Clinical trial NCT06469138
Conditions: Non-Small Cell Lung Cancer Metastatic Melanoma Acute Myeloid Leukemia Myelodysplastic Syndromes Metastatic Pancreatic Cancer Glioblastoma Malignant Mesothelioma COVID-19
Sponsor: BerGenBio ASA
Start date: 2022-08-02; Completion date: 2022-09-23
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The aims of this Study were to determine:

* How much of the Study Drug (bemcentinib) ends up in urine and faeces
* How much of the Study Drug and its breakdown products get into the bloodstream
* The breakdown products (metabolites) of the Study Drug
* The safety of the Study Drug and any side effects that might be associated with it.

Detailed description:
This was a Phase 1, open-label, nonrandomized, single oral dose study in up to 8 healthy male subjects (with 6 required to complete the study).

Potential subjects were screened to assess their eligibility to enter the study within 28 days prior to dose administration. Up to 8 subjects were enrolled to ensure that 6 subjects completed the study. Subjects were admitted into the study site on Day -1. On the morning of Day 1, all subjects received a single oral dose of 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib, 30 minutes after starting a standard high-fat breakfast.

Subjects were confined to the study site until at least Day 8. Subjects were discharged from the study site on Day 8 if the following discharge criteria were met:

·≥90% mass balance recovery, and

·\<1% of the total radioactive dose is recovered in combined excreta (urine and feces)in 2 consecutive 24-hour periods.

If these discharge criteria were not met by Day 8, subjects were required to remain resident until discharge criteria are met, up to Day 15. If criteria were not met by Day 15, subjects were asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential basis to allow extrapolation of urinary and fecal excretion. If needed, the 2 additional 24-hour nonresidential collections started on the morning of Days 22 and 29 (to be brought into the study site at the end of the collection interval on Days 23 and 30, respectively). If on the second occasion the subject still did not meet the desired criterion, then the subject was discharged from the study, per investigator and sponsor decision.

Subjects experiencing emesis during the first 4 hours post-dose were discharged on the same day from the study site, provided there were no safety concerns, and after discharge study procedures were performed.

The total duration of study participation for each subject (from screening to outpatient visit \[if required\]) was anticipated to be a maximum of approximately 58 days.

Arms: arm 1: This is the only treatment arm in this study. Up to 8 participants will receive a single oral dose of 200 mg containing approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib, 30 minutes after starting a standard high-fat breakfast.
Interventions: intervention 1: Bemcentinib
Intervention descriptions: intervention 1: Each 200 mg dose contains approximately 32.8 μCi (1.21 MBq) of 14C-bemcentinib and is administered as a single dose on Day 1 of the study.

Protocol documents:
Prot_SAP_000.pdf: 
 
Protocol 
A Phase 1, Open-label, Nonrandomized Study to Investigate the Mass 
Balance Recovery and Metabolic Profile of 14C-bemcentinib Following 
Single Oral Administration in Healthy Male Subjects 
 
 
Protocol Status: Final 
Protocol Version: 2.0 
Protocol Date: 10 May 2022 
Replaces: Protocol Version 1 – 21 December 2021 
Investigational Medicinal Product: Bemcentinib, formerly known as BGB324 
Protocol Reference: BGBC021 
Labcorp Drug Development Study: 8479217 
EudraCT Number: 2021‐005631‐24 
 
 
Sponsor: 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen, Norway 
Study Site: 
Labcorp Clinical Research Unit Ltd. 
Springfield House 
Hyde Street 
Leeds, LS2 9LH 
UK 
 
 
 
Sponsor Signatory: 
 
 
Principal Investigator: 
 
 
 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


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SPONSOR APPROVAL 
 
I have read the protocol and approve it. 
 
 
 
 
 
 
Electronically signed below 
13 May 2022 
 
 
 
 
Date 
 
 


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INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
 
 
 
 
 
Electronically signed below on behalf 
of 
 
13 May 2022 
 
 
 
 
Date 
 


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STUDY IDENTIFICATION 
 
Sponsor 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen, Norway 
Sponsor’s Study Contact 
 
 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen, Norway 
Sponsor’s Medical Contact 
 
 
BerGenBio ASA 
Jonas Lies vei 91 
5009 Bergen, Norway 
 
Study Site 
Labcorp Clinical Research Unit Ltd. 
Springfield House 
Hyde Street 
Leeds, LS2 9LH 
UK 
Principal Investigator/ Project 
Physician 
 
 
Labcorp Clinical Research Unit Ltd. 
Springfield House 
Hyde Street 
Leeds, LS2 9LH 
UK 
 
 
 
Clinical Laboratory 
Labcorp Early Development Laboratories Ltd. 
Otley Road 
Harrogate, HG3 1PY 
UK 
Bioanalytical, Radioanalytical, 
and Metabolite Profiling and 
Identification Laboratory 
Labcorp Early Development Laboratories Ltd. 
Otley Road 
Harrogate, HG3 1PY 
UK 
 
 
Statistician 
 
Labcorp Drug Development 


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Protocol Amendment Summary of Changes 
The following key changes have been made in Protocol Version 2.0: 
 
Section 
Revision Description 
General 
The Principal Investigator was updated. 
The radiolabeled dose was corrected to 32.8 µCi (1.21 MBq) 
throughout the protocol. 
The discharge criteria were updated to remove plasma 
radioactivity levels below the limit of quantitation for 2 
consecutive collections. 
Editorial, formatting, and consistency updates throughout. 
Amendments to abbreviations list to align with text. 
Version 16 of the Investigator’s Brochure was added to reference 
section. 
Section 1.2 Summary of 
Nonclinical Pharmacokinetics 
Updated in line with Version 16 of the Investigator’s Brochure. 
Section 1.3 Summary of 
Clinical Experience 
Updated in line with Version 16 of the Investigator’s Brochure. 
Section 3.3 Selection of Doses 
in the Study 
Updated to correct committed effective radiation dose of 0.997 
mSv. 
Appendix 4: Contraception 
Guidance 
Updated to allow for the reduction in duration of contraception 
from 120 days to 90 days based on new available data within 
Version 16 of the Investigator’s Brochure. 
Clarification was included to highlight vasectomy applied to 
male subjects. 


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SYNOPSIS 
Study Title 
A Phase 1, open-label, nonrandomized study to investigate the mass balance recovery and 
metabolic profile of 14C-bemcentinib following single oral administration in healthy male 
subjects. 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary: 
• 
to determine the mass balance recovery (urine 
and feces) and route and rate of elimination of 
14C-bemcentinib 
• 
to determine the PK of total radioactivity in 
plasma and whole blood and of bemcentinib in 
plasma after a single oral dose of 
14C-bemcentinib in healthy male subjects. 
• 
total radioactivity recovery (fet1-t2) in 
urine and feces 
• 
PK parameters including, but not limited 
to, AUC0-∞, AUC0-tlast, Cmax, tmax, and t1/2 
for bemcentinib in plasma and total 
radioactivity in plasma and whole blood 
and urinary recovery of bemcentinib 
(fet1-t2). 
Secondary: 
• 
to determine the metabolite profile of 
14C-bemcentinib in plasma, urine, and feces 
• 
to identify the chemical structure of the major* 
metabolites of bemcentinib 
*based on the MIST guidelines: >10% of 
bemcentinib parent exposure in plasma after 
oral administration 
• 
to assess safety and tolerability of 
14C-bemcentinib when administered to healthy 
subjects. 
• 
quantitative metabolic profiles of 
bemcentinib in plasma and excreta 
• 
identification of bemcentinib major 
metabolites in plasma (>10% relative 
total drug related exposure) and excreta 
(>10% of excreted dose) 
• 
incidence and severity of AEs 
• 
incidence of laboratory abnormalities, 
based on hematology, clinical chemistry, 
and urinalysis test results 
• 
12-lead ECG parameters 
• 
vital signs measurements 
• 
physical examinations. 
Abbreviations: AE = adverse event; AUC0-∞ = area under the concentration-time curve from time 0 extrapolated to infinity; 
AUC0-tlast = area under the concentration-time curve from time 0 to the time of the last quantifiable concentration; 
Cmax = maximum observed concentration; ECG = electrocardiogram; fet1-t2 = percentage of the dose administered recovered 
over the time interval t1 to t2; MIST = Metabolites in Safety Testing; PK = pharmacokinetics; t1/2 = apparent terminal 
elimination half-life; tmax = time of the maximum observed concentration. 
 
