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

BerGenBio

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05469178

U1111-1312-8770 (Other Identifier)

2024 511007 41 00 (EU Trial (CTIS) Number)

BGBC016

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) 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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64 participants in 5 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: Bemcentinib

Drug: Pembrolizumab

Drug: Pemetrexed

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: Bemcentinib

Drug: Pembrolizumab

Drug: Pemetrexed

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: Bemcentinib

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first 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: Bemcentinib

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second 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 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).

Treatment:

Drug: Bemcentinib

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin