What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, chemotherapy, and immunotherapy. Targeted therapies, such as those involving bispecific antibodies like MCLA-129, work by specifically targeting molecular abnormalities in cancer cells. MCLA-129 targets both EGFR (Epidermal Growth Factor Receptor) and c-MET (a receptor tyrosine kinase), which are often overexpressed or mutated in NSCLC, leading to uncontrolled cell growth and survival. By inhibiting these pathways, MCLA-129 can effectively reduce tumor growth and proliferation. This is crucial for NSCLC patients as it offers a more personalized treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy. Chemotherapy, on the other hand, works by killing rapidly dividing cells but lacks specificity, often affecting healthy cells as well. Immunotherapy boosts the body's immune system to recognize and attack cancer cells, providing another avenue for treatment. Understanding these mechanisms helps in selecting the most appropriate therapy based on the patient's specific cancer profile.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) that target EGFR and c-MET, such as erlotinib and bevacizumab, have several known side effects. Erlotinib often causes rash, fatigue, and diarrhea. Bevacizumab, an anti-angiogenic agent, can lead to adverse events like hypertension, bleeding, and, in rare cases, intestinal perforation and arterial thrombosis. These side effects are important considerations when evaluating treatment options for NSCLC.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Small Cell Lung Cancer (NSCLC) that target the EGFR pathway, including gefitinib and erlotinib, which are tyrosine kinase inhibitors (TKIs) specifically targeting EGFR mutations. Additionally, therapies targeting the c-MET pathway, such as crizotinib, have been approved for NSCLC patients with specific genetic alterations. Immunotherapies like pembrolizumab and nivolumab, which target PD-1/PD-L1, have also been approved for NSCLC. While bispecific antibodies like MCLA-129 targeting both EGFR and c-MET are still under investigation, these existing therapies highlight the FDA's focus on targeted and immunotherapeutic approaches in NSCLC treatment.

What other types of research exist?

Promising alternatives to MCLA-129 for NSCLC patients include: 1) EGFR-TKIs such as osimertinib and rociletinib, which have shown significant activity against intracranial disease in EGFR-mutant NSCLC. 2) Bispecific antibodies targeting EGFR and Neuropilin-1, which have demonstrated potential in overcoming resistance in KRAS-mutant NSCLC. 3) Alectinib, an ALK inhibitor, which has shown efficacy in ALK+ NSCLC patients, including those refractory to prior treatments.

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Monoclonal Antibodies

MCLA-129 for Non-Small Cell Lung Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Merus N.V.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Patients with NSCLC, GC/GEJ, HNSCC, or ESCC who have failed prior standard first-line treatment. Patients must have progressed on or be intolerant to therapies that are known to provide clinical benefit. There is no limit to the number of prior treatment regimens

Must not have

Known history of HIV (HIV 1/2 antibodies)

Myocarditis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from first dose until recist progression or until 1 year after treatment, whichever occurs first.

Awards & highlights

Summary

This trial tests a new drug, MCLA-129, on its own in patients with advanced cancers who did not respond to previous treatments. The study will adjust doses to find the safest and most effective amount.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors like NSCLC, HNSCC, GC/GEJ, ESCC who've had no luck with standard treatments. They should be relatively healthy (ECOG 0-1), have a life expectancy of at least 12 weeks, and good organ function. People can't join if they've recently used other investigational drugs or therapies, had major surgery or certain cardiovascular issues.

What is being tested?

The study tests MCLA-129 alone in patients with various advanced cancers to find the maximum tolerated dose and/or recommended phase two dose. It's an early-phase trial that starts by giving small doses to a few people and increasing it for new groups until doctors find the best dose.

What are the potential side effects?

Possible side effects include typical reactions to cancer therapy such as fatigue, nausea, skin reactions at injection sites, allergic responses to proteins in the drug (like rashes), liver enzyme changes indicating stress on the liver, and potential impact on blood cell counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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My cancer has not responded to initial treatments.

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My cancer is advanced, cannot be surgically removed, and is considered incurable.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a known history of HIV.

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I have myocarditis.

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I have a serious fluid buildup around my heart.

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I haven't had major surgery or radiotherapy in the last 3 weeks.

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I have an active Hepatitis B infection and am not on antiviral treatment.

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I don't have untreated or symptomatic brain metastases needing immediate treatment.

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I do not have heart issues like long QT syndrome or a family history of it.

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My cancer has spread to the lining of my brain and spinal cord.

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I haven't had cancer treatment or immunotherapy in the last 4 weeks or less.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from first dose until recist progression or until 1 year after treatment, whichever occurs first.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from first dose until recist progression or until 1 year after treatment, whichever occurs first.

This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose until recist progression or until 1 year after treatment, whichever occurs first. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

To evaluate clinical activity, as assessed by ORR

Secondary study objectives

All safety endpoints

To evaluate overall survival (OS)

To evaluate preliminary antitumor activity in terms of BOR

+3 more

Trial Design

7Treatment groups

Experimental Treatment

Group I: Part 2 Selected solid tumors with or without an EGFR or cMet alterationExperimental Treatment1 Intervention

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).

Group II: Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy)Experimental Treatment2 Interventions

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance.

Group III: Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib)Experimental Treatment2 Interventions

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.

Group IV: Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy)Experimental Treatment2 Interventions

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and chemotherapy every three weeks per standard of care according to local guidance.

Group V: Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutationExperimental Treatment1 Intervention

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).

Group VI: Part 2 NSCLC Second-line or more harboring EGFR exon 20 InsertionExperimental Treatment1 Intervention

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).

Group VII: Part 2 NSCLC First-line harboring EGFR sensitizing mutationsExperimental Treatment2 Interventions

Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D) and Osimertinib orally once daily starting at a dose of 80mg.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Chemotherapy

2003

Completed Phase 4

~3050

Osimertinib

2017

Completed Phase 4

~1100

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, chemotherapy, and immunotherapy. Targeted therapies, such as those involving bispecific antibodies like MCLA-129, work by specifically targeting molecular abnormalities in cancer cells. MCLA-129 targets both EGFR (Epidermal Growth Factor Receptor) and c-MET (a receptor tyrosine kinase), which are often overexpressed or mutated in NSCLC, leading to uncontrolled cell growth and survival. By inhibiting these pathways, MCLA-129 can effectively reduce tumor growth and proliferation. This is crucial for NSCLC patients as it offers a more personalized treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy. Chemotherapy, on the other hand, works by killing rapidly dividing cells but lacks specificity, often affecting healthy cells as well. Immunotherapy boosts the body's immune system to recognize and attack cancer cells, providing another avenue for treatment. Understanding these mechanisms helps in selecting the most appropriate therapy based on the patient's specific cancer profile.

New targeted treatments in lung cancer--overview of clinical trials.