26 Participants Needed

Bemcentinib + Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 34 trial locations
BC
Overseen ByBerGenBio Clinical Team
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic treatment for their advanced/metastatic NSCLC.

What data supports the effectiveness of the drug combination Bemcentinib, Pembrolizumab, and Chemotherapy for Non-Small Cell Lung Cancer?

Research shows that combining pembrolizumab with chemotherapy, like carboplatin and pemetrexed, is effective in treating advanced non-small cell lung cancer, leading to longer survival times. This combination is now a standard first-line treatment, showing promising results in real-world studies.12345

Is the combination of Bemcentinib, Pembrolizumab, and Chemotherapy safe for humans?

The combination of pembrolizumab with chemotherapy drugs like pemetrexed and carboplatin has been studied for safety in non-small cell lung cancer, showing some side effects like pneumonitis (lung inflammation) in a small percentage of patients. Pemetrexed and carboplatin are generally well-tolerated, with less severe side effects compared to some other treatments.16789

What makes the Bemcentinib + Pembrolizumab + Chemotherapy treatment unique for non-small cell lung cancer?

This treatment is unique because it combines Bemcentinib, a novel drug, with Pembrolizumab and chemotherapy, which are already known to improve survival in non-small cell lung cancer. Bemcentinib may offer additional benefits by targeting specific cancer pathways, potentially enhancing the effectiveness of the existing combination.14101112

Eligibility Criteria

Adults with untreated advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that can't be cured by surgery or radiation, specifically those with STK11 mutation and no EGFR, ALK, ROS1, RET rearrangements, NRTK gene fusions, BRAF V600E or METex14 Skipping Mutations. Participants should not have had previous chemotherapy for their lung cancer.

Inclusion Criteria

Your doctor can measure your disease using specific guidelines.
My lung cancer is advanced or has spread, and cannot be cured with surgery.
My advanced non-small cell lung cancer is confirmed and cannot be cured with surgery.
See 1 more

Exclusion Criteria

My cancer has a specific genetic mutation or rearrangement.
I have had treatment for advanced lung cancer.
I had radiation therapy less than 2 weeks ago or still have side effects.
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bemcentinib with chemo-immunotherapy (CIT) as first line treatment for advanced/metastatic non-squamous NSCLC

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 26 months

Treatment Details

Interventions

  • Bemcentinib
  • Carboplatin
  • Pembrolizumab
  • Pemetrexed
Trial OverviewThe trial is testing the safety and effectiveness of Bemcentinib in combination with Pembrolizumab plus Pemetrexed and Carboplatin as a first-line treatment. The goal is to find the best dose for phase 2 trials and see how well this combo works against NSCLC with STK11 mutations.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -second as determined from Phase 1b)Experimental Treatment4 Interventions
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).
Group II: Phase 2a Expansion Cohort: Bemcentinib (at 2 doses -first as determined from Phase 1b)Experimental Treatment4 Interventions
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).
Group III: Phase 1b Cohort 3: Bemcentinib Dose 3Experimental Treatment4 Interventions
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).
Group IV: Phase 1b Cohort 2: Bemcentinib Dose 2Experimental Treatment4 Interventions
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).
Group V: Phase 1b Cohort 1: Bemcentinib Dose 1Experimental Treatment4 Interventions
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).

Find a Clinic Near You

Who Is Running the Clinical Trial?

BerGenBio ASA

Lead Sponsor

Trials
15
Recruited
900+

Findings from Research

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.
The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29).Renaud, E., Ricordel, C., Corre, R., et al.[2023]
In a real-world study of 54 patients with advanced non-squamous non-small cell lung cancer, the combination of carboplatin, pemetrexed, and pembrolizumab showed a higher disease control rate (86.7%) compared to carboplatin and pemetrexed alone (54%).
Patients with brain metastases treated with the combination therapy had a significantly lower progression rate (33.3%) compared to those receiving only carboplatin and pemetrexed (91.7%), indicating that this regimen may be particularly effective for this challenging patient group.
A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer.Afzal, MZ., Dragnev, K., Shirai, K.[2023]
In a study of 390 advanced non-squamous non-small cell lung cancer patients, first-line treatment with pemetrexed/carboplatin and bevacizumab (PemPBev) resulted in significantly better progression-free survival (7.5 months) and overall survival (18.6 months) compared to paclitaxel/carboplatin and bevacizumab (PacCBev) which had 6.2 months and 16.0 months respectively.
While the overall response rates and disease control rates were similar between the two treatments, PemPBev had a lower incidence of peripheral neuropathy compared to PacCBev (2.4% vs. 7.8%), suggesting it may be a safer option for patients.
First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.Chang, Q., Zhang, Y., Xu, J., et al.[2020]

References

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]
A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. [2023]
First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China. [2020]
PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. [2023]
Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]
Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. [2023]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]
Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]
Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]
12.United Statespubmed.ncbi.nlm.nih.gov
Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]