 or more responses are seen in 48 evaluable patients 
(25%), then the null will have been rejected in favor of the alternative; otherwise, the null will not 
have been rejected.  
Based on 500,000 trial simulations, this design provides an overall power of 80.1% to test the 
stated null and alternative hypothesis with a 1-sided Type I error rate of 0.049. Under the null, the 
probability of correctly stopping for futility at Stage 1 is 57.7%.  
For cohort B and C, if p denotes the true tumor response rate with drug, the null and alternative 
hypotheses to be assessed in these cohorts are: H0: RR=p0 vs H1: RR=p1 (p0 <p1), with p0=0.05 
and p1=0.20. To test these hypotheses, both B and C cohorts are the k-stage single-arm design with 
k=2, being a Simon’s 2-stage design1. In this design with k=2, there are three analyses: an interim 
analysis for Stage 1, an interim analysis for Stage 2 and a final analysis (for both Stage 1 and 
Stage 2). At the interim analysis (Stage 1), the response rate is evaluated in a fixed number (m) of 
patients using a predefined decision rule to determine if the study should stop for futility. If the 
study is not stopped for futility, a further fixed number of patients (l) are assessed for response at 
a second interim analysis (Stage 2). A final analysis is performed on all (m+l) patients at the time 
of study completion – see Section 8.6 for details. For both interim analyses and final analysis, the 
response rate will be presented together with the associated exact 90% CI. 
With p0=0.05 and p1=0.20, the interim (Stage 1) analysis will be conducted with m=13 for efficacy 
patients (EE). If 1 confirmed response is observed before the 13th patient has been followed-up for 
24 weeks a subgroup of the DRC will meet to confirm continuation to Stage 2. If 0 responses are 
observed in these 13 patients, the cohort will be terminated in favor of the null for futility. 
Otherwise, a further 16 patients may be evaluated, for a total of 29 evaluable patients. Once 
16 (EE) evaluable patients have been enrolled in Stage 2, an interim (Stage 2; once all patients 
have been treated and/or followed up for at least 12 months) analysis and a final analysis (at the 
time of study completion – see Section 8.6 for details) will be performed. If a total of 4 or more 
responses (either at Stage 2 interim analysis or at final analysis) are seen in 29 evaluable patients 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
102 of 126 
(13.8%), then the null will have been rejected in favor of the alternative; otherwise, the null will 
not have been rejected.  
Based on 500,000 trial simulations, this design provides an overall power of 80% to test the stated 
null and alternative hypothesis with a 1-sided Type I error rate of 0.05. Under the null, the 
probability of correctly stopping for futility at Stage 1 is 51%. 
8.2 
Data Review Committee 
8.2.1 
Cohort A - Safety Run-In 
Pembrolizumab has not previously been combined with bemcentinib in patients (in any indication) 
and therefore a safety run-in will include a total of 12 patients. 
A Data Review Committee (DRC), consisting of Principal Investigators, the Sponsors’ 
(BerGenBio and Merck) medical monitors, and invited experts as required e.g., statistician, PK or 
PD specialist, will review all patient safety data after 6 patients have been enrolled and followed 
up for 6 weeks (2 cycles) and then again after a further 6 patients (total 12 patients) have had the 
potential for 6 weeks follow-up. At each of these safety reviews, the DRC will consider the rate of 
bemcentinib dose reductions and the rate of permanent discontinuation from bemcentinib and 
pembrolizumab. 
Each patient will have had the potential to receive (as a minimum): 
•
2 cycles of pembrolizumab.
•
Bemcentinib at
 for 3 days, followed by 
 daily for ~6 weeks. 
At the 1st safety run-in (based on 6 patients) the DRC will evaluate the need for dose modification 
for individual patients, or bemcentinib loading or daily dose modification. A rate of >66% (4 or 
more) of patients requiring treatment to be dose reduced (bemcentinib) or permanently 
discontinued (either bemcentinib or pembrolizumab, or both) will considered as a significant rate. 
The 2nd safety run-in (based on the 12 patients) the DRC will again evaluate the need for dose 
modification for individual patients, or bemcentinib loading or daily dose modification. A rate of 
>40% (5 or more) of patients requiring treatment to be dose reduced (bemcentinib) or permanently
discontinued (either bemcentinib or pembrolizumab, or both) will considered as a significant rate.
During the safety run-in reviews, the DRC will have the option to recommend a lower dose of 
bemcentinib (dose level -1) for new patients. Dose level -1 is defined as 
 bemcentinib on 
Days 1, 2 and 3 followed by 
 from Day 4 onwards. 
Additionally, a review of emerging safety data from the whole bemcentinib program will be made 
6 monthly. 
8.2.2 
Cohort A - End of Stage 1 – Efficacy Analysis 
Recruitment for Cohort A will be halted after 22 evaluable patients have been entered, and whilst 
the interim (Stage 1) analysis is conducted. Recruitment will recommence if the decision is made 
to continue to the maximum of 48 (EE) evaluable patients. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
103 of 126 
The DRC will meet to review the overall risk / benefit profile of the combination, together with 
the ORR when 22 patients have been followed up for at least 24 months – and therefore, will have 
data from at least 2 post-treatment tumor assessment scans. The DRC will document the ORR, and 
if it favors the null hypothesis for futility, will recommend if the study should proceed to evaluate 
up to a further 26 patients. This recommendation will take into account the statistically driven 
endpoint, in the context of on-going safety data review of the combination approach, as well as the 
quality of the response e.g., available data on DoR and PFS, where possible. 
Appropriate representatives of the Sponsor and the coordinating personnel may also attend and 
minute DRC meetings. Recommendations of the DRC will be documented and sent to the sites. 
Further details on the composition of the DRC, as well as the process for data review, issue of 
recommendations and decision making, are described in a separate DRC charter for this study. 
8.2.3 
Cohort B – End of Stage 1 – Efficacy Analysis 
In cohort B after 1 response has been confirmed, a subgroup of the DRC will meet to confirm 
continuation to Stage 2 and evaluation of 16 further patients. An interim analysis (Stage 1) will be 
conducted after 13 evaluable patients have at least 1 on-treatment scan. This data will be reviewed 
by the DRC. 