Study Design 
This will be a Phase 1, open-label, nonrandomized, single oral dose study in healthy male 
subjects. 
Potential subjects will be screened to assess their eligibility to enter the study within 28 days 
prior to dose administration. Subjects will be admitted into the study site on Day -1 and be 
confined to the study site until at least Day 8. On Day 1, subjects will receive a single oral 
dose of 14C-bemcentinib. Subjects will be discharged if the following discharge criteria are 


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met: ≥90% mass balance recovery and <1% of the total radioactive dose is recovered in 
combined excreta (urine and feces) in 2 consecutive 24-hour periods. 
If these discharge criteria are not met by Day 8, subjects will be required to remain resident 
until discharge criteria are met, up to Day 15. If criteria are not met by Day 15, subjects may 
be asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential 
basis to allow extrapolation of urinary and fecal excretion. If needed, the 2 additional 24-hour 
nonresidential collections will start on the morning of Days 22 and 29 (to be brought into the 
study site at the end of the collection interval on Days 23 and 30, respectively). If on the 
second occasion the subject has still not met the desired criterion, then the subject will be 
discharged from the study, per investigator and sponsor decision. 
Number of Subjects 
Up to 8 subjects will be enrolled and studied as a single group in order that 6 subjects 
complete the study. 
Diagnosis and Main Criteria for Inclusion 
Healthy male subjects aged between 35 and 55 years (inclusive) with a body mass index 
between 18.0 and 32.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
Each subject will receive a single oral dose of 
 mg of 14C-bemcentinib as two 
-mg 
capsules containing approximately 
 μCi (
 MBq) on the morning of Day 1, 
30 minutes after starting a standard high-fat breakfast. 
Duration of Subject Participation in the Study 
Planned screening duration: approximately 4 weeks. 
Planned study duration (screening to outpatient visit [if required]): a maximum of 
approximately 9 weeks. 
Statistical Methods 
Pharmacokinetic parameters will be derived by standard noncompartmental analysis. 
Pharmacokinetic and safety parameters will be listed and summarized. No formal statistical 
analysis will be performed. 


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TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................ 1 
SPONSOR APPROVAL ........................................................................................................... 2 
INVESTIGATOR AGREEMENT ............................................................................................ 3 
STUDY IDENTIFICATION ..................................................................................................... 4 
PROTOCOL AMENDMENT SUMMARY OF CHANGES .................................................... 5 
SYNOPSIS ................................................................................................................................ 6 
TABLE OF CONTENTS .......................................................................................................... 8 
LIST OF TABLES .................................................................................................................. 10 
LIST OF ABBREVIATIONS ..................................................................................................11 
1. 
INTRODUCTION ........................................................................................................... 12 
1.1. 
Overview ............................................................................................................... 12 
1.2. 
Summary of Nonclinical Pharmacokinetics .......................................................... 12 
1.3. 
Summary of Clinical Experience .......................................................................... 14 
1.4. 
Study Rationale ..................................................................................................... 15 
1.5. 
Benefit-risk Assessment ........................................................................................ 15 
2. 
OBJECTIVES AND ENDPOINTS ................................................................................. 15 
3. 
INVESTIGATIONAL PLAN ......................................................................................... 16 
3.1. 
Overall Study Design and Plan ............................................................................. 16 
3.2. 
Discussion of Study Design .................................................................................. 17 
3.3. 
Selection of Doses in the Study ............................................................................ 18 
4. 
SELECTION OF STUDY POPULATION ..................................................................... 18 
4.1. 
Inclusion Criteria ................................................................................................... 18 
4.2. 
Exclusion Criteria .................................................................................................. 19 
4.3. 
Subject Number and Identification ........................................................................ 20 
4.4. 
Subject Withdrawal and Replacement .................................................................. 21 
4.5. 
Study Termination ................................................................................................. 21 
5. 
STUDY TREATMENTS ................................................................................................ 21 
5.1. 
Description, Storage, Packaging, and Labeling .....................................................21 
5.2. 
Study Treatment Administration ........................................................................... 22 
5.3. 
Randomization....................................................................................................... 22 
5.4. 
Blinding ................................................................................................................. 22 
5.5. 
Treatment Compliance .......................................................................................... 23 
5.6. 
Drug Accountability ...............................................................................................23 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................ 23 
6.1. 
Concomitant Therapies ......................................................................................... 23 
6.2. 
Diet ........................................................................................................................ 23 
6.3. 
Smoking ................................................................................................................ 24 
6.4. 
Exercise ................................................................................................................. 24 


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6.5. 
Blood Donation ..................................................................................................... 24 
7. 
STUDY ASSESSMENTS AND PROCEDURES .......................................................... 25 
7.1. 
Pharmacokinetic Assessments ............................................................................... 25 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing .........................25 
7.1.2. 
Pharmacokinetic, Total Radioactivity, and Metabolite Urine and Feces 
Collection and Processing ........................................................................... 25 
7.1.3. 
Vomitus Sample Collection ........................................................................ 26 
7.1.4. 
Analytical Methodology ...............................................................................26 
7.2. 
Safety and Tolerability Assessments ..................................................................... 26 
7.2.1. 
Adverse Events .............................................................................................26 
7.2.2. 
Clinical Laboratory Evaluations .................................................................. 26 
7.2.3. 
Vital Signs ................................................................................................... 27 
7.2.4. 
12-Lead Electrocardiogram ......................................................................... 27 
7.2.5. 
Physical Examination .................................................................................. 27 
8. 
SAMPLE SIZE AND DATA ANALYSIS ..................................................................... 27 
8.1. 
Determination of Sample Size ............................................................................... 27 
8.2. 
Analysis Populations ............................................................................................. 28 
8.2.1. 
Safety Population .........................................................................................28 
8.2.2. 
Pharmacokinetic Population .........................................................................28 
8.2.3. 
All Subjects Population ............................................................................... 28 
8.3. 
Pharmacokinetic Analyses .....................................................................................28 
8.4. 
Safety Analysis ...................................................................................................... 28 
8.5. 
Interim Analysis .................................................................................................... 28 
9. 
REFERENCES ................................................................................................................ 28 
10. APPENDICES ................................................................................................................. 30 
Appendix 1: Adverse Event Reporting ..............................................................................31 
Appendix 2: Clinical Laboratory Evaluations ....................................................................34 
Appendix 3: Total Blood Volume ......................................................................................35 
Appendix 4: Contraception Guidance ................................................................................36 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................38 
Appendix 6: Schedule of Assessments ...............................................................................41 


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LIST OF TABLES 
Table 1: Objectives and Endpoints .....................................................................................16 
Table 2: High-fat Breakfast Content ................................................................................. 24 
Table 3: Pharmacokinetic Assessments ............................................................................. 25 


