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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Bemcentinib
* Drug: Pembrolizumab
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b Cohort 1: Bemcentinib Dose 1<br>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). | Drug: Bemcentinib<br>* Bemcentinib capsules will be administered orally.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Carboplatin<br>* Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks.<br>|
| Experimental: Phase 1b Cohort 2: Bemcentinib Dose 2<br>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). | Drug: Bemcentinib<br>* Bemcentinib capsules will be administered orally.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Carboplatin<br>* Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks.<br>|
| Experimental: Phase 1b Cohort 3: Bemcentinib Dose 3<br>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). | Drug: Bemcentinib<br>* Bemcentinib capsules will be administered orally.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Carboplatin<br>* Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks.<br>|
| Experimental: Phase 2a Expansion Cohort: Bemcentinib (at 2 doses as determined from Phase 1b)<br>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). | Drug: Bemcentinib<br>* Bemcentinib capsules will be administered orally.<br>Drug: Pembrolizumab<br>* Pembrolizumab will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.<br>Drug: Carboplatin<br>* Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT) | DLT will be graded using NCI CTCAE Version 5.0 based on the Investigator assessment. | Cycle 1 (the first 21 days of treatment) | 
| 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 |