REGN5093-M114 for Non-Small Cell Lung Cancer

No longer recruiting at 20 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Other malignancy, Untreated brain tumor, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, REGN5093-M114 (a METxMET Antibody-Drug Conjugate), for treating advanced non-small cell lung cancer (NSCLC) with excess MET protein on cancer cells. The goal is to determine a safe dose and assess whether the drug can effectively shrink tumors, either alone or with another drug, cemiplimab. The study seeks participants with advanced NSCLC who have no other treatment options and whose tumors overproduce the MET protein. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received any approved systemic therapy or participated in another study within 2 weeks or 5 half-lives of the prior treatment, whichever is shorter, with a minimum of 7 days from the first dose of the study therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any approved systemic therapy or participated in another study within 2 weeks or 5 half-lives of the prior treatment, whichever is shorter, with a minimum of 7 days from the first dose of the study therapy.

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

Research has shown that REGN5093-M114, when used alone, is well-tolerated in early tests. Preclinical studies demonstrated strong tumor activity and general safety in animals, such as monkeys, at certain doses. This suggests potential safety for humans, though further testing is necessary for confirmation.

Researchers are also examining the safety of combining REGN5093-M114 with cemiplimab. Cemiplimab, already approved for other conditions, is generally considered safe. However, this combination requires thorough testing to ensure it doesn't cause unexpected issues. Both aspects of this study are crucial for understanding the safety of these treatments for individuals with advanced non-small cell lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

REGN5093-M114 is unique because it targets specific proteins on cancer cells, offering a novel approach to treating non-small cell lung cancer. Unlike traditional chemotherapy that attacks all rapidly dividing cells, REGN5093-M114 zeroes in on the MET protein, which is often involved in cancer growth. Researchers are excited about this treatment because it can be used alone or combined with cemiplimab, an immunotherapy drug that helps the immune system better identify and destroy cancer cells. This targeted strategy not only promises to be more effective but may also reduce the side effects typically associated with broader cancer treatments.

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

Research has shown that REGN5093-M114, a special type of treatment, may help fight non-small cell lung cancer (NSCLC) with high levels of a protein called MET. This trial includes arms where participants receive REGN5093-M114 as monotherapy, which appears effective against cancer cells, especially when other treatments have failed. Another arm of this trial studies the combination of REGN5093-M114 with cemiplimab, a drug that boosts the immune system. Lab studies have demonstrated strong cancer-fighting effects with this combination, aiming to help the immune system better attack cancer cells. Overall, early results are promising, but further research is needed to confirm these findings in people. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) that overexpresses MET protein. Participants must be in good physical condition (ECOG 0 or 1), have proper organ and bone marrow function, and provide a recent tumor tissue sample. Those who've had certain treatments or surgeries recently, active brain tumors, uncontrolled infections like HIV/Hepatitis B/C, or other progressing cancers aren't eligible.

Inclusion Criteria

I am willing to provide a recent or new biopsy of my tumor for testing.

My lung cancer is at an advanced stage with no other beneficial treatments available.

I have at least one tumor that can be measured and has grown after radiation.

Exclusion Criteria

I haven't had any cancer treatment or been in a trial for at least 2 weeks.

I do not have an active brain tumor or cancer spread to my brain or spinal cord.

I haven't had major surgery or radiation within the last 14 days and have recovered from any side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine a safe dose of REGN5093-M114 and in combination with cemiplimab

Up to 28 days

Dose Expansion

Use the determined dose to evaluate the effectiveness of the study drug in shrinking tumors

Through study completion, an average of 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REGN5093-M114

Trial Overview The trial is testing REGN5093-M114, an antibody-drug conjugate targeting MET-overexpressing cancer cells. Phase 1 determines the safest dose with acceptable side effects; phase 2 tests how well it works against NSCLC by measuring tumor response rates.

How Is the Trial Designed?

Group I: Phase 2. Dose Expansion Experimental Treatment 2 Interventions

Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.

Group II: Phase 1. Dose Escalation Experimental Treatment 2 Interventions

Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.

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

REGN5093-M114, a novel antibody-drug conjugate targeting MET, showed significant antitumor efficacy in preclinical models of EGFR-mutant non-small cell lung cancer (NSCLC), outperforming traditional MET TKIs.

The treatment was effective regardless of MET gene copy number and was particularly potent in reducing tumor growth in cases with PTEN loss or MET Y1230C mutation, suggesting it could be a valuable option for patients who have developed resistance to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC. Oh, SY., Lee, YW., Lee, EJ., et al.[2023]

The METxMET-M114 antibody-drug conjugate (ADC) shows significant and lasting tumor regression in models of lung cancer with high MET expression, including those resistant to existing MET-targeted therapies.