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LIST OF ABBREVIATIONS 
AE 
adverse event 
ALARA 
as low as (is) reasonably achievable 
API 
active pharmaceutical ingredient 
AUC 
area under the plasma concentration-time curve 
AUC0-∞ 
area under the plasma concentration-time curve from time 0 
extrapolated to infinity 
AUC0-tlast 
area under the plasma concentration-time curve from time 0 to the time 
of the last quantifiable concentration 
CSR 
clinical study report 
Cmax 
maximum observed plasma concentration 
COVID-19 
coronavirus disease 2019 
CRO 
contract research organization 
CYP 
cytochrome P450 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICRP 
International Commission on Radiological Protection 
IFN 
interferon 
IMP 
investigational medicinal product 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic 
SAE 
serious adverse event 
t½ 
apparent plasma terminal elimination half-life 
tmax 
time of the maximum observed plasma concentration 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Overview 
Bemcentinib, formerly known as BGB324 and R428, is being developed for the treatment of 
a range of solid tumors and myeloid malignancies, as well as SARS-CoV-2 infection 
(COVID-19). BerGenBio ASA (BerGenBio)-sponsored and investigator-led studies are 
ongoing in patients with non-small cell lung cancer, metastatic melanoma, acute myeloid 
leukemia (AML), myelodysplastic syndrome, metastatic pancreatic cancer, glioblastoma, 
malignant mesothelioma, and COVID-19. Bemcentinib is being administered in various 
studies as monotherapy and in combination with erlotinib, cytarabine, decitabine, 
pembrolizumab, docetaxel, cisplatin, nab-paclitaxel, gemcitabine, and dabrafenib/trametinib. 
In previous and ongoing studies bemcentinib is taken orally, initiated at a dose of 400 mg 
once daily for a 3-day loading period, followed by a maintenance dose of 200 mg daily. 
Bemcentinib is a small molecule AXL kinase inhibitor which has demonstrated potent and 
selective inhibition of AXL in biochemical and cell-based kinase inhibition assays. In the 
oncology setting bemcentinib has been shown in vitro to inhibit cell proliferation in a number 
of different cell lines and induce apoptosis and cell death in acute myeloid leukemia cell 
lines. Bemcentinib showed pharmacological efficacy as a single agent and in combination 
with targeted chemo- or immune-checkpoint inhibitors in vivo in a variety of hematologic 
and primary and metastatic solid tumor models. As a single agent, bemcentinib inhibited 
tumor growth and prolonged survival in human acute myeloid leukemia xenograft models 
and syngeneic bone marrow transplantation mouse models and affected the expansion and 
survival of myelodysplastic cells. AXL is a recognized therapeutic target for the treatment of 
cancer and is an important negative regulator of type I interferon (IFN) responses that are 
important for both anti-cancer treatments and cellular anti-viral responses. 
The AXL pathway is a mechanism utilized by several enveloped viruses to enter host cells 
and dampen viral immune response. The AXL receptor mediates entry of enveloped viruses 
such as Zika and Ebola through “apoptotic mimicry”. Phosphatidylserine on the viral 
envelope is tethered to AXL by its bound ligand, growth arrest-specific 6, leading to virus 
internalization. Viruses also activate AXL signal transduction that dampens key anti-viral 
type I IFN responses. Preclinical data show that AXL-mediated internalization and Type 1 
IFN suppression extend to SARS-CoV-2 and that bemcentinib acts on 2 host pathways to 
inhibit coronavirus replication, namely prevention of viral entry and enhanced anti-viral IFN 
response. 
1.2. 
Summary of Nonclinical Pharmacokinetics 
Nonclinical repeat dose toxicity studies were performed using daily oral gavage doses of 
bemcentinib administered to mice, rats, dogs, and monkeys. For oral administration, 
bemcentinib was prepared as a suspension in 0.5% (weight/volume [w/v]) hydroxypropyl 


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methyl cellulose in 0.15% (w/v) polysorbate 80, unless otherwise stated. Bemcentinib was 
not well tolerated in dogs due to significant gastrointestinal toxicity. Based upon the high 
plasma exposure and reasonable tolerability to bemcentinib in range-finding studies, mice 
and monkeys were selected for repeat dose Good Laboratory Practice (GLP) toxicity studies. 
Single doses of bemcentinib were administered to male and female Sprague Dawley rats to 
identify the maximum tolerated dose. Bemcentinib was administered by oral gavage at doses 
of 100, 200, 600, and 1000 mg/kg (equivalent to 600, 1200, 3600, and 6000 mg/m2) to 
3 rats/sex/group. All animals survived until scheduled euthanasia. Minimal 
bemcentinib-related changes were identified, with no bemcentinib-related effects identified as 
gross findings. 
Repeat dose studies with bemcentinib were conducted in mice, rats, dogs, and monkeys. 
Bemcentinib was administered orally once daily for 10 days (rats and dogs) in non-GLP 
studies and for 28 days in GLP studies in mice and monkeys. Once and twice daily dosing for 
a total of 9 days was also investigated in a non-GLP monkey study. In the 28-day GLP 
studies, the treatment period was followed by a treatment-free recovery period of 14 or 
16 days, in monkeys and mice respectively, in order to assess the reversibility of any 
treatment-related effects and for evidence of delayed toxicity. Initial toxicology work was 
conducted in line with International Council for Harmonisation S9 guidelines to support the 
initial oncology. Additionally, a 26-week GLP study was also conducted in the mouse along 
with a 39-week GLP study conducted in monkeys. 
Pharmacokinetic (PK) studies were conducted both in vitro and in vivo, to elucidate the PK 
profile of bemcentinib and support clinical pharmacology investigations. Bemcentinib has 
good in vitro permeability and is a poor substrate for P-glycoprotein (P-gp), suggesting good 
systemic availability after oral dosing. Animal studies in which bemcentinib was dosed orally 
and intravenously showed high bioavailability indicating that bemcentinib is extensively 
absorbed from the gastrointestinal tract. 
Protein binding of bemcentinib in human plasma was approximately 90% and 91.8% in mice, 
which was similar to that observed in rats, dogs and monkeys. The volume of distribution at 
steady state for bemcentinib was large (30-32 L/kg) and consistent across species, while 
clearance was moderate to high (19 - 43 mL/min/kg) with some variability. The time of the 
maximum observed plasma concentration (tmax) occurred late in the rat (8.9-13.3 hours), dog 
(14.0-18.0 hours), and monkey (6.7-28 hours). Data generated during a mouse absorption, 
distribution, metabolism, and excretion study indicate that bemcentinib is extensively 
distributed into tissue and that tissue concentrations were higher in comparison to plasma 
with a half-life of elimination between 11 and 14 hours. 
Incubation of bemcentinib with human liver cells demonstrate that bemcentinib is a 
low-turnover compound in hepatocytes (half-life [t1/2] >240 mins) and that in liver 
microsomes cytochrome P450 (CYP)3A4 and flavin containing dimethylaniline monoxygenase 
1 are responsible for metabolism. Bemcentinib was found to inhibit CYP3A4 and CYP2D6 
and to induce CYP3A4 and there is a moderate risk of interactions with co-administered 
drugs that are CYP3A4 or CYP2D6 substrates. Bemcentinib was found to weakly inhibit 
OATP1B1 and OCT1 and moderately inhibit P-gp and breast cancer resistance protein. 


