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 1

Terminated

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: Bemcentinib; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin

• Registration Number: NCT05469178
• Lead Sponsor: BerGenBio ASA

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-19
• Study First Submitted QC: 2022-07-19
• Study First Posted: 2022-07-21
• Study Start: 2023-03-06
• Primary Completion: 2025-01-31
• Study Completion: 2025-04-03
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b Cohort 1: Bemcentinib Dose 1	Pemetrexed	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 1 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).
Phase 1b Cohort 1: Bemcentinib Dose 1	Bemcentinib	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 1 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).
Phase 1b Cohort 1: Bemcentinib Dose 1	Pembrolizumab	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 1 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).
Phase 1b Cohort 1: Bemcentinib Dose 1	Carboplatin	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 1 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).
Phase 1b Cohort 2: Bemcentinib Dose 2	Bemcentinib	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 2 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).
Phase 1b Cohort 2: Bemcentinib Dose 2	Pembrolizumab	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 2 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).
Phase 1b Cohort 2: Bemcentinib Dose 2	Pemetrexed	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 2 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).
Phase 1b Cohort 2: Bemcentinib Dose 2	Carboplatin	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 2 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).
Phase 1b Cohort 3: Bemcentinib Dose 3	Bemcentinib	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 3 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).
Phase 1b Cohort 3: Bemcentinib Dose 3	Pembrolizumab	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 3 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).
Phase 1b Cohort 3: Bemcentinib Dose 3	Pemetrexed	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 3 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).
Phase 1b Cohort 3: Bemcentinib Dose 3	Carboplatin	Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib dose 3 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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first as determined from Phase 1b)	Bemcentinib	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, 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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first as determined from Phase 1b)	Pembrolizumab	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, 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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first as determined from Phase 1b)	Pemetrexed	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, 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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first as determined from Phase 1b)	Carboplatin	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, 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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second as determined from Phase 1b)	Bemcentinib	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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second as determined from Phase 1b)	Pembrolizumab	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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second as determined from Phase 1b)	Pemetrexed	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).
Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second as determined from Phase 1b)	Carboplatin	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).

Primary Outcome Measures

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

Trial Locations

Locations (34)

Fejer County St. Gyorgy Hospital; 🇭🇺 Szekesfehervar, Hungary

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

MD Anderson Cancer Center, Oncology service; 🇪🇸 Madrid, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hôpital prive du Confluent SAS, Departement d'oncologie; 🇫🇷 Nantes Cedex 2, France

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami Beach, Florida, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Duke University Medical Center - Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

Tennessee Oncology PLLC; 🇺🇸 Nashville, Tennessee, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Hôpital Europeen Georges Pompidou (HEGP), Service de cancérologie; 🇫🇷 Paris, France

Institut Gustave Roussy, Service de médecine; 🇫🇷 Villejuif, France

Henry Dunant Hospital Center, 4th Oncology Department; 🇬🇷 Athens, Greece

Sotiria General Hospital of Chest Diseases, 3rd Department of Internal Medicine, Oncology Unit; 🇬🇷 Athens, Greece

General Hospital of Athens Alexandra, Department of the Clinical Therapeutics, Medical Oncology Unit; 🇬🇷 Athens, Greece

University General Hospital of Larissa, Oncology Clinic; 🇬🇷 Larissa, Greece

Semmelweis University- Department of Pulmonology; 🇭🇺 Budapest, Hungary

Orszagos Koranyi Pulmonologiai Intezet; 🇭🇺 Budapest, Hungary

Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi; 🇮🇹 Bologna, Italy

Ospedale San Luca; 🇮🇹 Lucca, Italy

IRCCS - Istituto Europeo di Oncologia IEO; 🇮🇹 Milan, Italy

IFO Regina Elena; 🇮🇹 Rome, Italy

Uniwersytecki Szpital Kliniczny w Bialymstoku, II Klinika Chorob Pluc, raka płuca i chorób wewnętrznych; 🇵🇱 Bialystok, Poland

Instytut Centrum Zdrowia Matki Polki (ICZMP); 🇵🇱 Lodz, Poland

Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie; 🇵🇱 Lublin, Poland

MedPolonia Sp z oo; 🇵🇱 Poznan, Poland

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Fundacion Instituto Valenciano de Oncologia (FIVO); 🇪🇸 Valencia, Spain