Appropriate representatives of the Sponsor and the coordinating personnel may also attend and 
minute DRC meetings. Recommendations of the DRC will be documented and sent to the sites. 
Further details on the composition of the DRC, as well as the process for data review, issue of 
recommendations and decision making, are described in a separate DRC charter for this study. 
8.2.4 
Cohort C – End of Stage 1 – Efficacy Analysis 
In cohort C after 1 response has been confirmed, a subgroup of the DRC will meet to confirm 
continuation to Stage 2 and evaluation of 16 further patients. An interim analysis (Stage 1) will be 
conducted after 13 evaluable patients have at least 1 on-treatment scan. This data will be reviewed 
by the DRC. 
Appropriate representatives of the Sponsor and the coordinating personnel may also attend and 
minute DRC meetings. Recommendations of the DRC will be documented and sent to the sites. 
Further details on the composition of the DRC, as well as the process for data review, issue of 
recommendations and decision making, are described in a separate DRC charter for this study. 
8.3 
Statistical Analysis Plan 
Detailed statistical analysis information will be provided separately in the Statistical Analysis Plan 
(SAP). The SAP will detail all data handling rules e.g., full definition of patient populations for 
analysis, including the management of missing values and the handling of data for patients lost to 
follow-up or missing other important information. The SAP will also outline protocol deviation 
criteria. Any deviations to the planned analyses specified or populations defined within the SAP 
will be justified in writing and presented within the final clinical study report. It will also describe 
the rules the handling of missing data points for the primary, secondary and exploratory endpoints. 
The SAP will fully describe the efficacy analyses and descriptive summaries that will be 
undertaken for both the interim (Stage 1 and Stage 2) analyses for each cohort, as well as the final 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
104 of 126 
analyses for all cohorts. All efficacy endpoints (ORR, DoR, PFS, DCR, and OS) will be 
summarized and described for both the interims and final analyses for all cohorts (Section 8.12.2). 
Summaries of ORR by PD-L1 and Axl expression will be provided only for the final analyses. 
The clinical database lock for the cohort A final analysis will occur after the final patient in that 
cohort has been followed-up for at least 24 months for disease assessment and after all data are 
reconciled (i.e., “cleaned”) for all patients who participate in this cohort.  
The clinical database lock for the cohort B final analysis will occur after the final patient in that 
cohort has been followed-up for at least 24 months for disease assessment and after all data are 
reconciled (i.e., “cleaned”) for all patients who participate in this cohort.  
The clinical database lock for the cohort C final analysis will occur after the final patient in that 
cohort has been followed-up for at least 24 months for disease assessment and after all data are 
reconciled (i.e., “cleaned”) for all patients who participate in this cohort.  
A single clinical study report (CSR) will be generated. The SAP will be finalized and signed before 
the database lock. An addendum (or addenda) to report SAEs from patients remaining on treatment 
at the time of Last Patient Last Visit (Section 8.6) until study closure will be written. 
The main data analyses intended for this trial are briefly described in this section. The SAP will 
provide full details of all planned data analyses for the primary, secondary and exploratory 
objectives of the study. 
8.4 
Population 
The efficacy objectives will include all evaluable patients (EE) that have received at least one dose 
of bemcentinib and/or pembrolizumab and have measurable disease at entry according to the 
Investigator Site Assessment and who meets the inclusion/exclusion criteria and have at least 
1 on-treatment scan.  
For all safety objectives, the safety set, consisting of all patients (ES) who have received at least 
one dose of bemcentinib and/or pembrolizumab, will be used. 
For some objectives (pharmacokinetics and biomarker) a subgroup of patients of the safety set 
with respective baseline and post-baseline measurements will be used. 
Patients who signed a consent form and were screened but did not receive any treatment will be 
listed if they reported an adverse event in the time after consent and before treatment allocation 
(see Section 7.1). All AEs that occur after the consent form is signed but before treatment 
allocation must be reported if they cause the patient to be excluded from the trial, or are result of 
protocol-specific intervention, including but not limited to, washout or discontinuation of usual 
therapy, diet, placebo treatment or a procedure (Section 7.1) 
8.5 
RECIST 1.1 and Disease Assessment 
Efficacy endpoints in this study, including ORR, DoR, and PFS, will all be based on tumor 
assessment scan evaluation by RECIST 1.12. 
RECIST assessments will be performed using contrast-enhanced CT/MRI assessments of chest, 
abdomen, and pelvis. Additionally, x-ray and bone scans will be used as appropriate. Additional 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
.o 
••• BerGenBio 
•• 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
anatomy should be imaged based on signs and symptoms of individual patients at baseline and 
follow-up. Baseline assessments should be perfo1med no more than 28 days before strut of study 
treatment, and ideally should be perfo1med as close as possible to the sta1t of sh1dy treatment. 
All radiological and non-radiological (e.g., MRI) scans will be reviewed by the local site 
investigator; and if possible, stored electronically (de-identified with the patient's notes) at site. 
A maximum of 5 target lesions, maximum of 2 per organ, must be selected at baseline. All target 
lesions are measurable. Target lesions should be selected on the basis of their size (longest diameter 
for non-nodal lesions or short axis for nodal lesions), but in addition should be those that lend 
themselves to reproducible repeated measurements. 
All remaining lesions present at baseline are considered non tai·get, irrespective of whether they 
are measurable. 
Disease assessments will be perfo1med eve1y 9 weeks ±7 days for the first 46 weeks relative to the 
date of first treatment administration and then eve1y 12 weeks ±7 days thereafter until confomed 
objective disease progression as defined by RECIST 1.12 (iiTespective of the reason for stopping 
treatment or subsequent therapy). 
Any other sites at which new disease is suspected should also be adequately imaged at follow-up. 
If an unscheduled assessment was perfo1med and the patient has not progressed, eve1y attempt 
should be made to perform the subsequent assessments at their scheduled visits. This schedule is 
to be followed in order to ininimize any unintentional bias caused by some patients being assessed 
at a different frequency than other patients. 
Table 20 provides the RECIST 1.12 evaluation and definitions of disease response (based on target 
lesions (TL)): 
Table 20: RECIST 1.1 Evaluation and Definitions of Disease Response 
Complete 
Disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs 
Response (CR) 
must have a reduction in short axis to < 10 mm. 