In a toxicology study on cynomolgus monkeys, METxMET-M114 was well tolerated at effective doses, indicating its potential safety and efficacy for treating MET-overexpressing tumors in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade. DaSilva, JO., Yang, K., Surriga, O., et al.[2023]

Telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, showed a low response rate of only 9% in patients with c-MET-positive squamous cell carcinoma, leading to the early closure of the study due to lack of efficacy.

The treatment was associated with significant toxicities, including three grade 5 adverse events, notably pneumonitis, highlighting safety concerns in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753). Waqar, SN., Redman, MW., Arnold, SM., et al.[2022]

Antibody Drug Conjugates (ADCs) are a promising new treatment for various cancers, including lung cancer, as they combine an antibody targeting tumor cells with a powerful cytotoxic drug.

Trastuzumab Deruxtecan (T-DXd) is the first ADC approved by the FDA for lung cancer, showing significant effectiveness in tumors with HER2 mutations based on results from the Destiny-Lung01 and Lung02 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress. Rosner, S., Valdivia, A., Hoe, HJ., et al.[2023]

In a study of 23 patients with advanced HER2-expressing solid tumors, RC48-antibody-drug conjugate (ADC) demonstrated a promising objective response rate (ORR) of 43.5% and a median progression-free survival (PFS) of 6.0 months, indicating its potential effectiveness in this patient population.

The treatment was generally well-tolerated, with manageable adverse events such as anemia and leukopenia, and no Grade 4 adverse reactions or deaths reported, suggesting a favorable safety profile for RC48-ADC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RC48-ADC treatment for patients with HER2-expressing locally advanced or metastatic solid tumors: a real-world study. Wang, P., Xia, L.[2023]

SGN-B6A is an antibody-drug conjugate specifically targeting integrin beta-6, which is overexpressed in various solid tumors and associated with poor prognosis, showing promising preclinical efficacy in models of non-small cell lung, pancreatic, pharyngeal, and bladder cancers.

In nonclinical studies, SGN-B6A was well-tolerated in cynomolgus monkeys at doses up to 6 mg/kg, with dose-limiting hematologic toxicities but no significant target-mediated toxicity, paving the way for a phase I clinical trial to assess its safety and effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. Lyon, RP., Jonas, M., Frantz, C., et al.[2023]

Antibody-drug conjugates (ADCs) represent a promising new class of cancer treatment for advanced non-small cell lung cancer (NSCLC) by delivering cytotoxic drugs directly to tumor cells, combining the benefits of chemotherapy and targeted therapy.

The review highlights the clinical development of various ADCs targeting both established and novel antigens, and discusses potential strategies, including combinations with other therapies, to overcome resistance mechanisms in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody drug conjugates in non-small cell lung cancer: An emerging therapeutic approach. Marks, S., Naidoo, J.[2022]

Antibody Drug Conjugates (ADCs) are innovative cancer treatments that combine antibodies with potent cytotoxic agents, with nine already approved by the FDA and many more in development, including for non-cancer uses.

Despite their potential, ADCs face challenges like off-target toxicity and a narrow therapeutic index, highlighting the need for improved targeting strategies and specific safety evaluation guidelines tailored to ADCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo safety testing of Antibody Drug Conjugates. Pretto, F., FitzGerald, RE.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04982224

NCT04982224 | Study of REGN5093-M114 (METxMET ... This study is researching an experimental drug called REGN5093-M114 by itself and in combination with cemiplimab. The study is focused on advanced non-small ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36269795/

Preclinical Study of a Biparatopic METxMET Antibody-Drug ... Results: REGN5093-M114 exhibited significant antitumor efficacy compared with MET TKI or unconjugated METxMET biparatopic antibody (REGN5093).

3. withpower.com withpower.com/trial/phase-2-7-2021-cd031

REGN5093-M114 for Non-Small Cell Lung Cancer REGN5093-M114, a novel antibody-drug conjugate targeting MET, showed significant antitumor efficacy in preclinical models of EGFR-mutant non-small cell lung ...

4. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/novel-regeneron-bispecific-antibodies-show-encouraging-anti

Novel Regeneron Bispecific Antibodies Show Encouraging ... Novel Regeneron bispecific antibodies show encouraging anti-tumor activity in two advanced solid tumors.

5. asco.org asco.org/videos-slides/VIDEOSANDSLIDES213302

A phase 1/2 study of REGN5093-M114, a METxMET ... A phase 1/2 study of REGN5093-M114, a METxMET antibody-drug conjugate, in patients with mesenchymal epithelial transition factor (MET)-overexpressing NSCLC.

6. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/1744/phase-12-study-regn5093-m114/

A PHASE 1/2 STUDY OF REGN5093-M114 (METXMET ... The purpose of the study is to determine and investigate the safety, tolerability and efficacy of REGN5093-M114, a METxMET ADC, in patients with ...