Bemarituzumab Combination Therapy for Squamous Cell Lung Cancer

(FORTITUDE-201 Trial)

Recruiting at 44 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Anti-arrhythmics, FGF-FGFR inhibitors

Disqualifiers: Mixed lung cancer, CNS metastases, cardiac disease, others

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

Compensation: Varies

Number of Visits: 21

Duration: 6.2 weeks

74 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests bemarituzumab, a cancer treatment, alone or with other therapies. It aims to check its safety in cancer patients and find the best dose. Bemarituzumab works by attaching to cancer cells and blocking their growth.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Bemarituzumab Combination Therapy for Squamous Cell Lung Cancer?

Research shows that albumin-bound paclitaxel (nab-paclitaxel), a component of the combination therapy, has shown promising results in improving outcomes for patients with advanced non-small-cell lung cancer (NSCLC), which is a similar type of lung cancer. Studies have demonstrated its effectiveness and safety when used with carboplatin, another component of the therapy. ^{1 2 3 4 5}

Is Bemarituzumab combination therapy safe for humans?

Research shows that treatments like pembrolizumab (KEYTRUDA) and nanoparticle albumin-bound paclitaxel (Abraxane) have been studied for safety in lung cancer patients. These studies found that the treatments generally have an acceptable safety profile, meaning they are considered safe for use in humans, although they can have side effects like any medication. ^{2 6 7 8 9}

What makes the Bemarituzumab combination therapy unique for squamous cell lung cancer?

The Bemarituzumab combination therapy is unique because it includes nab-paclitaxel, an albumin-bound form of paclitaxel, which improves drug concentration in tumors and has shown better response rates in squamous cell lung cancer compared to traditional solvent-based paclitaxel. This combination also includes pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, offering a novel approach by combining chemotherapy with immunotherapy. ^{1 4 5 10 11}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults with a specific lung cancer type (SqNSCLC) that can't be removed by surgery or has spread, and shows high levels of FGFR2b protein. Participants must have tried at least one systemic therapy before, unless they're in Part 4 where no prior treatment for advanced disease is allowed. They need good organ function and an ECOG status of 0 or 1, meaning they are fully active or restricted in physically strenuous activity but can do light work.

Inclusion Criteria

My organs are working well.

I have a tumor tissue sample from the last 5 years or am willing to provide one.

I haven't had systemic therapy for my advanced or metastatic disease yet.

Exclusion Criteria

My cancer got worse after treatment with docetaxel.

I have had docetaxel for advanced cancer but not as an early treatment that didn't progress quickly.

I have serious heart issues, including recent heart attacks or uncontrolled blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bemarituzumab monotherapy or in combination with other anti-cancer therapies

6.2 weeks

Visits every 21 days for Parts 1, 2, and 4; every 14 days for Part 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after the last dose

Long-term Follow-up

Participants are monitored for survival and disease progression

Every 3 months ± 1 month after the safety follow-up visit, up to the end of the study

Treatment Details

Interventions

• Bemarituzumab
• Carboplatin
• Docetaxel
• Nab-paclitaxel
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests Bemarituzumab alone and combined with other anti-cancer drugs like Docetaxel, Pembrolizumab, Carboplatin, Paclitaxel, Nab-paclitaxel to find the safest dose for phase 3 trials. It's checking how well patients tolerate these treatments and what effects they have on this type of lung cancer.

Participant Groups

Group I: Part 4: Combination Immuno-chemotherapy Experimental Treatment 5 Interventions

Participants with FGFR2b overexpression will receive the dose of bemarituzumab identified as safe during Part 1 in combination with pembrolizumab, carboplatin and either paclitaxel or nab-paclitaxel.

Group II: Part 3: Bemarituzumab Monotherapy Experimental Treatment 1 Intervention

Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.

Group III: Part 2: Combination Dose Expansion Experimental Treatment 2 Interventions

Participants with SqNSCLC and FGFR2b overexpression will receive the dose of bemarituzumab in combination with docetaxel identified as safe during Part 1.

Group IV: Part 1: Combination Dose Exploration Experimental Treatment 2 Interventions

Participants with SqNSCLC will receive escalating doses of bemarituzumab in combination with docetaxel.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

A phase 3 study (J-AXEL) is underway to compare the efficacy and safety of nab-paclitaxel to docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC), involving randomization of patients to receive either treatment until disease progression or unacceptable toxicity.

The primary goal of the study is to demonstrate that nab-paclitaxel is noninferior to docetaxel in terms of overall survival, which could establish nab-paclitaxel as a new treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. Yoneshima, Y., Morita, S., Ando, M., et al.[2018]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

In a study of 21 patients with recurrent advanced non-small-cell lung cancer (NSCLC), albumin-bound paclitaxel (ABP) monotherapy resulted in a partial response in 28.6% of patients and a disease control rate of 76.2%.

The treatment was generally well tolerated, with manageable side effects, including neutropenia in 11.1% of patients, indicating that ABP can be a viable option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer. Xing, PY., Li, JL., Wang, Y., et al.[2021]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel. [2018]

4. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer. [2018]

11. China 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). [2023]