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Bemcentinib was found to be an in vitro substrate of breast cancer resistance protein and 
MDR1 ABC (efflux) transporters under monolayer assay conditions. 
1.3. 
Summary of Clinical Experience 
To date, 1 Phase I study (BGBC001) has been completed in healthy volunteers and another 
Phase I food and gastric effect study (BGBC018) has completed recruitment and is in the 
final stages of reporting. Two Phase Ib/II company-sponsored clinical studies (BGBC003 and 
BGBC008) are currently ongoing in patients with advanced cancers. Another Phase Ib/II 
company-sponsored clinical study in non-small cell lung cancer (BGBC004) has completed 
patient recruitment and the clinical study report (CSR) is currently being finalized. One 
Phase II study (BGBC007) evaluating bemcentinib in combination with pembrolizumab in 
patients with triple negative breast cancer was terminated due to pre-defined futility. 
There was also 1 company-sponsored study (BGBC020) and 1 investigator-led study 
(BGBIL019) evaluating bemcentinib plus standard of care in patients hospitalized with 
COVID-19 that have completed patient recruitment. Both studies have had last patient last 
visit and the final CSRs are being developed. In addition, 3 investigator-led studies in the 
oncology setting are ongoing, and 3 have completed patient enrollment. 
Clinical study BGBC001, a Phase 1 first-in-human study that investigated the safety and PK 
of bemcentinib, has completed. Single ascending oral doses of bemcentinib in the range of 50 
to 1500 mg were administered under fasted conditions to 32 healthy male subjects aged 18 to 
45 years. Seven of these subjects were also administered bemcentinib at the same dose under 
fed conditions. 
Bemcentinib was shown to have a predictable PK profile and long plasma half-life, allowing 
for different dosing options. Modelling of the PK data from this study has indicated that the 
most effective approach to rapidly achieving steady state is to administer a series of loading 
doses followed by a lower daily maintenance dose. 
The administration of a single oral dose of bemcentinib was well tolerated up to 1000 mg. A 
single oral dose of 1500 mg was not well tolerated as demonstrated by the review of AEs. 
There were no serious adverse events (SAEs) reported in this study and all AEs resolved 
spontaneously. There were no clinically significant changes from screening in laboratory 
safety parameters, no clinically significant changes in vital signs, and no clinically significant 
abnormalities in electrocardiogram (ECG) parameters during the study. The most commonly 
occurring AEs were gastrointestinal disorders, particularly diarrhea and nausea. 
In clinical study BGBC001, systemic exposure to bemcentinib increased approximately dose 
proportionately. The geometric mean t1/2 was 45.6 to 88.7 hours. Between-subject variability 
in systemic exposure (area under the plasma concentration-time curve [AUC] from time 0 
extrapolated to infinity [AUC0-∞] and maximum observed plasma concentration [Cmax]) to 
bemcentinib at 100 to 1500 mg (PK parameters were only available in 2 subjects at 50 mg) 
was generally high (geometric coefficient of variation of 25.8% to 96.7% for AUC0-∞ and 
Cmax, respectively), most probably reflecting a variable extent of absorption. The median tmax 
was 8 to 23 hours for doses ranging from 50 to 1500 mg, reflecting a slow absorption 
process. The geometric mean value for Cmax after 200 and 400 mg single doses were 36.8 and 


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69.1 ng/mL, respectively. The geometric mean value for AUC0-∞ after 200 and 400 mg single 
doses were 3240 and 6290 h*ng/mL, respectively. 
Following administration of bemcentinib with food to subjects who had previously received 
bemcentinib, there was an increase in systemic exposure in 3 subjects (50% or more), no 
appreciable change in 3 subjects, and an apparent reduction in systemic exposure (40%) in 1 
subject. While Cmax and AUC from time 0 to 48 hours under fed conditions were 29% and 
21% greater, respectively, compared to fasted conditions, the 95% confidence intervals of the 
ratio (fed/fasted) included 100%, indicating lack of statistically significant effect of food on 
bemcentinib with Formulation 1. In a separate healthy volunteer food effect study 
(BGBC018) where 24 subjects received a single dose of 400 mg bemcentinib, the Cmax and 
AUC from time 0 to the time of the last quantifiable concentration (AUC0-tlast) were increased 
by 60% and 70%, respectively, under fed conditions compared to fasted conditions. There 
was also a 60% reduction in the coefficient of variation in the fed state compared to fasted. 
1.4. 
Study Rationale 
The purpose of this study is to determine mass balance recovery and identification of 
potential metabolites of bemcentinib which will enable the planning and design of future 
studies. The previously established 14C labeling site of the active moiety of bemcentinib, 
which was used in the preclinical package for the radioburden calculation, is believed to 
provide the potential to monitor all of the unknown metabolites representing >10% of the 
parent compound as well as to determine the mass balance recovery (urine and feces). 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from collection of blood samples and other study procedures. 
The radioactive dose is an acceptable dose to give to healthy male subjects. More information 
about the known and expected benefits, risks, and reasonably anticipated AEs associated with 
bemcentinib may be found in the IB.1 
2. OBJECTIVES AND ENDPOINTS 
Table 1 shows the objectives and endpoints of the study. 


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Table 1: Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary: 
• 
to determine the mass balance recovery (urine 
and feces) and route and rate of elimination of 
14C-bemcentinib 
• 
to determine the PK of total radioactivity in 
plasma and whole blood and of bemcentinib in 
plasma after a single oral dose of 
14C-bemcentinib in healthy male subjects. 
• 
total radioactivity recovery (fet1-t2) in 
urine and feces 
• 
PK parameters including, but not limited 
to, AUC0-∞, AUC0-tlast, Cmax, tmax, and t1/2 
for bemcentinib in plasma and total 
radioactivity in plasma and whole blood 
and urinary recovery of bemcentinib 
(fet1-t2). 
Secondary: 
• 
to determine the metabolite profile of 
14C-bemcentinib in plasma, urine, and feces 
• 
to identify the chemical structure of the major* 
metabolites of bemcentinib 
*based on the MIST guidelines: >10% of 
bemcentinib parent exposure in plasma after 
oral administration 
• 
to assess safety and tolerability of 
14C-bemcentinib when administered to healthy 
subjects. 
• 
quantitative metabolic profiles of 
bemcentinib in plasma and excreta 
• 
identification of bemcentinib major 
metabolites in plasma (>10% relative 
total drug related exposure) and excreta 
(>10% of excreted dose) 
• 
incidence and severity of AEs 
• 
incidence of laboratory abnormalities, 
based on hematology, clinical chemistry, 
and urinalysis test results 
• 
12-lead ECG parameters 
• 
vital signs measurements 
• 
physical examinations. 
Abbreviations: AE = adverse event; AUC0-∞ = area under the concentration-time curve from time 0 extrapolated to infinity; 
AUC0-tlast = area under the concentration-time curve from time 0 to the time of the last quantifiable concentration; 
Cmax = maximum observed concentration; ECG = electrocardiogram; fet1-t2 = percentage of the dose administered recovered 
over the time interval t1 to t2; MIST = Metabolites in Safety Testing; PK = pharmacokinetics; t1/2 = apparent terminal 
elimination half-life; tmax = time of the maximum observed concentration. 
 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase 1, open-label, nonrandomized, single oral dose study in healthy male 
subjects. 
Potential subjects will be screened to assess their eligibility to enter the study within 28 days 
prior to dose administration. Up to 8 subjects will be enrolled to ensure that 6 subjects 
complete the study. Subjects will be admitted into the study site on Day -1. On the morning 
of Day 1, all subjects will receive a single oral dose of 
 mg containing approximately 
 μCi (
 MBq) of 14C-bemcentinib, 30 minutes after starting a standard high-fat 
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Subjects will be confined to the study site until at least Day 8. Subjects will be discharged 
from the study site on Day 8 if the following discharge criteria are met: 
• ≥90% mass balance recovery, and 
• <1% of the total radioactive dose is recovered in combined excreta (urine and feces) 
in 2 consecutive 24-hour periods. 
If these discharge criteria are not met by Day 8, subjects will be required to remain resident 
until discharge criteria are met, up to Day 15. If criteria are not met by Day 15, subjects may 
be asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential 
basis to allow extrapolation of urinary and fecal excretion. If needed, the 2 additional 24-hour 
nonresidential collections will start on the morning of Days 22 and 29 (to be brought into the 
study site at the end of the collection interval on Days 23 and 30, respectively). If on the 
second occasion the subject has still not met the desired criterion, then the subject will be 
discharged from the study, per investigator and sponsor decision. 
Subjects experiencing emesis during the first 4 hours postdose may be discharged on the 
same day from the study site, provided there are no safety concerns, and after discharge study 
procedures are performed. 
The total duration of study participation for each subject (from screening to outpatient visit [if 
required]) is anticipated to be a maximum of approximately 58 days. 
The start of the study is defined as the date the first subject signs an informed consent form 
(ICF). The point of enrollment occurs at the time of subject number allocation. The end of the 
study is defined as the date of the last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
This study will be open-label because the primary endpoints of the study are considered 
objective. Conducting the study in healthy subjects mitigates the potential confounding 
effects of the disease state and concomitant medications. 
Subjects over 35 years of age will be used to minimize the risk to fertility in healthy subjects. 
Female subjects will be excluded to align with regulatory guidance. The ‘as low as (is) 
reasonably achievable’ (ALARA) principle prescribed by the International Commission on 
Radiological Protection (ICRP)2 recommends that radiation exposure to subjects should be 
kept ALARA; therefore, if no specific reason exists to include females (ie, no available data 
suggest metabolism of the 14C-bemcentinib is different in females versus males), then the 
radiation exposure to female subjects should ideally be kept at zero by not including females 
in this radioactivity study and only enrolling and dosing male subjects. 
Oral administration was chosen since this is the intended clinical route of administration. 
Based on the nonclinical data and the known PK of 14C-bemcentinib, the sample collection 
timing and duration of this study are considered adequate to achieve the study objectives. 


