Carcinoma, Non-Small-Cell Lung
Conditions
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.
Interventions
DRUGBemcentinib
Bemcentinib capsules will be administered daily orally.
DRUGPembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion as part of CIT every 3 weeks.
DRUGPemetrexed
Pemetrexed will be administered as an IV infusion as part of CIT every 3 weeks.
DRUGCarboplatin
Carboplatin will be administered as an IV infusion as part of CIT every 3 weeks up to 4 cycles. Each cycle = 21 days.
Sponsors
BerGenBio ASA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) | Cycle 1 (the first 21 days of treatment) | DLT 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. |
Countries
France, Greece, Hungary, Italy, Poland, Spain, United States
Participant flow
Recruitment details
Study recruitment was undertaken across 7 planned countries: USA, France, Greece, Hungary, Italy, Poland & Spain. Of these countries, 5 countries enrolled participants: USA (10 participants), France (5 participants), Greece (3 participants), Italy (2 participants) & Spain (6 participants). The recruitment process began in March 2023 and concluded in February 2025. 65 participants were screened in order to successfully recruit 26 participants.
Pre-assignment details
Participants were screened to the inclusion/exclusion criteria of the protocol. The following assessments were performed: Informed Consent, Demographics, Medical/Surgical History including NSCLC diagnosis and prior anticancer treatments, Pregnancy/FSH, ECOG performance score, Vital signs, Physical examination, Echocardiogram, Laboratory Safety Testing, ECG, Tumour imaging/sampling and biopsies & blood sampling for genomic DNA/serum biomarkers.
Participants by arm
| Arm | Count |
|---|---|
| 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 received oral bemcentinib 75 mg once daily until a reason for discontinuation had been met or for up to 2 years, whichever occurred first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin). CIT was administered on day 1 of 21-day cycles via intravenous (IV) infusions and comprised pembrolizumab, pemetrexed, and carboplatin. Carboplatin was administered for a maximum of 4 cycles only. | 3 |
| 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 received oral bemcentinib 100 mg once daily until a reason for discontinuation had been met or for up to 2 years, whichever occurred first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin). CIT was administered on day 1 of 21-day cycles via intravenous (IV) infusions and comprised pembrolizumab, pemetrexed, and carboplatin. Carboplatin was administered for a maximum of 4 cycles only. | 3 |
| 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 received oral bemcentinib 150 mg once daily until a reason for discontinuation had been met or for up to 2 years, whichever occurred first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin). CIT was administered on day 1 of 21-day cycles via intravenous (IV) infusions and comprised pembrolizumab, pemetrexed, and carboplatin. Carboplatin was administered for a maximum of 4 cycles only. | 4 |
| Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the Dose 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). CIT was administered on day 1 of 21-day cycles via intravenous (IV) infusions and comprised pembrolizumab, pemetrexed, and carboplatin. Carboplatin was administered for a maximum of 4 cycles only. | 16 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 3 | 6 |
| Overall Study | Lack of Efficacy | 2 | 2 | 1 | 10 |
Baseline characteristics
| Characteristic | Phase 1b Cohort 2: Bemcentinib 100 mg | Phase 1b Cohort 1: Bemcentinib 75 mg | Total | Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the Dose Determined From Phase 1b) | Phase 1b Cohort 3: Bemcentinib 150 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 13 Participants | 7 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 13 Participants | 9 Participants | 2 Participants |
| Age, Continuous | 71.0 Years STANDARD_DEVIATION 3.46 | 52.0 Years STANDARD_DEVIATION 26.66 | 62.4 Years STANDARD_DEVIATION 15.46 | 61.2 Years STANDARD_DEVIATION 11.67 | 63.8 Years STANDARD_DEVIATION 7.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 5 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 15 Participants | 13 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 6 Participants | 1 Participants | 3 Participants |
| Height | 165.00 Centimetres | 172.00 Centimetres | 171.50 Centimetres | 171.00 Centimetres | 173.00 Centimetres |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 21 Participants | 14 Participants | 4 Participants |
| Region of Enrollment France | 1 participants | 1 participants | 5 participants | 0 participants | 3 participants |
| Region of Enrollment Greece | 0 participants | 0 participants | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Italy | 0 participants | 0 participants | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 6 participants | 6 participants | 0 participants |
| Region of Enrollment United States | 2 participants | 2 participants | 10 participants | 5 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 5 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 21 Participants | 13 Participants | 4 Participants |
| Weight | 82.00 Kilograms | 75.30 Kilograms | 73.75 Kilograms | 70.50 Kilograms | 71.30 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 3 / 4 | 6 / 16 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 15 / 16 |
| serious Total, serious adverse events | 2 / 3 | 3 / 3 | 1 / 4 | 6 / 16 |
Outcome results
Primary
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
DLT graded using NCI CTCAE Version 5.0 based on the Investigator assessment.
Time frame: Cycle 1 (the first 21 days of treatment)
Population: This analysis population included all 10 participants who were enrolled into Phase 1b of the study and completed at least one cycle of treatment for evaluation of DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort 1: Bemcentinib 75 mg | Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1b Cohort 2: Bemcentinib 100 mg | Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1b Cohort 3: Bemcentinib 150 mg | Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
Primary
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.
Time frame: 12 months
Population: This analysis population included all 16 participants who were enrolled into Phase 2a of the study and completed sufficient cycles of treatment up to the 12-month timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort 1: Bemcentinib 75 mg | Phase 2a: Objective Response Rate (ORR) at 12 Months | 0 Participants |
Primary
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.
Time frame: 6 months
Population: This analysis population included all 16 participants who were enrolled into Phase 2a of the study and completed sufficient cycles of treatment up to the 6-month timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort 1: Bemcentinib 75 mg | Phase 2a: Objective Response Rate (ORR) at 6 Months | 0 Participants |