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

No longer recruiting at 36 trial locations

Overseen By BerGenBio Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BerGenBio ASA

Disqualifiers: Prior chemotherapy, Prior biological therapy, Recent radiation, Recent major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced non-small cell lung cancer (NSCLC) that cannot be surgically removed. The researchers aim to determine a safe dose of bemcentinib (an experimental treatment) when combined with chemotherapy and immunotherapy, and to assess whether this combination can shrink tumors. The trial includes different groups, each receiving slightly different doses of bemcentinib to identify the most effective one. Individuals who have not yet received treatment for their advanced NSCLC and have a specific gene mutation (STK11) may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining bemcentinib with pembrolizumab and chemotherapy is generally safe for patients. In earlier studies, many patients tolerated this combination without serious side effects. Bemcentinib blocks a protein that cancer cells need to grow, making lung cancer more responsive to pembrolizumab.

Common side effects include nausea and tiredness, but these are usually manageable. Serious side effects were rare. Pembrolizumab and the chemotherapy drugs, carboplatin and pemetrexed, are already approved treatments, so doctors are familiar with their side effects.

Overall, evidence suggests that this treatment is safe, but ongoing trials aim to find the best dose with the fewest side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about bemcentinib as part of the treatment for non-small cell lung cancer (NSCLC) because it offers a unique approach compared to standard therapies. Unlike traditional treatments that primarily target cancer cells directly, bemcentinib works by inhibiting a protein called AXL, which plays a role in helping cancer cells evade the immune system. This mechanism could potentially enhance the effectiveness of immunotherapy drugs like pembrolizumab. Additionally, using bemcentinib in combination with chemotherapy may offer a more comprehensive attack on cancer, potentially improving outcomes for patients with advanced NSCLC.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Studies have shown that combining pembrolizumab with chemotherapy drugs like carboplatin and pemetrexed effectively treats advanced non-small cell lung cancer (NSCLC). In this trial, participants will receive varying doses of bemcentinib, an AXL inhibitor, alongside pembrolizumab, carboplatin, and pemetrexed. Research suggests that bemcentinib can help overcome chemotherapy resistance and enhance tumor response, particularly in patients with the STK11 gene mutation. This makes bemcentinib a promising addition to cancer treatment. Early results indicate that these drug combinations could improve outcomes for patients with advanced NSCLC. By blocking certain pathways, bemcentinib inhibits cancer cell growth, potentially enhancing the effectiveness of other treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bemcentinib
• Carboplatin
• Pembrolizumab
• Pemetrexed

Trial Overview The 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.

How Is the Trial Designed?

Group I: Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b) Experimental Treatment 4 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 1b Cohort 3: Bemcentinib 150 mg Experimental Treatment 4 Interventions

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).

Group III: Phase 1b Cohort 2: Bemcentinib 100 mg Experimental Treatment 4 Interventions

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).

Group IV: Phase 1b Cohort 1: Bemcentinib 75 mg Experimental Treatment 4 Interventions

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).

Who Is Running the Clinical Trial?

BerGenBio ASA

Lead Sponsor

Trials

15

Recruited

900+

Published Research Related to This Trial

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Isla, D., Sánchez, A., Casal, J., et al.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

The combination of pemetrexed, platinum, and pembrolizumab shows manageable toxicity, with most severe adverse events occurring early in treatment and resolving within two weeks, indicating a favorable safety profile for long-term use.

While there was a slightly higher incidence of renal toxicity in patients receiving the pembrolizumab combination compared to those on pemetrexed alone, this did not increase with longer treatment durations, supporting the regimen's safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. Garon, EB., Aerts, J., Kim, JS., et al.[2023]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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bemcentinib (BGB324) Trials NCT02922777: Trial of Dose Escalated BGB324 in Previously Treated Non-small Cell Lung Cancer. Completed. 1. 23. US. BGB324, Docetaxel, Taxotere. University of ...

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7. jto.org jto.org/article/S1556-0864(23)00332-5/pdf

78TiP Phase Ib/IIa safety and tolerability ... Bemcentinib (BEM), a selective AXL inhibitor, has been shown in preclinical studies to sensitize STK11m NSCLC to pembrolizumab. Therefore, the addition of BEM ...