REGN5093-M114 for Non-Small Cell Lung Cancer

Recruiting at 20 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug alone and in combination with another treatment in patients with advanced lung cancer that has high levels of a specific protein. The goal is to see if the drug is safe and effective in stopping cancer growth and helping the immune system fight the cancer.

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.

What data supports the idea that REGN5093-M114 for Non-Small Cell Lung Cancer is an effective treatment?

The available research shows that REGN5093-M114, a drug targeting MET, is effective in treating non-small cell lung cancer (NSCLC) with MET genetic changes. It has shown significant and lasting tumor reduction in models with high MET levels, even when other treatments fail. This suggests it could be a promising option for patients whose cancer does not respond to current MET-targeted therapies. ^{1 2 3 4 5}

What data supports the effectiveness of the drug REGN5093-M114 for treating non-small cell lung cancer?

Research shows that REGN5093-M114, a drug designed to target MET, can effectively treat lung cancers with high MET expression, even those resistant to other MET-targeted therapies. In preclinical studies, it led to significant tumor reduction in models with moderate to high MET levels, suggesting it could be a promising option for certain lung cancer patients. ^{1 2 3 4 5}

What safety data is available for REGN5093-M114 in treating non-small cell lung cancer?

The preclinical study of REGN5093-M114, a METxMET antibody-drug conjugate, showed that it was well tolerated in a cynomolgus monkey toxicology study at doses providing sufficient circulating drug concentrations for maximal antitumor activity in mouse models. This suggests a promising safety profile for further clinical evaluation. ^{1 2 3 4 6}

Is REGN5093-M114 safe for humans?

In a study with monkeys, REGN5093-M114 was well tolerated at doses that were effective in reducing tumors in mice, suggesting it may be safe for humans, but more research is needed to confirm this. ^{1 2 3 4 6}

Is the drug REGN5093-M114 a promising treatment for Non-Small Cell Lung Cancer?

Yes, REGN5093-M114 is a promising drug for Non-Small Cell Lung Cancer because it targets a specific protein called MET, which is often involved in cancer growth. It has shown the ability to shrink tumors in cases where other treatments have failed, especially in lung cancers with high MET levels. This makes it a potential new option for many patients. ^{1 2 3 7 8}

What makes the drug REGN5093-M114 unique for treating non-small cell lung cancer?

REGN5093-M114 is unique because it is an antibody-drug conjugate (ADC) that targets MET, a protein often involved in resistance to other treatments, and it can effectively treat tumors that do not respond to existing MET-targeted therapies. This drug combines a MET-targeting antibody with a cytotoxic agent, allowing it to overcome resistance and promote tumor regression in MET-overexpressing cancers. ^{1 2 3 7 8}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. United States 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. [2023]

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

A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade. [2023]

3. United States 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). [2022]

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

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

Antibody drug conjugates in non-small cell lung cancer: An emerging therapeutic approach. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

In vivo safety testing of Antibody Drug Conjugates. [2021]

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

Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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