A Study to Investigate the Safety, Tolerability, and Preliminary Anti-tumor Activity of Bemcentinib in Combination With Pembrolizumab Plus Pemetrexed and Carboplatin in Adult Participants With Untreated Non-squamous Non-small Cell Lung Cancer

BerGenBio

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Carboplatin; Drug: Bemcentinib; Drug: Pembrolizumab; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT05469178

BGBC016

2019-003806-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 64 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)
• 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)
• 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
• Has an EGFR Exon 19 Deletion or L858R mutation, EGFR S768I, L861Q, and/or G719X mutations, ALK gene rearrangement, ROS1 rearrangement, rearranged during transfection (RET) rearrangement, NRTK1/2/3, gene fusion, BRAF V600E mutation, METex14 Skipping Mutation
• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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64 participants in 4 patient groups

Phase 1b Cohort 1: Bemcentinib Dose 1

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Bemcentinib

Drug: Carboplatin

Phase 1b Cohort 2: Bemcentinib Dose 2

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Bemcentinib

Drug: Carboplatin

Phase 1b Cohort 3: Bemcentinib Dose 3

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Bemcentinib

Drug: Carboplatin

Phase 2a Expansion Cohort: Bemcentinib (at 2 doses as determined from Phase 1b)

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Bemcentinib

Drug: Carboplatin