Putial Response 
At least a 30% decrease in the sum of the diameters ofTLs, taking as reference the baseline 
<PR) 
sum of diameters 
Stable Disease 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD 
(SD) 
Prngression of 
At least a 20% increase in the sum of diameters ofTLs and an absolute increase of at least 
disease (PD) 
5 mm, taking as reference the smallest sum on study (this includes the baseline sum if that is 
the smallest on studv). 
Not Evaluable 
Only relevant if any of the TLs were not assessed or not evaluable or had a lesion 
(NE) 
intervention at this visit. Note: if the sum of diameters meets the progressive disease criteria, 
oro!lI'essive disease overrides not evaluable as a TL resoonse 
The objective response must be confomed by a repeat scan perfo1med at least 4 weeks later. 
Details of any new lesions will also be recorded with the date of assessment. The presence of one 
or more new lesions is assessed as progression, however, in the absence of clinical deterioration, 
treatment can continue. The suspected disease progression should be confirmed after 28 days. 
A lesion identified at a follow up assessment in an anatoinical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 Januaiy 2022 
105 of 126 
C Confidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
The finding of a new lesion should be unequivocal: i.e., not attributable to differences in scanning 
technique, change in imaging modality, or findings thought to represent something other than 
tumor. 
If a new lesion is equivocal, for example because of its small size, the treatment and tumor 
assessments should be continued until the new lesion has been confinned. If repeat scans confinn 
there is a new lesion, then the progression date should be declared using the date of the initial scan. 
Disease progression requires confirmation. The confomato1y scan should occur preferably at the 
next scheduled visit and no earlier than 4 weeks after the initial assessment of progression of 
disease (PD) in the absence of clinical deterioration. 
The overall visit response will be derived using the algorithm shown in Table 21: 
Table 21: Overall Visit Response Algorithm 
Tareet Lesions 
Non-Tareet Lesions 
New Lesions 
Overall Response 
CR 
CR 
Noor NE 
CR 
CR 
NA 
Noor NE 
CR 
CR 
Non-CR/Non-PD 
Noor NE 
PR 
CR 
NE 
Noor NE 
PR 
PR 
Non-PD or NE or NA 
Noor NE 
PR 
SD 
Non-PD or NE or NA 
Noor NE 
SD 
NE 
Non-PD or NE or NA 
Noor NE 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Anv 
Anv 
Yes 
PD 
CR Comp lete response, PR Partial response, SD Stable disease, PD Progression of di sease, NE Not evaluable, NA 
Not ap p licable (only relevant i fthere were no non-target lesions at baseli ne). 
8.5.1 
Immune-related RECIST and confirmation of progression 
RECIST 1.12 will be adapted to accotmt for the unique tumor response characteristics seen with 
treatment of pembrolizumab. lmmtmotherapeutic agents such as pembrolizumab may produce 
antitumor effects by potentiating endogenous cancer-specific immtme responses. The response 
patterns seen with such an approach may extend beyond the typical time course of responses seen 
with cytotoxic agents and can manifest a clinical response after an initial increase in tumor burden 
or even the appearance of new lesions. Standard RECIST may not provide an accurate response 
assessment of immtmotherapeutic agents such as pembrolizumab. Therefore, RECIST 1.12 will be 
used with the following adaptations: 
If radiologic ( or non-radiological) scan suggests that the patient has progressive disease (initial 
PD), tumor assessment should be repeated 2:4 weeks later in order to confom PD with the option 
of continuing treatment per below while awaiting radiologic confirmation of progression. 
•
If repeat scan shows <20% tumor burden compared to nadir, stable or improved
previous new lesion (if identified as cause for initial PD), and stable/improved non­
target disease (if identified as cause for initial PD), treatment may be continued /
resumed.
•
If repeat scan confoms PD due to any of the scenarios listed below, patients will be
discontinued from study therapy.
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
106 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
107 of 126 
In determining whether the tumor burden has increased or decreased, site study team should 
consider all target lesions as well as non-target lesions. 
Scenarios where PD is confirmed at repeat scan: 
•
Tumor burden remains ≥ 20% and at least 5 mm absolute increase compared to nadir;
•
Non-target disease resulting in initial PD is worse (qualitative);
•
New lesion resulting in initial PD is worse (qualitative);
•
Additional new lesion(s) since last evaluation.
In patients who have shown radiological PD, it is at the discretion of the treating physician whether 
to continue a patient on study treatment until a repeat scan is obtained. When feasible, patients 
should not be discontinued from their study treatment until progression is confirmed. When 
clinically stable, patients may continue pembrolizumab beyond RECIST 1.12 progression with 
continued assessment of response. iRECIST reflects that some patients can have a transient tumor 
flare after the start of immunotherapy, but with subsequent disease response. Patients that are 
deemed clinically unstable are not required to have repeat scan for confirmation of progressive 
disease and best medical practice is to be applied. For the purpose of this decision process, lack of 
clinical stability is defined as: 
•
Unacceptable toxicity
•
Clinical signs or symptoms indicating clinically significant disease progression
•
Decline in performance status
•
Rapid disease progression or threat to vital organs or critical anatomical sites (e.g., CNS
metastasis, respiratory failure due to tumor compression, spinal cord compression)
requiring urgent alternative medical intervention.
8.6 
Completion and Closure of the Study 
The study will be completed when either: 
•
The DRC recommends early termination following the review of the ORR and risk-
benefit at
o
the interim (Stage 1) analysis of cohort A or
o
the interim (Stage 1) analysis of cohort B or
o
the interim (Stage 1) analysis of cohort C.
Or 
•
Once all patients have been followed up for at least 24 months (i.e., LPLV) (unless the
patients have died or withdrawn from the study due to other reasons before this time).
At this point, the database lock will occur and final analyses will be performed (study
completion) and the results will be reported in the final CSR.
At the time of study completion there may be patients continuing on study treatment, any 
remaining patients continuing to show benefit from the study treatment will be offered access to 
bemcentinib (e.g., under expanded excess program or roll over study) outside the study, after 
discussion with the sponsor, prior to study closure. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
108 of 126 
For patients ongoing on the study treatment beyond study closure, only limited data will be 
collected. An addendum (or addenda) to the CSRs will be generated to report any outstanding 
safety data. 
