A Clinical Study of Bemcentinib With Standard of Care Chemoimmunotherapy in Untreated Advanced/Metastatic Non-small Cell Lung Cancer Patients With a Mutation in the STK11 Gene

Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation

The primary purpose of this study is to determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (1L) treatment in participants with locally advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations and to determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in participants with locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with serine/threonine kinase 11 (STK11) mutation and no actionable mutations.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Bemcentinib

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44277
    • Hôpital prive du Confluent SAS, Departement d'oncologie
  • Nice, France, 6189
    • Centre Antoine Lacassagne
  • Paris, France, 75015
    • Hôpital Europeen Georges Pompidou (HEGP), Service de cancérologie
  • Villejuif, France, 94805
    • Institut Gustave Roussy, Service de médecine
• Greece
  • Athens, Greece, 115 26
    • Henry Dunant Hospital Center, 4th Oncology Department
  • Athens, Greece, 115 27
    • Sotiria General Hospital of Chest Diseases, 3rd Department of Internal Medicine, Oncology Unit
  • Athens, Greece, 11528
    • General Hospital of Athens Alexandra, Department of the Clinical Therapeutics, Medical Oncology Unit
  • Larissa, Greece, 41110
    • University General Hospital of Larissa, Oncology Clinic
• Hungary
  • Budapest, Hungary, 1121
    • Országos Korányi Pulmonológiai Intézet
  • Budapest, Hungary, 1083
    • Semmelweis University- Department of Pulmonology
  • Székesfehérvár, Hungary, 8000
    • Fejer County St. Gyorgy Hospital
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi
  • Lucca, Italy, 55100
    • Ospedale San Luca
  • Milan, Italy, 20141
    • IRCCS - Istituto Europeo di Oncologia IEO
  • Rome, Italy, 144
    • IFO Regina Elena
• Poland
  • Bialystok, Poland, 15-540
    • Uniwersytecki Szpital Kliniczny w Bialymstoku, II Klinika Chorob Pluc, raka płuca i chorób wewnętrznych
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki (Iczmp)
  • Lublin, Poland, 20090
    • Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie
  • Poznan, Poland, 60693
    • MedPolonia Sp z oo
• Spain
  • Badalona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center, Oncology service
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología (FIVO)
• United States
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
  • New York
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center - Duke Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Histologically-confirmed or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 1b) targetable with first-line treatment.
• Histologically-confirmed or cytologically confirmed diagnosis of stage of advanced (Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC, Edition 8) non-squamous NSCLC with STK11 mutation, not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (phase 2a) targetable with first-line treatment.
• Have not received prior systemic treatment for their advanced/metastatic NSCLC
• Have measurable disease per RECIST 1.1 as assessed by the investigator

Main Exclusion Criteria:

• Has received any prior chemotherapy or biological therapy for locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) adenocarcinoma of the lung
• Received radiation therapy within 2 weeks prior to starting study treatment or has not recovered (i.e. <=Grade 1 at baseline) from AEs due to a previous radiation therapy
• Major surgery within 28 days prior to start of study treatment and failure to have recovered adequately from the complications of the surgery/intervention prior to the first dose of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b Cohort 1: Bemcentinib 75 mg; Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 75 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).	Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous (IV) infusion as part of CIT every 3 weeks.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks up to 4 cycles. Each cycle = 21 days.; Drug: Bemcentinib; Bemcentinib capsules will be administered daily orally.
Experimental: Phase 1b Cohort 2: Bemcentinib 100 mg; Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 100 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).	Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous (IV) infusion as part of CIT every 3 weeks.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks up to 4 cycles. Each cycle = 21 days.; Drug: Bemcentinib; Bemcentinib capsules will be administered daily orally.
Experimental: Phase 1b Cohort 3: Bemcentinib 150 mg; Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 150 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).	Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous (IV) infusion as part of CIT every 3 weeks.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks up to 4 cycles. Each cycle = 21 days.; Drug: Bemcentinib; Bemcentinib capsules will be administered daily orally.
Experimental: Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b); Participants with previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as identified by Next Generation Sequencing (NGS) and without actionable mutations will receive bemcentinib second dose, at RP2D identified in Phase 1b, once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).	Drug: Pemetrexed; Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab will be administered as an intravenous (IV) infusion as part of CIT every 3 weeks.; Drug: Carboplatin; Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks up to 4 cycles. Each cycle = 21 days.; Drug: Bemcentinib; Bemcentinib capsules will be administered daily orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2a: Objective Response Rate (ORR) at 6 Months	ORR is defined as percentage of participants with complete response and partial response per RECIST 1.1.	6 months
Phase 2a: Objective Response Rate (ORR) at 12 Months	ORR is defined as percentage of participants with complete response and partial response per RECIST 1.1.	12 months
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)	DLT graded using NCI CTCAE Version 5.0 based on the Investigator assessment.	Cycle 1 (the first 21 days of treatment)

Collaborators and Investigators

• Sponsor: BerGenBio ASA

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Actual): April 3, 2025
• Study Completion (Actual): April 3, 2025

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 19, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Carboplatin; pembrolizumab; bemcentinib
• Other Study ID Numbers: BGBC016; 2024 511007 41 00 (Ctis); U1111-1312-8770 (Other Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data that underlie the results reported in the article, after deidentification [text, tables, figures and appendices].

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No