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3.3. 
Selection of Doses in the Study 
A single dose level of 
 mg, approximately 
 μCi (
 MBq) of 14C-bemcentinib, will 
be administered to each subject. This administration is considered adequate to define the 
disposition of 14C-bemcentinib and will deliver a committed effective radiation dose of 
0.997 mSv to each subject. 
The committed effective radiation doses to be received by the subjects as a consequence of 
the administration have been calculated based on the results of a preclinical mass balance 
study and a quantitative whole body autoradiography study.3 The effective radiation dose is 
defined as being within dose limits for members of the public (Category II study, World 
Health Organization)4 with a minor associated risk (risk Category IIb, ICRP).2 
A 
-mg dose of bemcentinib is within the anticipated clinical dose range and is considered 
to be high enough to fully characterize the single oral dose PK of the parent compound. 
Bemcentinib will be dosed after a high-fat breakfast as previous studies have shown a higher 
exposure to bemcentinib in the fed state and less variability in the PK of bemcentinib. 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males of any race, between 35 and 55 years of age, inclusive. 
2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight 
between 50 and 100 kg, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
vital signs measurements, and clinical laboratory evaluations (congenital 
nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s syndrome based on total 
and direct bilirubin] is not acceptable) at screening and check-in and from the 
physical examination at check-in, as assessed by the investigator (or designee). 
4. No clinically significant abnormalities in 12-lead ECG determined within 28 days 
before dose of IMP including average PR > 220 ms and QT interval corrected for 
heart rate using Fridericia’s formula >450 ms. 
5. No history of clinically significant dysrhythmias (long QT features on ECG, sustained 
bradycardia, left bundle branch block, or ventricular arrhythmia), atrial fibrillation, or 
history of familial long QT syndromes. 
6. Will agree to use contraception as detailed in Appendix 4. 
7. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 
8. History of a minimum of 1 bowel movement per day. 


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4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
Medical conditions 
1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 
investigator (or designee). 
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
3. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs (uncomplicated 
appendectomy and hernia repair will be allowed). 
4. Positive hepatitis panel and/or positive human immunodeficiency virus test 
(Appendix 2). 
Prior/concomitant therapy 
5. Administration of a COVID-19 vaccine in the past 30 days prior to dosing. 
Note: further details regarding COVID‑19 testing (including procedures for subjects 
who test positive at any time throughout clinical research unit confinement) are 
specified in a separate document. 
6. Use or intend to use any medications/products known to alter drug absorption, 
metabolism, or elimination processes, including St. John’s wort, within 30 days prior 
to check-in, unless deemed acceptable by the investigator (or designee). 
7. Use or intend to use any prescription medications/products within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
8. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
9. Use or intend to use any nonprescription medications/products including vitamins, 
minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior 
to check-in, unless deemed acceptable by the investigator (or designee). 
Prior/concurrent clinical study experience 
10. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 90 days prior to dosing. 
11. Subjects who have participated in any clinical study involving a radiolabeled 
investigational product within 12 months prior to check-in. 
12. Have previously completed or withdrawn from this study or any other study 
investigating bemcentinib, and have previously received bemcentinib. 


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Diet and lifestyle 
13. Alcohol consumption of > 28 units per week for males. One unit of alcohol equals 
½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of 
spirits. 
14. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
at screening or check-in. 
15. History of alcoholism or drug/chemical abuse within 2 years prior to check-in. 
16. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in. 
17. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
Other exclusions 
18. Receipt of blood products within 2 months prior to check-in. 
19. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
20. Poor peripheral venous access. 
21. Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial 
X-ray, computed tomography scan, barium meal) or current employment in a job 
requiring radiation exposure monitoring within 12 months prior to check-in. 
22. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 
Subjects may previously have been screened on a generic basis to determine their eligibility 
for inclusion in Phase 1 clinical studies conducted at the study site. If generic screening was 
performed within the specified study screening window, selected study-specific procedures 
will be repeated either at an additional screening visit or on admission to the study site on 
Day -1. 
4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Subjects will be assigned 
a subject number prior to dosing. Assignment of subject numbers will be in ascending order 
and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
A replacement subject (see Section 4.4) will be assigned a subject number corresponding to 
the number of the subject he is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 


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4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw from the study at any time. In addition, a subject will be 
withdrawn if any of the following criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form. If a 
subject is withdrawn from the study, efforts will be made to perform all discharge 
assessments, if possible (Appendix 6). Other applicable safety-related procedures may be 
performed at the investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is 
in-house, these procedures should be performed before the subject is discharged from the 
clinic. The investigator (or designee) may also request that the subject return for an additional 
follow-up visit. All withdrawn subjects will be followed until resolution of all their AEs or 
until the unresolved AEs are judged by the investigator (or designee) to have stabilized. 
The replacement of subjects withdrawn from the study will be discussed between the 
investigator and sponsor. 
4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• AEs unknown to date (ie, not previously reported in any similar investigational study 
drug trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development. 
5. STUDY TREATMENTS 
5.1. 
Description, Storage, Packaging, and Labeling 
Active pharmaceutical ingredient (API), as an off-white to colored solid (with a target clinical 
specific activity of 
 µCi/mg) will be supplied by the sponsor and radiolabeled API 


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(powder) will be supplied by the sponsor from ALMAC (UK), along with the batch number, 
Good Manufacturing Practice certificate, and certificates of analysis. 
The study site will manufacture and label the IMP from bulk API and excipient supplies, such 
that each unit dose contains a total of 
 mg bemcentinib as two 
-mg capsules 
containing approximately 
 μCi (
 MBq) of 14C-bemcentinib. A certificate of release 
authorized by a Qualified Person from a listed country or United Kingdom will also be issued 
for the IMP prior to administration to subjects. 
The sponsor will supply a sufficient quantity of the applicable API (target of  mCi) for the 
manufacture of the unit doses at the study site. All excipients and capsules will be sourced by 
the study site. Specific instructions regarding dose preparation and storage of materials will 
be mutually agreed upon between the sponsor and the appropriate clinical staff and will be 
presented in a separate document. 
The API and IMP will be stored according to the instructions on the label at the study site in a 
location that is locked with restricted access. The IMP label will be the responsibility of 
Labcorp, and the API label will be the responsibility of the sponsor. 
5.2. 
Study Treatment Administration 
Each dose of 14C-bemcentinib will be administered orally with 240 mL of room temperature 
water. All subjects will fast overnight (at least 8 hours) and will consume a standard high-fat 
breakfast 30 minutes prior to dosing. Subjects will refrain from consuming water for 1 hour 
prior to dosing. Subjects will refrain from consuming water until 2 hours postdose, excluding 
the amount of water consumed at dosing, and will fast until 4.5 hours postdose. At all other 
times during the study, subjects may consume water ad libitum. 
Subjects will be dosed in numerical order while standing and will not be permitted to lie 
supine for 2 hours after administration of 14C-bemcentinib except as necessitated by the 
occurrence of an AE(s) and/or study procedures. 
Except when they are using the toilet, study subjects will be observed for approximately 
4 hours postdose to ensure that they are not experiencing AEs, becoming nauseated, or 
experiencing emesis. 
5.3. 
Randomization 
This is a nonrandomized study. The study has a single treatment group. 
5.4. 
Blinding 
This is an open-label study. 