Study start is defined by the first patient to enter screening, however, the First Patient In (FPI) is 
when the first patient receives the first dose of study drug. 
Last Patient In (LPI) is the last (EE) evaluable patient enrolled in the study (C1D1). 
LPLV is defined as the last visit of the last evaluable patient (EE) enrolled in the study (i.e., 
when all the enrolled patients have been followed for at least 24 months).  
Study completion is defined by the date of LPLV and includes all data for the final analysis of all 
evaluable patients (EE).  
Study closure is defined by study completion, when all patients have completed their study visits 
and have been withdrawn from the study and the CSR has been produced (excluding any CSR 
addendum for safety data). 
8.7 
Demographic, Medical History, Prior Medication and Other Baseline 
Characteristics 
Demographic characteristics, medical history, prior medication and other baseline data will be 
listed and summarized using descriptive statistics for continuation data and contingency tables for 
categorical data. Prior medication will be summarized by Anatomical Therapeutic Chemical 
(ATC) terms. 
8.8 
Study Treatment 
The number of doses of bemcentinib and pembrolizumab by cycle and over entire study period 
will be listed and summarized using descriptive statistics. The time on study drug until last 
treatment received will be listed and presented by descriptive statistics.  
8.9 
Concomitant Medication 
Concomitant medication and significant non-drug therapies after the start of study treatment will 
be listed and summarized by ATC term in contingency tables. 
8.10 
Reasons for Discontinuation from Study Treatment 
Reasons for discontinuation of study treatment will be listed and summarized. 
8.11 
Primary Objective 
ORR as defined by achieving complete response and/or partial response will be presented by 
percentage rates and 90% CIs. All response assessments will be listed. 
Note that the Disease Assessment time point used for this analysis may vary and need not be the 
first on-treatment assessment. Where there is the possibility of an immune response leading to a 
false categorization of disease progression, results from later tumor assessment scan time points 
may be used for the ORR assessment following the k-stage design. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
109 of 126 
ORR is defined as the percentage of patients with a CR or PR (out of the number of EE patients), 
a 90% CI for the overall ORR will be calculated assuming an exact binomial distribution. 
A patient who has discontinued both treatments, and subsequently responds having received a 
subsequent anti-cancer treatment may be excluded from the subset of responding patients (these 
patients are evaluable though). Such patients will contribute to the time to progression and death 
Kaplan Meier plots. 
Objective response should be confirmed by repeat scan after at least 28 days (at least 4 weeks 
later). 
The ORR will further be explored as follows: 
•
By PD-L1 status, using a Chi square or Fishers Exact Test;
•
By Axl status (+ve or –ve), using a Chi square or Fishers Exact Test; and
•
Summarized in a table of PD-L1 by Axl expression status to explore the ORR in each
of the four quadrants (++, +-, -+, --). That is, patients will be allocated into one of the
4 groupings: where both Axl and PD-L1 are positive; where there is one positive and
one negative and where there are both Axl and PD-L1 negative.
If the PD-L1 expression status is provided as a TPS or in one of 3 possible categories (<1%, 1-49% 
and ≥50%), the patient will be regarded as PD-L1 positive if their TPS is ≥1% 
A patient with Axl positive disease is defined as one with an expression level of 1+ or greater 
according to IHC staining intensity, although other cut offs may be considered. 
For each patient, the best percentage change in tumor volume will be illustrated in a ‘waterfall’ 
plot. 
8.12 
Secondary Objectives 
8.12.1 
Safety 
8.12.1.1 
Adverse events 
Adverse events will be coded as described in Section 8.4. The number of AEs occurring at 
least once in a patient will be listed and summarized by contingency tables for: 
•
primary system organ class, preferred term;
•
preferred term;
•
NCI CTCAE grade;
•
relationship to both study drugs;
•
interruption of study drug;
•
leading to discontinuation;
•
Grade 3 and higher;
•
SAEs;
•
AEs leading to death;
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
110 of 126 
•
standard medical queries
8.12.1.2 
Safety laboratory
Laboratory values will be graded by NCI CTCAE version 5.0, if no grading exists values will be 
classified into low/normal/high based on laboratory normal ranges. Each parameter will be 
presented by descriptive statistics at each visit and change from baseline values at each visit. Shift 
tables for CTCAE grades and normal ranges will be presented. All laboratory values will be listed. 
A separate listing for abnormal lab values (Grade 3 and higher, and low/high values) will be 
presented. 
8.12.1.3 
Vital signs 
Vital signs will be summarized by descriptive statistics at each visit, change from baseline will be 
presented and a listing will be provided. 
8.12.1.4 
Electrocardiogram 
ECG data will be listed overall and a separate listing for any clinically significant finding in ECG 
values will be provided.  
8.12.2 
Efficacy 
8.12.2.1 
Duration of response 
The DoR will only be calculated for patients that have an objective response. The duration of 
response is calculated from the date of the first documented response until the date of progression 
or death; patients who continue to respond at the date of data cut-off (LPLV) will be censored 
using the same date used to censor for the PFS time. Median DoR and respective 95% CIs will be 
presented. 
8.12.2.2 
Disease control rate 
Disease control rate (DCR) is defined as the percentage of patients with a PR, CR or with stable 
disease (out of number EE evaluable). A 95% CI for the DCR will be calculated using an exact 
binomial distribution. 
A Kaplan Meier plot of the duration of response will be presented along with the median duration 
of response. Descriptive statistics will be used as required, including 95% CIs. 
8.12.2.3 
Progression free survival and overall survival 
Kaplan Meier plots of the time to progression and death will be presented, along with the median 
progression free survival (PFS), median overall survival (mOS), and overall survival (OS), as well 
as the estimated survival at 12 months. Descriptive statistics will be used as required, including 
95% CI. 
PFS is measured from the date of the 1st dose of the 1st cycle until the date of progression (the date 
on which the progression is initially observed) or the date of death (whichever is earlier). 
