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 Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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) on Day 1 of each 21-day treatment cycle for a maximum of 4 cycles. After completion of the 4 cycles of CIT, participants will receive maintenance bemcentinib, pembrolizumab, and pemetrexed for up to 2 years. |
Drug: Bemcentinib
Bemcentinib capsules will be administered orally.
Biological: Pembrolizumab
Pembrolizumab will be administered as an IV infusion as part of CIT.
Drug: Pemetrexed
Pemetrexed will be administered as an IV infusion as part of CIT.
Drug: Carboplatin
Carboplatin will be administered as an IV infusion as part of CIT.
|
| 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) on Day 1 of each 21-day treatment cycle for a maximum of 4 cycles. After completion of the 4 cycles of CIT, participants will receive maintenance bemcentinib, pembrolizumab, and pemetrexed for up to 2 years. |
Drug: Bemcentinib
Bemcentinib capsules will be administered orally.
Biological: Pembrolizumab
Pembrolizumab will be administered as an IV infusion as part of CIT.
Drug: Pemetrexed
Pemetrexed will be administered as an IV infusion as part of CIT.
Drug: Carboplatin
Carboplatin will be administered as an IV infusion as part of CIT.
|
| 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) on Day 1 of each 21-day treatment cycle for a maximum of 4 cycles. After completion of the 4 cycles of CIT, participants will receive maintenance bemcentinib, pembrolizumab, and pemetrexed for up to 2 years. |
Drug: Bemcentinib
Bemcentinib capsules will be administered orally.
Biological: Pembrolizumab
Pembrolizumab will be administered as an IV infusion as part of CIT.
Drug: Pemetrexed
Pemetrexed will be administered as an IV infusion as part of CIT.
Drug: Carboplatin
Carboplatin will be administered as an IV infusion as part of CIT.
|
| Experimental: Phase 2a Expansion Cohort: Bemcentinib (at 2 doses as 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, 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) on Day 1 of each 21-day treatment cycle for a maximum of 4 cycles. After completion of the 4 cycles of CIT, participants will receive maintenance bemcentinib, pembrolizumab, and pemetrexed for up to 2 years. |
Drug: Bemcentinib
Bemcentinib capsules will be administered orally.
Biological: Pembrolizumab
Pembrolizumab will be administered as an IV infusion as part of CIT.
Drug: Pemetrexed
Pemetrexed will be administered as an IV infusion as part of CIT.
Drug: Carboplatin
Carboplatin will be administered as an IV infusion as part of CIT.
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of Participants with 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.
Secondary Outcome Measures
- Phase 1b: Objective Response Rate (ORR) [Up to 2 years]
ORR is defined as percentage of participants with complete response and partial response per RECIST 1.1.
- Phase 1b: Disease Control Rate (DCR) [Up to 2 years]
DCR is defined as percentage of participants with complete response, partial response and stable disease per RECIST 1.1.
- Phase 1b: Duration of Response (DOR) [Up to 2 years]
DOR is defined as time of first response to progressive disease as assessed per RECIST 1.1.
- Phase 1b: Overall Survival (OS) [Up to 2 years]
OS is defined as the time from randomization to death due to any cause.
- Phase 2a: Number of Participants with Adverse Events (AEs) [Up to 26 months]
An AE is any untoward medical occurrence in a patient or clinical study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
- Phase 2a: Number of Participants with Abnormalities in Safety Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) [Up to 26 months]
Number of participants with abnormalities in safety laboratory parameters (hematology, biochemistry, urinalysis, and coagulation parameters), vital signs (body temperature, pulse rate, seated diastolic and systolic blood pressure), and ECGs will be reported per CTCAE.
- Phase 2a: Disease Control Rate (DCR) [Up to 26 months]
DCR is defined as percentage of participants with complete response, partial response and stable disease per RECIST 1.1.
- Phase 2a: Duration of Response (DOR) [Up to 26 months]
DOR is defined as time of first response to progressive disease as assessed per RECIST 1.1.
- Phase 2a: Progression Free Survival (PFS) [Up to 26 months]
PFS is defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first.
- Phase 2a: Time to Progression (TTP) [Up to 26 months]
TTP is defined as the time from the first day of treatment to the first documented disease progression per RECIST 1.1.
- Phase 2a: Overall Survival (OS) [Up to 26 months]
OS is defined as the time from randomization to death due to any cause.
- Phase 2a: Observed Maximum Plasma Concentration After Single Dose Administration (Cmax) [Cycle 1 Day 1 pre-dose and 2- and 6-hours post-dose; Cycle 1 Day 2 pre-dose; Cycle 1 Day 8 pre-dose; and Cycle 1 Day 15 pre-dose. Cycle 1 duration= 21 days]
Cmax is defined as observed maximum plasma concentration after single dose administration.
- Phase 2a: Area Under the Curve Within a Dosing Interval (AUC[0-t]) [Cycle 1 Day 1 pre-dose and 2- and 6-hours post-dose; Cycle 1 Day 2 pre-dose; Cycle 1 Day 8 pre-dose; and Cycle 1 Day 15 pre-dose. Cycle 1 duration= 21 days]
AUC[0-t] is defined as area under the curve within a dosing interval, calculated by the linear up-log down trapezoidal method.
- Phase 2a: Apparent Terminal Half-life (t1/2) [Cycle 1 Day 1 pre-dose and 2- and 6-hours post-dose; Cycle 1 Day 2 pre-dose; Cycle 1 Day 8 pre-dose; and Cycle 1 Day 15 pre-dose. Cycle 1 duration= 21 days]
The apparent terminal half-life is calculated by 0.693/Lambda(z).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have a 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)
-
Have a 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. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease
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Have measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
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Have diagnostic/archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
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
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Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BerGenBio ASA
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGBC016
- 2019-003806-28