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5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after oral administration, visual inspection of the mouth will be 
performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed. 
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of the study 
supplies received. In addition, an accurate drug disposition record will be kept, specifying the 
amount dispensed to each subject and the date of dispensing. This drug accountability record 
will be available for inspection at any time. At the completion of the study, the original drug 
accountability record will be available for review by the sponsor upon request. 
For unit doses, the empty used unit dose containers will be discarded upon satisfactory 
completion of the compliance and accountability procedures. Any unused assembled unit 
doses will be retained until completion of the study. 
At the completion of the study, all unused supplies will be returned to the sponsor or disposed 
of by the study site, per the sponsor’s written instructions. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from use of any prescription or nonprescription medications/products 
during the study until discharge, unless the investigator (or designee) and/or sponsor have 
given their prior consent. 
A mild laxative (ie, Milk of Magnesia®, Colace®) may be used to help with bowel 
movements if necessary. Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) 
is an acceptable concomitant medication. The administration of any other concomitant 
medications during the study is prohibited without prior approval of the investigator (or 
designee), unless its use is deemed necessary for treatment of an AE. Any medication taken 
by a subject during the course of the study and the reason for its use will be documented in 
the source data. 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized, high-fiber diet at 
scheduled times that do not conflict with other study-related activities. Prune juice may be 
administered on an as-needed basis to aid in normal bowel function and will not be 
considered a concomitant medication. Subjects will be fasted overnight (at least 8 hours) 
before collection of blood samples for safety laboratory tests. 


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Subjects will consume a high-fat breakfast (contents are detailed in Table 2) before dosing. 
Subjects should start the meal 30 minutes prior to administration of the IMP. Study subjects 
should eat this meal in 30 minutes or less. The drug product should be administered 
30 minutes after start of the meal. 
Table 2: High-fat Breakfast Content 
 
High-fat Breakfast 
 
120 g fried eggs (2 eggs) in vegetable oil 
50 g bacon (2 rashers) 
72 g toasted white bread (2 slices) 
13 g butter (2 pats) 
108 g hash brown (3 each) 
240 g whole milk 
 
 Total calories: 973 kcal 
 
This high-fat meal contains the equivalent of approximately 150 protein calories, 
250 carbohydrate calories, and 500 to 600 fat calories. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until discharge. 
Caffeine-containing foods and beverages will not be allowed from 36 hours before check-in 
until discharge. 
Consumption of alcohol will not be permitted from 36 hours prior to check-in until discharge. 
6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until discharge. 
6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until 
discharge and will otherwise maintain their normal level of physical activity during this time 
(ie, will not begin a new exercise program nor participate in any unusually strenuous physical 
exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after discharge. 


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7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• blood samples for PK assessments 
• urine and fecal collections for PK assessments 
• any other procedures. 
7.1. 
Pharmacokinetic Assessments 
Table 3 shows the PK assessments to be carried out. 
Table 3: Pharmacokinetic Assessments 
Sample 
Radioanalysis 
Pharmacokinetics 
(bemcentinib) 
Metabolite 
profiling 
 
Whole blood 
X 
Plasma 
X 
X 
X 
Urine 
X 
X 
X 
Feces 
X 
X 
 
7.1.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples will be collected by venipuncture or cannulation at the times indicated in the 
Schedule of Assessments in Appendix 6 for determination of bemcentinib concentration, total 
radioactivity, and metabolite profiling and identification. 
Approximately 1 × 2 mL blood sample will be collected for total radioactivity in whole blood 
and approximately 1 × 6 mL blood sample will be collected for total radioactivity in plasma. 
Approximately 1 × 4 mL blood sample will be collected for bemcentinib concentration in 
plasma. Approximately 1 × 10 mL blood sample will be collected for metabolite profiling 
and identification in plasma. 
7.1.2. 
Pharmacokinetic, Total Radioactivity, and Metabolite Urine and Feces 
Collection and Processing 
Urine will be collected over the time intervals indicated in the Schedule of Assessments in 
Appendix 6 for determination of bemcentinib concentration, total radioactivity, and 
metabolite profiling and identification. Procedures for collection, processing, and shipping of 
urine collections will be detailed in a separate document. 


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Feces will be collected over the time intervals indicated in the Schedule of Assessments in 
Appendix 6 for determination of total radioactivity, and, where possible, metabolite profiling 
and identification. If possible, a single baseline fecal sample will be collected from after 
check-in on Day -1 until just prior to dose administration on Day 1. Procedures for collection, 
processing, and shipping of fecal collections will be detailed in a separate document. 
7.1.3. 
Vomitus Sample Collection 
For subjects experiencing emesis within 4 hours following oral dosing, vomitus will be 
collected. Attempts will be made to collect vomitus from subjects experiencing emesis after 
4 hours postdose. All vomitus collected will be stored for possible analysis as deemed 
appropriate. 
7.1.4. 
Analytical Methodology 
Plasma and urine concentrations of bemcentinib will be determined using a validated 
analytical procedure. Urine, and feces total radioactivity will be determined with liquid 
scintillation counting. Whole blood and plasma total radioactivity will be determined by 
accelerated mass spectrometry. Profiling and identification of metabolites in plasma, urine, 
and, where possible, feces will be conducted using standard laboratory procedures. Specifics 
of the analytical methods will be provided in separate documents. 
7.2. 
Safety and Tolerability Assessments 
7.2.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF to final 
discharge from the study. Subjects will be observed for any signs or symptoms and asked 
about their condition by open questioning, such as ‘How have you been feeling since you 
were last asked?’, at least once each day while resident at the study site and at each study 
visit. Subjects will also be encouraged to spontaneously report AEs occurring at any other 
time during the study. 
Any AEs and remedial action required will be recorded in the subject’s source data. The 
nature, time of onset, duration, and severity will be documented, together with an 
investigator’s (or designee’s) opinion of the relationship to study treatment. 
Adverse events recorded during the course of the study will be followed up, where possible, 
until resolution or until the unresolved AEs are judged by the investigator (or designee) to 
have stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.2.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 


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Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. 
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.2.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, and oral body temperature will be assessed at the 
times indicated in the Schedule of Assessments in Appendix 6. Vital signs may also be 
performed at other times if judged to be clinically appropriate or if the ongoing review of the 
data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly, and repeated once if outside the relevant clinical 
reference range. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.2.4. 
12-Lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. 
Single 12-lead ECGs will be repeated once if the investigator deems a repeat is indicated. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 
12-lead ECG. 
7.2.5. 
Physical Examination 
A full physical examination or symptom-directed physical examination will be performed at 
the timepoints specified in the Schedule of Assessments in Appendix 6. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
No formal statistical assessment of sample size has been conducted. The sample size chosen 
for this study is common in human radiolabeled studies and is considered sufficient to 
achieve the objectives of the study. Up to 8 subjects will be enrolled and studied as a single 
group in order that 6 complete the study. 