A sensitivity summary of PFS using the first date that a progression is considered (irrespective of 
whether confirmed) will additionally be conducted. Patients who have not progressed or died 
before the date of data cut-off (last patient, last visit) will be censored at their last clinical 
evaluation. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
OS is defined as the time from the date of enrolment tmtil the date of death (from any cause and 
inespective of any subsequent anti-cancer treatment given). Patients who remain known to be alive 
at the date of data cut-off (LPL V) will be censored at their date last known to be alive. The 
estimated stuvival at 12 months will be read from the Kaplan Meier OS curve. Patients who are 
lost to follow-up will be censored at the point last known to be alive; however, if2::2% of patients 
are in this category, a sensitivity sununa1y will be produced to illustrate the overall survival 
assuming the patient died at the date last known in the trial. If possible, the date of death may be 
recovered from publicly available sources such as death registries. 
8.12.3 
Pharmacokinetics 
The analysis plan for PK assessment for bemcentinib in the study will be pa1t of the SAP. 
Pharmacokinetic parameters will be estimated for each patient using a fully validated version of 
WinNonlin Pro (Version 6.3 Phoenix™, Pharsight®), or later version as appropriate. The following
parameters will be derived, where appropriate, from the individual plasma concentration versus 
time profiles. 
Blood samples taken for the purpose of PK assessment of pembrolizumab will be frozen and stored 
in case they are required (e.g., at the request of a regulato1y authority). 
Table 22: Pharmacokinetic Parameters 
Pnameter Definition 
Cmu 
The maximum observed concentration. 
tmu 
The time at Cmu 
AUC0.24b 
The area under the concentration versus time curve from time zero to 24 h post-dose; that is, within 
a dosing interval 
Cav 
Average concentration calculated as AUC0.24h/24 
ti12 
The elimination half-life 
Blood samples taken for the purpose of PK assessment of pembrolizumab will be frozen and stored 
in case they are required in the future (for example, at the request of a regulatory authority). 
8.13 
Exploratory Objectives 
8.13.1 
Biomarker analysis 
The PD-Ll and Axl expression stah1s will be available at the time of the database lock and will 
be utilized in the final analysis of the sh1dy, as described in Section 8.11. 
However, results from other biomarkers (for example, for the assessment of Axl signaling and 
inhibition) and the development of a radiomic signature as a response prognostic biomarker might 
not be available at the time of the data-cut analysis but are intended to be completed before the 
closure of the sh1dy or before the CSR is written at sh1dy completion (whichever is later) - see 
Section 8.6. A separate analysis plan and report (addendum to the CSR) for biomarker analysis 
will be written. All samples will be destroyed 5 years after shldy completion. 
BGBC008 I PN-531- NSCLC Version 11.0 
26 January 2022 
111 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
112 of 126 
9 
QUALITY ASSURANCE 
9.1 
Data Recording 
The Investigator will be responsible for the recording of all data on 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 study monitor (or Clinical Research Associate) 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. 
9.2 
Study Monitoring 
Study monitors will be responsible for the monitoring of the study. 
The study monitor will review the progress of the study on a regular basis to ensure adequate and 
accurate data collections. Monitoring site visits to review the eCRF(s), patient case notes, 
administrative documentation, including the Investigator Site File, and to perform drug 
accountability will be performed throughout the study at appropriate intervals. 
At each study monitoring visit, the Investigator will make available all records pertaining to the 
study. To allow sufficient time to assemble documentation for the Study Monitor, monitoring visits 
will be confirmed in advance of planned visits. 
9.3 
Clinical 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. 
9.4 
Clinical Study Report 
The results of the study will be presented in an integrated Clinical Study Report according to ICH 
guidelines. 
9.5 
Data Retention and Availability 
The Investigator is required to maintain copies of all essential study documentation, including the 
Site Study File, a disc containing all eCRF data (including the full audit trail and all data queries), 
signed informed consent forms, and records for the receipt and disposition of study medications, 
for a specified period required by ICH GCP, or longer if required by local or regulatory authorities. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
113 of 126 
U.S. Federal laws require that an Investigator maintain all study records for the indication under 
investigation for two 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 two years 
after the investigation is discontinued and the FDA is notified. 
European laws require that the Investigator maintain all study records (excluding the patients’ 
medical files) for at least 15 years after completion or discontinuation of the trial, or for at least 
two years after the granting of the last marketing authorization in the European Community (EC) 
and where there are no pending or contemplated marketing applications in the EC, or for at least 
two years after the formal discontinuation of clinical development of the investigational product. 
During the study, the Investigator must make study data accessible to the study monitor(s), the 
Sponsor (or a third-party auditor assigned by the Sponsor), and relevant IEC/IRBs and regulatory 
agencies. The Investigator must ensure the availability of source documents from which the 
information in the eCRF was derived. 
9.6 
Curricula Vitae and Financial Disclosure of Investigators 
All Principal Investigators will be required to provide a current signed and dated curriculum vitae, 
a completed FDA Form 1572 (required in the USA; in the EU, if applicable) and a financial 
disclosure statement (required in the USA; in the EU, if applicable). Sub-investigators may also 
be required to provide a current curriculum vitae and a financial disclosure statement according to 
the regulations of the countries involved. 
9.7 
Protocol Modifications 
No modification of the protocol should be implemented without the prior written approval of the 
Sponsor or the Sponsor’s representative. Any such changes which may affect a patient’s treatment 
or informed consent, especially those increasing potential risks, must receive prior approval by 
the IRB/IEC (Section 10). The exception to this is where modifications are necessary to 
eliminate an immediate hazard to trial patients, or when the change involves only logistical or 
administrative aspects of the trial (e.g., change in monitor, change in telephone number). Other 
administrative revisions which may impact the clinical portion of a study will be duly reported to 
the IRB/IEC by the Principal Investigator. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
114 of 126 
10 ETHICS REVIEW/INFORMED CONSENT AND COMPETENT REGULATORY 
AUTHORITY APPROVAL 
10.1 
Ethical Conduct of the Study 
The study will be conducted in accordance with ICH GCP, the Declaration of Helsinki, the 
European Union Clinical Trials Directive 2001/20/EC, the GCP Directive 2005/28/EC, the 
requirements of local IEC/IRB, and the US Code of Federal Regulations, Title 21 CFR Part 50.  
