Dose Escalation Trial of Bexmarilimab (FP-1305) Plus Pembrolizumab in Non-Small Cell Lung Cancer

Overseen By Epp Goodwin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Pembrolizumab

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: CNS metastases, Serious infection, others

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

Compensation: Varies

Number of Visits: 3

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any immunotherapy in the three weeks before starting the trial, and you should not be on systemic corticosteroids or other immunosuppressive treatments.

What data supports the effectiveness of the drug pembrolizumab (KEYTRUDA) in treating cancer?

Pembrolizumab has shown effectiveness in treating advanced melanoma and non-small cell lung cancer by helping the immune system attack cancer cells. It has been approved for use in patients with melanoma who have not responded to other treatments, and studies have shown it can lead to prolonged tumor responses. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been studied in various clinical trials and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects like pneumonitis (lung inflammation) and colitis (inflammation of the colon) can occur in some patients. ^{1 2 3 6 7}

What makes the drug combination of Bexmarilimab and Pembrolizumab unique?

The combination of Bexmarilimab and Pembrolizumab is unique because it involves using Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, which has shown effectiveness in various cancers. Bexmarilimab is a novel component that may enhance this effect, although specific details about its mechanism in this combination are not provided in the available research. ^{1 5 6 8 9}

What is the purpose of this trial?

This trial tests a new drug, Bexmarilimab, combined with Pembrolizumab, in patients with non-small cell lung cancer. The goal is to see if this combination is safe and can help the immune system fight cancer by blocking a specific receptor. The study will increase the dose over time to find the highest safe amount.

Research Team

Supreet Kaur, MD

Principal Investigator

UT Health San Antonio

Eligibility Criteria

Inclusion Criteria

Women of child-bearing potential must have a negative pregnancy test prior to trial entry and cycle 1 day 1 and should not be breast feeding.

Able to provide written Informed Consent

Tumor sample obtained less than six months from the date of consent

Exclusion Criteria

Pregnant or lactating women

Any condition that study investigators consider an impediment to safe trial participation

Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than five half-lives from a small molecule targeted therapy or oral anticancer chemotherapy before the first bexmarilimab administration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Treatment

Participants receive Bexmarilimab plus Pembrolizumab in a 3+3 dose escalation format to determine the maximum tolerated dose

12 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Bexmarilimab (FP-1305)
• Pembrolizumab

Participant Groups

Group I: Cohort 4 Experimental Treatment 2 Interventions

Study participants will receive 30 mg/kg Bexmarilimab plus pembrolizumab 200mg IV once every 3 weeks.

Group II: Cohort 3 Experimental Treatment 2 Interventions

Study participants will receive 10 mg/kg Bexmarilimab plus pembrolizumab 200mg IV once every 3 weeks. 3 participants will need to complete this level before the next cohort dosing begins.

Group III: Cohort 2 Experimental Treatment 2 Interventions

Study participants will receive 3mg/kg Bexmarilimab given in combination with Pembrolizumab 200mg IV once every three weeks. 3 participants will need to complete this level before the next cohort dosing begins.

Group IV: Cohort 1 Experimental Treatment 2 Interventions

Study patients will receive 0.1-1 mg/kg bexmarilimab (FP-1350) given in combination with Pembrolizumab 200mg IV once every three weeks. The first subject will be started on 0.1mg to establish toleration, for one dose, and then the dose will be escalated to 1mg. This subject will be included in Cohort 1 data.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Faron Pharmaceuticals Ltd

Industry Sponsor

Trials

9

Recruited

780+

Findings from Research

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 study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

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]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]