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8.2. 
Analysis Populations 
8.2.1. 
Safety Population 
The safety population will include all subjects who received a dose of radiolabeled study 
treatment (14C-bemcentinib). 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received a dose of radiolabeled study 
treatment (14C-bemcentinib) and have at least 1 valid PK concentration. 
8.2.3. 
All Subjects Population 
The all subjects population will include all subjects who signed the ICF and had any study 
assessment recorded in the database per the protocol. 
8.3. 
Pharmacokinetic Analyses 
Pharmacokinetic parameters of bemcentinib in plasma and urine, and total radioactivity in 
plasma and whole blood will be determined using standard noncompartmental methods, 
where data allow. Full details of PK parameters will be presented in the statistical analysis 
plan for this study. 
Pharmacokinetic parameters will be listed and summarized. No formal statistical analysis will 
be performed. 
The mass balance recovery of total radioactivity (percentage of the dose administered 
recovered in urine, feces, and total excreta) will be calculated by the radioanalysis laboratory. 
8.4. 
Safety Analysis 
Safety parameters will be listed and summarized. No formal statistical analysis of safety data 
is planned. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
8.5. 
Interim Analysis 
No formal interim analyses are planned for this study. 
9. REFERENCES 
1. BerGenBio. Bemcentinib, formerly known as BGB324 – Investigator’s Brochure 
(Version 16). 27 April 2022. 
2. ICRP, 1992. Radiological Protection in Biomedical Research. ICRP Publication 62, Ann. 
ICRP, 22(3). 
3. Study 8442959: Absorption, Distribution, Metabolism, and Excretion of Bemcentinib 
(BGB324) After a Single Oral Administration of 14C-Bemcentinib (BGB324) to Mice, 
Madison, Wisconsin, United States of America. 


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4. World Health Organization, 1977. Use of ionising radiation and radionuclides on human 
beings for medical research, training and nonmedical purposes. Technical report series 
No. 611, Geneva. 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product, which does not necessarily have 
a causal relationship with this treatment. An AE can therefore be any unfavorable and/or 
unintended sign (including a clinically significant abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a study treatment, whether or not related to the 
study treatment. 
Assessment of Severity 
The investigator (or designee) will be asked to provide an assessment of the severity of the 
AE using the following categories: 
• Mild: Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily 
living. 
• Moderate: Usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 
• Severe: Interrupts usual activities of daily living, significantly affects clinical status, 
or may require intensive therapeutic intervention. 
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
• Not Related: The AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions. 
• Unlikely Related: The temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE. 
• Possibly Related: The AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical state or the 
study procedures/conditions. 
• Related: The AE follows a reasonable temporal sequence from administration of the 
drug, abates upon discontinuation of the drug, follows a known or hypothesized 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced. 
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the investigational medicinal 
product (IMP) or study procedures at discharge will be followed up, where possible, until 


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resolution or until the unresolved AE is judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. Any subject 
who has an ongoing AE that is not related or unlikely related to the IMP or study procedures 
at the discharge visit can be closed out as ongoing at the investigator’s discretion. 
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug which is noxious and unintended and 
that occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or for modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, investigator’s 
brochure for an unapproved IMP). 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose either: 
• results in death 
• is life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
• results in a congenital anomaly/birth defect 
• results in an important medical event (see below). 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor. 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 


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hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the electronic case report form. If anything untoward is reported during the 
procedure, this must be reported as an AE and either ‘serious’ or ‘nonserious’ attributed 
according to the usual criteria. 
Serious Adverse Event Reporting 
Serious AEs that occur between the time of signing the informed consent form and until 
28 days after the dose of study treatment, regardless of relationship to the study treatment, 
must be reported within 24 hours of knowledge of the event to the sponsor or designee. In 
addition, if the investigator learns at any time of an SAE which is believed to be related to the 
study treatment then this must be reported to the sponsor, even if more than 28 days have 
elapsed since the dose of study treatment. 
Serious AE reporting will be conducted as described in the safety management plan. The 
SAE form will collect all relevant data concerning the AE, including: details of the nature of 
the symptoms, time of onset, duration, and severity, together with an investigator’s (or 
designee’s) opinion of the relationship to study treatment, and any action taken in relation to 
the planned administration of study treatment. In addition, the investigator should provide 
relevant medical history, concomitant medications, laboratory or diagnostic test reports, 
details of any treatment for the SAE, and all other pertinent medical information. 
Pregnancy 
Pregnancy (paternal exposure to study treatment) does not meet the definition of an AE. 
However, to fulfill regulatory requirements any pregnancy should be reported following the 
SAE process to collect data on the outcome for both mother and fetus. 


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Appendix 2: Clinical Laboratory Evaluations 
 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubin 
Gamma-glutamyl transferase 
Glucose 
Inorganic phosphate 
Potassium 
Sodium 
Total bilirubina 
Total CO2 
Total protein 
Troponin I 
Uric acid 
Hematocrit 
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count 
WBC differential: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
Blood 
Glucose 
Ketones 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination 
Serologyb: 
Drug screen: 
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency virus 
(HIV-1 and HIV-2) antibodies and 
p24 antigen 
Including but not limited to: 
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol/ 
cannabinoids 
Tricyclic antidepressants 
Cotinine testc 
Alcoholc 
a Direct and total bilirubin will always be measured 
b Only analyzed at screening 
c Screening and Day -1 check-in 


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Appendix 3: Total Blood Volume 
The following blood volumes are the maximum that will be withdrawn for each subject. 
 
Up to Day 15 
 
Volume per blood 
sample (mL) 
Maximum number 
of blood samples 
Total amount of 
blood (mL) 
Clinical Laboratory 
evaluations 
7.5 
3 
22.5 
Serology 
3.5 
1 
3.5 
Whole blood for 
pharmacogenetic profiling 
2 
1 
2 
Whole blood for total 
radioactivity 
2 
28 
56 
Plasma for total radioactivity 
6 
28 
168 
Plasma for bemcentinib 
4 
28 
112 
Plasma for metabolite 
profiling 
10 
22 
220 
Total: 
584 
 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 600 mL. 


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Appendix 4: Contraception Guidance 
Contraception Guidance 
Male Subjects 
Male subjects with partners of childbearing potential must use a highly effective method of 
contraception (ie vasectomy) or 2 effective methods of contraception from check-in until 
90 days after receiving the IMP dose. Acceptable methods of contraception for female 
partners include: 
Highly effective: 
• Combined (oestrogen and progestogen containing) hormonal contraception (oral, 
intravaginal and transdermal) associated with inhibition of ovulation 
• Progestogen-only hormonal contraception (oral, injectable and implantable) 
associated with inhibition of ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal 
occlusion]) 
• Vasectomy (surgery that has been performed 90 days prior to the screening visit, with 
verbal confirmation of surgical success) – male subjects. 
Effective: 
• Progestogen-only oral hormonal contraception (where inhibition of ovulation is not 
the primary mode of action) 
• Male or female condom with spermicide. 
To prevent exposure of any partner (male or female) during non-vaginal intercourse to the 
semen from a male subject who has been exposed to the IMP, the following contraception 
must be used: 
• Condom. 
The chosen contraception method(s) must be followed from the IMP dose until at least 
90 days after receiving the IMP dose. Male subjects (even with a history of vasectomy) must 
not have unprotected sexual intercourse with a female who is pregnant or breastfeeding 
during the study and for 90 days after receiving the IMP dose. Male subjects must not donate 
sperm from receiving the IMP dose and for at least 90 days after receiving the IMP dose. 


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Sexual Abstinence and Same-sex Relationships 
A subject who practices total abstinence is required to identify contraceptive methods he will 
use in the event of sexual activity. Periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods) and withdrawal are not acceptable methods of 
contraception. 
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the informed 
consent form becomes engaged in a heterosexual relationship, they must agree to use 
contraception as described previously. 


