REGN7075 + Cemiplimab for Advanced Cancer

(COMBINE-EGFR-1 Trial)

Recruiting at 81 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Second malignancy, Brain tumor, others

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

Compensation: Varies

Number of Visits: Unknown

933 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, REGN7075 (an EGFRxCD28 costimulatory bispecific antibody), both alone and with cemiplimab (also known as Libtayo), to determine their effectiveness in treating certain advanced solid tumors. Researchers aim to identify the safest and most effective dose of REGN7075, either alone or with cemiplimab, and to understand its mechanism in the body and its side effects. Individuals with certain advanced cancers, such as specific lung or breast cancers, who have not previously received PD-1/PD-L1 drugs, may qualify. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that REGN7075, when combined with cemiplimab, demonstrates promising safety results. In earlier studies, no patients experienced serious side effects that limited the dose, indicating the treatment was well-tolerated at the tested amounts. Cemiplimab, already approved for some cancers, has a known safety record. Serious side effects occurred in about 25% of patients, similar to other cancer treatments. Overall, these findings suggest that both REGN7075 and cemiplimab are generally well-tolerated, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cemiplimab and REGN7075 for advanced cancer because they work in a unique way compared to standard treatments. Cemiplimab is an immune checkpoint inhibitor that unleashes the body's T-cells to attack cancer by blocking the PD-1 pathway, a mechanism not used by traditional chemotherapy. REGN7075 is an innovative bispecific antibody that connects T-cells directly to cancer cells, potentially enhancing the immune attack. This combination could offer a more targeted and robust approach to fighting various types of cancer, including those that are resistant to current therapies.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that REGN7075, a new type of antibody, may help treat tumors that typically resist the immune system. Participants in this trial may receive REGN7075, which has shown promise in treating a challenging type of colorectal cancer, even when it has metastasized to the liver. Another treatment option in this trial is cemiplimab, which past studies have found to shrink tumors. Specifically, cemiplimab completely eliminated tumors in 20% of patients and reduced them in 27% of patients with advanced cancers. This trial will explore combining REGN7075 with cemiplimab to enhance the immune system's response to advanced solid tumors, offering hope for improved treatment outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• REGN7075

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

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

Approved in United States as Libtayo for:

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

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

Published Research Related to This Trial

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 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]

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]

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, 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]

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]

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 (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]

Citations

1.

newsroom.regeneron.com

newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ...

Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40075670/

Effectiveness and Toxicity of Cemiplimab Therapy for ...

Results: Of the 36 patients treated, 22 (61.1%) achieved complete remission, 10 (27.8%) experienced a partial response, 3 (8.3%) had stable ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9533

CemiplimAb-rwlc survivorship and epidemiology (CASE)

Median PFS was 14.7 (95% CI: 12.5, 21.1) months, with survival at 12 months estimated at 59.5% (95% CI: 51.4, 66.7). Treatment-related irAEs ...

4.

libtayo.com

libtayo.com/cscc/why-libtayo

Taking LIBTAYO® (cemiplimab-rwlc) | Advanced CSCC

LIBTAYO study results · 15 out of 56 patients (27%) saw tumors shrink (partial response) · 11 out of 56 patients (20%) saw tumors disappear completely (complete ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772611823000071

Real-world data on tolerability and clinical response of ...

Cemiplimab demonstrated to be well-tolerated, even in elderly patients with severe comorbidities, achieving an objective response in 52% of patients.

6.

libtayohcp.com

libtayohcp.com/nsclc

LIBTAYO® (cemiplimab-rwlc) in Advanced NSCLC

Safety Data 1,2. Serious adverse reactions occurred in 25% of patients. The ... advanced non-small cell lung cancer (NSCLC). Ann Oncol. 2021;32(suppl 5): ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2023/761097s016lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use

Study 1423. In 26 patients with advanced CSCC treated with LIBTAYO in Study 1423 [see Clinical Studies. (14.1)], safety data were consistent with those ...

8.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/libtayo

Libtayo | European Medicines Agency (EMA)

Libtayo is a cancer medicine used in adults to treat: a type of skin cancer called cutaneous squamous cell carcinoma when the cancer is locally advanced (has ...

9.

libtayohcp.com

libtayohcp.com/

LIBTAYO® (cemiplimab-rwlc) | Official HCP Website

LIBTAYO as a single agent is indicated for the first-line treatment of adult patients with NSCLC whose tumors have high PD-L1 expression (tumor proportion score ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10936461/

High response rate with extended dosing of cemiplimab in ...

11 Herein, we report the final analysis of the efficacy and safety data with the extended dosing regimen of intravenous cemiplimab 600 mg Q4W ( ...