REGN7075 + Cemiplimab for Advanced Cancer

(COMBINE-EGFR-1 Trial)

Recruiting at64 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Second malignancy, Brain tumor, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called REGN7075, alone or with other treatments, on patients with advanced solid tumors. The goal is to see if it can stop tumor growth and shrink the tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as any approved systemic therapy, recent anti-EGFR antibody therapy, or previous systemic non-immunomodulatory biologic therapy within 4 weeks of the study drug. If you're on corticosteroids, you may need to stop or reduce them 1-2 weeks before starting the trial.

What data supports the effectiveness of the drug Cemiplimab in treating advanced cancer?

Cemiplimab has shown effectiveness in treating advanced non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma by blocking a protein that helps cancer cells hide from the immune system. It has been approved for use in these cancers, indicating its potential effectiveness in other advanced cancers. ^{1 2 3 4 5}

Is the combination of REGN7075 and Cemiplimab safe for humans?

Cemiplimab, also known as Libtayo, has been shown to have an acceptable safety profile in clinical trials for advanced cutaneous squamous cell carcinoma, with most side effects being manageable. However, specific safety data for the combination of REGN7075 and Cemiplimab is not provided in the available research. ^{1 4 6 7 8}

What makes the drug REGN7075 + Cemiplimab unique for treating advanced cancer?

This treatment combines cemiplimab, a drug that blocks a protein called PD-1 to help the immune system attack cancer cells, with REGN7075, a bispecific antibody that targets EGFR and CD28 to enhance immune response. This combination aims to provide a novel approach by simultaneously blocking cancer cell defenses and boosting immune activation, which is different from standard treatments that typically target only one pathway. ^{1 2 4 7 9}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

Adults with advanced solid tumors who have never been treated with PD-1/PD-L1 inhibitors, have a measurable lesion, are in good physical condition (ECOG 0 or 1), and can provide a new tumor tissue sample. They must not be on other clinical trials, haven't had certain treatments recently, don't have brain tumors or CNS issues, no significant autoimmune disease requiring immunosuppressants, and no second active cancer.

Inclusion Criteria

I am willing to provide a new biopsy sample from a tumor that hasn't been treated with radiation.

In the judgement of the investigator, has a life expectancy of at least 3 months

I have never been treated with drugs targeting PD-1/PD-L1.

Exclusion Criteria

I have a current skin condition that causes inflammation.

Has participated in any study of an investigational agent or an investigational device within 4 weeks of the first administration of study drug as defined in the protocol

I haven't had any non-immunomodulatory biologic therapy in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of REGN7075 to determine the maximum tolerated dose

Up to 6 weeks

Dose Expansion

Participants receive the determined dose of REGN7075 in combination with cemiplimab, with or without chemotherapy, to evaluate safety and efficacy

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 90 days from last dose

Treatment Details

Interventions

• Cemiplimab (Monoclonal Antibodies)
• REGN7075 (Monoclonal Antibodies)

Trial Overview The trial is testing REGN7075 alone and combined with cemiplimab plus/minus chemotherapy to determine safety, tolerability, optimal dosing levels for advanced solid tumors treatment effectiveness by observing the control of tumor cell growth and shrinkage.

Participant Groups

Group I: Dose Expansion J Experimental Treatment 4 Interventions

3L MSS-CRC without Active Liver Metastases

Group II: Dose Expansion I Experimental Treatment 4 Interventions

Third-line (3L) MSS-CRC with Active Liver Metastases

Group III: Dose Expansion H Experimental Treatment 2 Interventions

EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy

Group IV: Dose Expansion G Experimental Treatment 3 Interventions

Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)

Group V: Dose Expansion F Experimental Treatment 2 Interventions

MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)

Group VI: Dose Expansion E Experimental Treatment 2 Interventions

Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases

Group VII: Dose Expansion D Experimental Treatment 2 Interventions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Group VIII: Dose Expansion C Experimental Treatment 3 Interventions

Non-Small Cell Lung Cancer (NSCLC)

Group IX: Dose Expansion B Experimental Treatment 2 Interventions

Cutaneous Squamous Cell Carcinoma (CSCC)

Group X: Dose Expansion A Experimental Treatment 2 Interventions

Triple Negative Breast Cancer (TNBC)

Group XI: Dose Escalation Experimental Treatment 2 Interventions

Variety of mixed advanced solid tumor types

Cemiplimab is already approved in Canada, Brazil for the following indications:

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

Cemiplimab, an anti-PD-1 monoclonal antibody, demonstrated a favorable safety profile in a study of 60 patients with advanced solid tumors, with no dose-limiting toxicities and manageable treatment-emergent adverse events like fatigue and nausea.

The treatment showed promising antitumor activity, with 2 complete responses and 7 partial responses, and responses lasting at least 12 months in some patients, indicating its potential effectiveness when combined with hypofractionated radiotherapy and/or cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Papadopoulos, KP., Johnson, ML., Lockhart, AC., et al.[2021]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

In a phase 2 study involving 80 chemotherapy-naïve patients with advanced nonsmall cell lung cancer (NSCLC), the combination of cetuximab, carboplatin, and docetaxel showed a modest objective response rate of 15.2% and a median overall survival of 10.3 months.

The treatment was generally well tolerated, with significant adverse events including neutropenia (30%), but patients who continued on single-agent cetuximab after initial treatment experienced manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Belani, CP., Schreeder, MT., Steis, RG., et al.[2019]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

Cemiplimab, a PD-1 inhibitor, demonstrated an objective response rate of 25% in patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone treatment, indicating its potential effectiveness in this challenging patient population.

The treatment was generally well-tolerated, although 60% of patients experienced severe treatment-emergent adverse events, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. Moreno, V., Garrido, P., Papadopoulos, KP., et al.[2021]

References

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

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. [2023]

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

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. [2021]

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

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. [2022]

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

Cemiplimab: First Global Approval. [2023]

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

Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. [2019]

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

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

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

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

9. Ireland pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. [2021]