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Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines. 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines. 
• Applicable laws and regulations. 
The protocol, protocol amendments, informed consent form (ICF), investigator’s brochure, 
and other relevant documents must be submitted to an ethics committee (EC) by the 
investigator and reviewed and approved by the EC before the study is initiated. 
Any substantial protocol amendments, likely to affect the safety of the subjects or the conduct 
of the study, will require EC and regulatory authority (as locally required) approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study subjects or any nonsubstantial changes, as defined by 
regulatory requirements. 
The study will additionally be approved by the Administration of Radioactive Substances 
Advisory Committee. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 
Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatment, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following discussion of the study with study site personnel, subjects will sign the ICF in the 
presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 


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Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in the 
electronic case report forms (eCRFs), study-related forms, study reports, or any related 
publications. Subject and investigator personal data will be treated in compliance with all 
applicable laws and regulations. In the event the study protocol, study report, or study data 
are included in a public registry, all identifiable information from individual subjects or 
investigator will be redacted according to applicable laws and regulations. 
The subject must be informed that his personal study-related data will be used by the sponsor 
in accordance with local data protection law. The level of disclosure must also be explained 
to the subject. The subject must also be informed that his study-related data may be examined 
by sponsor or contract research organization (CRO) auditors or other authorized personnel 
appointed by the sponsor, by appropriate EC members, and by inspectors from regulatory 
authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
• All relevant subject data relating to the study will be recorded on eCRFs unless 
directly transmitted to the sponsor or designee electronically (eg, laboratory data). 
The investigator is responsible for verifying that data entries are accurate and correct 
by electronically signing the eCRF. 
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
• The investigator must permit study-related monitoring, audits, EC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Labcorp Drug Development is responsible for the data management of this study 
including quality checking of the data. Predefined agreed risks, monitoring thresholds, 
quality tolerance thresholds, controls, and mitigation plans will be documented in a 
project management plan. Additional details of quality checking to be performed on 
the data may be included in a data management plan. 
• A study monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 


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• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive for at least 5 years after 
the end of the study unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor. 
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture system on an eCRF in a timely fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to Labcorp Drug Development electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan. 
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the electronic data capture system’s 
electronic signature procedure. These signatures will indicate that the investigator reviewed 
and approved the data on the eCRF, data queries, and site notifications. 
Publications 
The sponsor holds all publication rights to the data obtained from this study. Before any data 
from this study are published on the initiative of the investigator, a manuscript will be sent to 
the sponsor for review and approval at least 30 days prior to submission to the publisher. 


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Appendix 6: Schedule of Assessments 


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Study Procedures 
Screenin 
g 
Day - 
1 
Days 1 to 8a 
Dischargeb 
Days 8 to 15 
Outpatient 
Visit 
Days 22 to 
29 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
X 
Demographic data 
X 
Medical history 
X 
Xc 
Urinary drug screen 
X 
X 
Alcohol breath test 
X 
X 
Cotinine test 
X 
X 
Serology 
X 
Height and body weight 
X 
Blood sampling for 
pharmacogenetic profilingd 
Day 1 (predose) 
Study residency: 
Check-in 
X 
Check-out 
X 
Nonresidential visit 
X 
X 
Study treatment 
administration: 
14C-bemcentinib 
Day 1 oral administration (0 hours) 
(30 minutes after starting a high-fat 
breakfast) 
Pharmacokinetics: 
Blood sampling for 
bemcentinib concentration 
(plasma) 
Predose, 15 and 30 minutes, 1, 1.5, 2, 
2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 
96, 120, 144, and 168 hours following 
the oral dose 
192, 216, 240, 264, 288, 312, 
and 336 hours postdose 
Blood sampling for total 
radioactivity (whole blood and 
plasma) 
Predose, 15 and 30 minutes, 1, 1.5, 2, 
2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 
96, 120, 144, and 168 hours following 
the oral dose 
192, 216, 240, 264, 288, 312, 
and 336 hours postdosea 


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Study Procedures 
Screenin 
g 
Day - 
1 
Days 1 to 8a 
Dischargeb 
Days 8 to 15 
Outpatient 
Visit 
Days 22 to 
29 
Blood sampling for metabolite 
profiling and identification 
(plasmag) 
Predose, 15 and 30 minutes, 1, 1.5, 2, 
2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 
72, 96, 120, 144, and 168 hours 
following the oral dose 
Urine collection for 
bemcentinibj concentration, 
total radioactivity, and 
metabolite profilingg and 
identification 
Predose (-3 to 0 hours)h, 0 to 12, 12 to 
24, 24 to 48, 48 to 72, 72 to 96, 96 to 
120, 120 to 144, 144 to 168 hours 
postdosei 
168 to 192, 192 to 216, 216 to 
240, 240 to 264, 264 to 288, 288 
to 312, and 312 to 336 hours 
postdosea 
Days 22 to 
Day 23, 
Days 29 to 
Day 30e 
Fecal collection for total 
radioactivity and metabolite 
profilingg and identification 
Predose (from check-in to 0 hours)h, 0 
to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 
96, 96 to 120, 120 to 144, 144 to 168 
hours postdosei 
168 to 192, 192 to 216, 216 to 
240, 240 to 264, 264 to 288, 288 
to 312, and 312 to 336 hours 
postdosea 
Days 22 to 
Day 23, 
Days 29 to 
Day 30e 
Safety and tolerability: 
Adverse event recording 
X 
X 
Ongoing 
X 
X 
Prior/concomitant medication 
monitoring 
X 
X 
Ongoing 
X 
X 
Clinical chemistry, hematology, 
and urinalysis 
X 
X 
X 
Blood pressure and pulse ratef 
X 
X 
Predose and 2, 4, 8, 24, and 48 hours 
postdose 
X 
Oral body temperature 
X 
X 
X 
12-lead electrocardiogram 
X 
X 
Predose and 2 and 24 hours postdose 
X 
Physical examination 
X 
Xk 
a 
Additional 24-hour collections (urine and feces) for radioanalysis may continue up to Day 15 if mass balance recovery is not adequate or radioactivity is still being 
eliminated in excreta. Subjects will be discharged when the following criteria are met: ≥90% mass balance recovery and <1% of the total radioactive dose is recovered in excreta (urine 
and feces) in 2 consecutive 24-hour periods. If this is the case, subjects will be asked to remain resident within the clinical research unit for a further period (up until Day 15). 
b 
Discharge will be from Day 8 to Day 15 depending on radioactivity elimination. 
c 
Interim medical history. 


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d 
On Day 1, a blood sample will be collected and stored for subsequent assessment of the pharmacogenetic profile of bemcentinib in order to explore the influence of 
pharmacogenetic factors on the pharmacokinetics and safety. 
e 
If discharge criteria (mass balance recovery) is not adequate (≤90% mass balance recovery, and >1% of the total radioactive dose is recovered in excreta [urine and feces] in 
2 consecutive 24-hour periods) are not met by Day 8, subjects will be required to remain resident until discharge criteria are met, up to Day 15. If criteria are not met by Day 15, 
subjects may be asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential basis to allow extrapolation of urinary and fecal excretion. If needed, the 2 
additional 24-hour nonresidential collections will start on the morning of Days 22 and 29 (to be brought into the study site at the end of the collection interval on Days 23 and 30, 
respectively). If on the second occasion the subject has still not met the desired criterion, then the subject will be discharged from the study, per investigator and sponsor decision. 
f 
Blood pressure and pulse rate will be measured singly followed by at least 5 minutes in the supine position. 
g 
Plasma samples for metabolite profiling will be selected after confirming the total radioactivity time profile. Urine and fecal samples for metabolite profiling will be selected 
after confirming total radioactivity time profile in excreta. 
h 
For the predose timepoint for urine and fecal collection, a single sample will be collected within 3 hours and 24 hours prior to dosing, respectively. 
i 
Collection may cease after 168 hours (Day 8) if <1% of the total radioactive dose is recovered in excreta (urine and feces) in 2 consecutive 24-hour collection periods and if 
mass balance recovery is ≥90% (if 2 of the 3 recovery criteria are fulfilled, the investigator and sponsor will decide whether they require the subject to return to the unit). 
j 
Analysis of pharmacokinetics will be performed on urine samples collected up to and including 168 hours postdose, only. 
k 
Symptom-directed physical examination.