10.2 
Institutional Review Board or Independent Ethics Committee and Competent 
Regulatory Authority Approvals 
The final study protocol and patient informed consent form will be approved by the appropriate 
IEC/IRB for each investigational site. Approval will be received in writing before initiation of the 
study. 
Changes to the protocol during the trial will be documented as amendments. Depending on the 
contents of the amendment and local legal requirements, the amendment will be submitted for 
approval to the relevant IEC/IRBs and to the relevant competent authorities prior to 
implementation. Exceptions are cases of changes made to protect patient safety, which will be 
implemented immediately. 
If an amendment substantially alters the trial design, increases the potential risk to the patients, 
affects the treatment of the patient, or might otherwise influence the willingness of the patient to 
participate in the trial, then the information sheet must be revised and submitted to the relevant 
IEC/IRB and to the relevant competent authorities, for review and approval. When a patient is 
currently undergoing trial procedures and is affected by the amendment, then the patient must be 
asked to consent again using the new information sheet. 
10.3 
Informed Consent 
The principles of informed consent in the Declaration of Helsinki and GCP guidelines will be 
implemented before any protocol-specific procedures or interventions are carried out. 
All patients will be informed that participation is voluntary and that they can cease their study 
treatment(s) and/or their further participation to any further study assessments at any time without 
necessarily giving a reason and without any penalty or loss of benefits to which they are entitled. 
Patients will be provided with a consent form prior to the commencement of any procedures or 
investigations: 
i.
The Consent to participate in the study will include information about the patient’s disease,
alternative treatment options, the study treatments and their duration, study design and
study assessments and procedures, risks, side effects and potential benefits of
participation. This consent will include:
a.
Consent to provide sufficient tumor tissue to enable Axl kinase and PD-L1
expression measurement by IHC, and an explanation that this includes the
provision of a newly acquired tumor tissue sample.
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
115 of 126 
b. Axl and PD-L1 expression on tumor and infiltrating immune cells measured using
immunohistochemistry and NeoGenomics MultiOmyx will be correlated with
response. Tumor mutational burden and microsatellite instability will be explored.
Whole transcriptome sequencing and serum protein analysis will be performed to
identify gene expression signatures that may identify patients that may respond to
therapy. Serum proteins will be analyzed using the Myriad RBM Discovery/MAP
panel.
c.
Consent that tissue samples taken during the study may be used for additional
biomarker research purposes which may help understand how bemcentinib and
pembrolizumab work in the body and why some patients benefit from the treatment
and others do not.
d. If possible, the electronic storage of all radiological and non-radiological scans at
site for future reference (e.g., medical case studies, publications, and training).
e.
Information regarding the expected (maximum) blood volume to be provided.
f.
Information that treatment with checkpoint inhibitors, such as pembrolizumab, is
occasionally associated with worsening of disease before clinical improvement is
observed. Therefore, their treatment may continue if their doctor suspects that the
patient is benefiting from the treatment.
g. Information that treatment with checkpoint inhibitors, such as pembrolizumab, and
treatment with bemcentinib are associated with side effects and that the patient
must inform the doctor of any side effects, even if the patient does not think they
are important.
h. An explanation that patients will continue to have 12 weekly follow-up visits (or
in some cases, a telephone call) to assess their disease and/or well-being after the
completion of their study treatments. Follow-up visits or telephone contact will
continue until the end of the study.
i.
Information to explain that on-study blood samples will be collected for the
purpose of relevant Axl signaling and inhibition biomarkers and immune profiling
The patient must give consent to participate prior to enrolment in the trial. This consent must be 
given in writing. The Investigator who conducts the informed consent discussion must also sign. 
The Investigator may delegate this responsibility to a suitably qualified member of the study team 
(e.g., Sub-Investigator) if permitted by local regulations. This delegation of responsibility must be 
recorded in the Site Study File. By giving signed consent, the patient will confirm that his or her 
participation is voluntary and that he or she will follow the instructions of the Investigator and 
answer the questions asked. Signatures must be personally dated 
The signed and dated consent form(s) will be kept by the Investigator. Prior to participation in the 
trial, the patient should receive a copy of the signed and dated written informed consent form(s).  
The consent forms must include all elements required by law, local regulations, GCP and ICH 
guidelines including consent to allow the Sponsor, Sponsor representative, or external regulatory 
auditor to review the patient’s medical records. This gives permission to examine, analyze, verify, 
and reproduce any records and reports that are important to the evaluation of the trial.  
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
116 of 126 
10.4 
Patient Participation Card 
A study participation card will be provided to each patient on the trial. The card will indicate that 
he or she is participating in a clinical trial and give the name and contact details of the Sponsor 
and the Investigator/study site. The patient will be asked to retain this card while participating in 
the trial and show it to any other medical practitioners consulted during this time. Patients will be 
advised to contact the Investigator/study site if there are any questions. A sample patient 
participation card is shown in Figure 6. 
Figure 6: Sample Patient Participation Card 
Dear Patient, 
Please inform any physician you are going to 
visit during the course of the study that you are 
participating in a clinical trial by presenting this 
contact card. 
Please carry this card with you at all times until 
the end of the study. 
INSERT NAME is participating in an open-label trial 
of an experimental drug called bemcentinib in 
combination with pembrolizumab in patients with 
lung cancer. 
Study Contact Card 
Clinical Trial: BGBC008 / MK-3475 PN 531 
Eudract Number: 2016-003609-32 
Dear Doctor, 
In the case that additional medications must be 
prescribed to this patient, or you need more 
information about the clinical trial they are 
participating in, or you need to notify the study 
physician about the patient’s worsening 
condition, please contact: 
10.5 
Insurance 
Appropriate insurance for this clinical trial 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 TMF and in the Investigator Site File. 
10.6 
Patient Privacy 
Any party with direct access to patient records or any material which identifies the patient must 
take all reasonable precautions within the constraints of the applicable regulatory requirement(s) 
to maintain the confidentiality of the patients’ identities and Sponsor’s proprietary information.  
In order to maintain patient confidentiality, all CRFs, study reports and communications relating 
to the study will only identify patients by their assigned study number; patients should not be 
identified by name. Depending on the countries involved in the clinical trial, use of patient initials, 
and full date of birth may be prohibited. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
117 of 126 
11 PUBLICATION POLICY 
The original eCRFs and all data generated during the clinical study using the given protocol will 
become the property of the Sponsor. 
Any proposed publication or presentation (including a manuscript, abstract, or poster) for 
submission to a journal or scientific meeting should be sent to the Sponsor for review at least one 
(1) month prior to submission. No single center or groups of centers may publish individually.
Publications arising from this clinical study will include all Investigators as authors. The Sponsor's
comments on the proposed publication shall be considered in good faith by the authors. Sponsor
may delay such submission by a maximum of 90 (ninety) days if it reasonably believes that
publication of results may compromise its intellectual property rights or else insist that such
information or data are removed from the proposed publication. Publication of the results will not
include confidential information without the permission of the Sponsor.
The Sponsor may announce quality assured summary data in order to comply with Financial 
Regulatory Authorities, while ensuring, so far as possible, that such announcements will not 
compromise the Investigators ability to publish the data in appropriate scientific forums. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
12 APPENDIX A: EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
G1·ade ECOG Pl'rformancl' status29 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
0 
Fully active. Able to cany on all pre-disease perfo1mance without restriction. 
1 
Restricted in physically strenuous activity but ambulato1y and able to cany out work 
of a light or sedentary nahrre ( e.g., light housework, office work). 
2 
Ambulatory and capable of all self-care but unable to cany 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 cany on any self-care. Totally confined to bed or chair. 
5 
Dead. 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
118 of 126 
C Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
119 of 126 
13 APPENDIX B: CREATININE CLEARANCE ALGORITHM 
Creatinine clearance should be calculated using the Cockroft-Gault Formula30, which is given 
below: 
US calculation formula: 
CrCl = (140 - Age) x Mass (kilograms) x (0.85 if Female) 
72 x serum Creatinine (mg/dL) 
European calculation formula: 
1.25 x (140 – age) x weight (kg) 
Males:  
    Serum creatinine (µmol/l) 
1.05 x (140 – age) x weight (kg) 
Females:  
Serum creatinine (µmol/l) 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
14 APPENDIX C: THE NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION IN A PATIENT WITH HEART DISEASE 
Overview: The NYHA developed a ftmctional classification for patients with hea1t disease. 
Patients: Heart disease must be present. 
Parameters: 
•
Limitations on physical activity
•
Symptoms (undue fatigue palpitations dyspnea ancVor anginal pain) with ordinary
physical activity
•
Stah1s at rest
Limitations on Physical 
Symptoms with Ordinary Physical 
Status at Rl'st 
Class 
Activity 
Activity 
none 
none 
comfortable 
I 
slight 
symptomatic with ordinary activities 
comfortable 
II 
marked 
symptomatic at less than ordinary 
comfortable 
III 
levels of activity 
unable to perfo1m any 
discomfort with any activity 
symptomatic at 
IV 
activitv 
rest 
From The Criteria Committee of the New York Heart Association. Nomenclarure and Criteria for 
Diagnosis of Diseases of the Hea1t and Great Vessels. (1994). (9th ed.). Boston: Little, Brown & 
Co. 253-256 
BGBC008 I PN-531 -NSCLC Version 11.0 
26 January 2022 
120 of 126 
C Confidential 

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
15 APPENDIX D: DRUGS ASSOCIATED WITH TORSADES DE POINTES 
See example list below. The following website for an updated list of chugs that may cause Torsades 
de Pointes www.AZCERT.org 
Gt'nt'ric Name 
Brand Namt' 
Amiodarone 
Coradone/Pacerone 
Anagrelide 
Amylin®, Xam·id® 
Arsenic trioxide 
Trisenox 
Astemizole 
Hismanal 
Azithromvcin 
Zithromax®, Zmax® 
Bepridil 
Vascor 
Chlorauine 
Arelan 
Chlorpromazine 
Thorazine 
Cisaoride 
Prooulsid 
Citalopram 
Celexa®, Cipramil® 
Clarithromvcin 
Biaxin 
Cocaine 
Cocaine 
Disoovramide 
Noroace 
Dofetilide 
Tikosyn 
Domperidone 
Motilium 
Dronedarone 
Multaq® 
Droperidol 
lnapsine 
faythromvcin 
faythrocin/E.E.S. 
Escitalopram 
Cipralex®, Lexapro® 
Flecainide 
Tambocor®, Almarvtm® 
Halofantrine 
Halfan 
Halooeridol 
Haldol 
Ibutilide 
Covert 
Levomethadvl 
Orlaam 
Mesoridazine 
Serentil 
Methadone 
Methadose/Dolophine 
Moxifloxacin 
Avelox 
Ondansetron 
Zofran®, Anset® 
Petamidine 
NebuPent/Pentam 
Pimozide 
Orap 
Probucol 
Lorelco 
Procainamide 
Pronestyl/Procan 
Ouinidine 
Cardioauin/Ouinaclute 
Sevoflurane 
Ulane®, Soioum® 
Sotalol 
Betaoace 
Sparfloxacin 
Zagam 
Sulpiride 
Dogmatil®, Dolmatil® 
Terfenadine 
Seldane 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
121 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
122 of 126 
Thioridazine 
Mellaril 
Vandetanib 
Zactima 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab 
.o 
••• BerGenBio 
•• 
BGBC00S/MK-3475 PN-531 
Version 1.0 Final 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
16 APPENDIX E: LOCAL LABORATORY PARAMETERS 
Clinical Chemistry 
Hematology, including Coagulation 
Calcium 
Red cell count, mean corpuscular volume 
Total protein 
Hemoglobin 
Albumin 
Absolute reticulocyte cotmt 
Total bilimbin 
Platelet count 
Alanine transaminase (ALT, SGPTI 
White blood cells 
Aspa1tate transaminase (AST, SGOT) 
Leucocvte differential cotmt (% & absolute) 
Lactate dehydrogenase (LDH) 
International n01malized ratio or prothrombin time 
Alkaline phosphatase 
Activated partial thromboplastin time 
Glucose (random) 
Urinalysis 
Sodium 
Glucose 
Potassium 
Protein 
Bicarbonate 
Bilirubin 
Chloride 
Ketones 
Magnesium 
Blood 
Urea = Blood urea nitrogen 
PH 
Creatinine 
Specific gravity 
Phosphate 
Microscopic examination when indicated 
Amylase 
FSH (female menopausal patients; at Screening 
TSH, Free T4, T3, Free T3 
HCG (female pre-menopausal patients; at Screenin2) 
BGBC008 I PN-531 - NSCLC Version 11.0 
26 January 2022 
123 of 126 
C
Confidential 

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
124 of 126 
17 REFERENCES 
1  
Simon R. Optimal Two-Stage Designs for Phase II Clinical Trials. Controlled Clinical 
Trial; 10:1-10, 1989.  
2  
Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumors: revised RECIST guideline (version 1.1). Eur J Cancer; 45(2):228-47, 2009. 
3  
Fossella FV et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide 
in patients with advanced non-small-cell lung cancer previously treated with platinum-
containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study 
Group. J Clin Oncol;18(12):2354-62, 2000. 
4  
Fossella FV et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide 
in patients with advanced non-small-cell lung cancer previously treated with platinum-
containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study 
Group. J Clin Oncol;18(12):2354-62, 2000 
5  
GLOBOCAN 2008: Estimated cancer Incidence, Mortality, Prevalence and Disability- 
adjusted life years (DALYs) Worldwide in 2008. Available from URL: 
http://globocan.iarc.fr/factsheets/cancers/lung.asp. Accessed 29 October 2013. 
6  
Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin 61:69-90, 
2011. 
7 
Cetin K, Ettinger DS et al. Survival by histologic subtype in stage IV NSCLC based on 
data from the Surveillance, Epidermiology and End Results Program. Clin. Epidemiol; 3 
139-148, 2011.
8  
Nagata K, Ohashi K, Nakano T, et al: Identification of the product of growth arrest-specific 
gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem 
271:30022-7, 1996. 
9  
Linger RM, Keating AK, Earp HS, et al: TAM receptor tyrosine kinases: biologic 
functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res 
100:35-83, 2008. 
10  
Angelillo-Scherrer A, Burnier L, Lambrechts D, et al: Role of Gas6 in erythropoiesis and 
anemia in mice. J Clin Invest 118:583-96, 2008. 
11  
Behrens EM, Gadue P, Gong SY, et al: The mer receptor tyrosine kinase: expression and 
function suggest a role in innate immunity. Eur J Immunol 33:2160-7, 2003. 
12  
Caraux A, Lu Q, Fernandez N, et al: Natural killer cell differentiation driven by Tyro3 
receptor tyrosine kinases. Nat Immunol 7:747-54, 2006. 
13  
Wu YM, Robinson DR, Kung HJ: Signal pathways in up-regulation of chemokines by 
tyrosine kinase MER/NYK in prostate cancer cells. Cancer Res 64:7311-20, 2004. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
125 of 126 
14  
Holland SJ, Pan A, Franci C, et al: R428, a selective small molecule inhibitor of Axl 
kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. 
Cancer Res 70:1544-54, 2010. 
15  
Mudduluru G, Vajkoczy P, Allgayer H: Myeloid zinc finger 1 induces migration, invasion, 
and in vivo metastasis through Axl gene expression in solid cancer. Mol Cancer Res 8:159-
69, 2010. 
16  
Shieh YS, Lai CY, Kao YR, et al: Expression of axl in lung adenocarcinoma and 
correlation with tumor progression. Neoplasia 7:1058-64, 2005. 
17  
Wimmel A, Glitz D, Kraus A, et al: Axl receptor tyrosine kinase expression in human lung 
cancer cell lines correlates with cellular adhesion. Eur J Cancer 37:2264-74, 2001. 
18  
Rikova K, Guo A, Zeng Q, et al: Global survey of phosphotyrosine signaling identifies 
oncogenic kinases in lung cancer. Cell 131:1190-203, 2007. 
19  
Stommel JM, Kimmelman AC, Ying H, et al: Coactivation of receptor tyrosine kinases 
affects the response of tumor cells to targeted therapies. Science 318:287-90, 2007. 
20  
Zhang Z, Lee JC, Lin L, et al: Activation of the AXL kinase causes resistance to EGFR-
targeted therapy in lung cancer. Nat Genet 44:852-60, 2012. 
21  
Liu L, Greger J, Shi H, et al: Novel mechanism of lapatinib resistance in HER2-positive 
breast tumor cells: activation of AXL. Cancer Res 69:6871-8, 2009. 
22  
Hector A, Montgomery EA, Karikari C, et al: The Axl receptor tyrosine kinase is an 
adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer 
Biol Ther 10:1009-18, 2010. 
23  
Asiedu MK, Beauchamp-Perez FD, Ingle JN, et al: AXL induces epithelial-to-
mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene 
33:1316-24, 2014. 
24  
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev 
Immunol; 22, 329-60, 2004 
25  
Zou W, Chen L. Inhibitory B7-family molecules in the tumor microenvironment. Nat Rev 
Immunol; 8(6), 467-77, 2004 
26  
Lou Y et al, Epithelial-mesenchymal transition is associated with a distinct tumor 
microenvironment including elevation of inflammatory signals and multiple immune 
checkpoints in lung adenocarcinoma. Clinical Cancer Res 22(15) July 15, 2016 
27 
Hugo Wet al, Genomic and transcriptomic features of response to Anti-PD-1 therapy in 
metastatic melanoma. Cell 165(1): 35–44; 2016. 
28  
Tan and Xiong, A flexible multi-stage design for phase II oncology trials. Pharm Stat;. 
10(4):369-73, 2011. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final

BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen 
Norway 
BGBC008 / PN-531 – NSCLC Version 11.0 
26 January 2022 
126 of 126 
29  
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am. J. Clin. Oncol; 5(6):649-55, 1982. 
30  
Cockcroft D, Gault MD. Prediction of creatinine clearance from serum creatinine. Nephron; 
16:31-41, 1976. 
___________
 
____________________________________________________________________________________
BerGenBio ASA 
bemcentinib (BGB324); pembrolizumab
BGBC008/MK-3475 PN-531 
Version 1.0 Final