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MCLA-129

Phase 1

Non-Small Cell Lung Cancer Metastatic | Small molecule | Oncology |Merus N.V.|Last Updated: Feb 19, 2026

Target and mechanism

Molecular targetEGFR, c-MET
Target classReceptor
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment194

FDA Designations

No designations recorded

Clinical trial landscape

MCLA-129 · 1 trial · 5 indications

Phase 1 1
NCT04868877Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in CombinationNon-Small Cell Lung Cancer Metastatic
ACTIVE NOT_RECRUITING194 Analytics
PHASE1ACTIVE NOT_RECRUITING
Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in Combination
Non-Small Cell Lung Cancer MetastaticUnlock trial analytics

Study Endpoints

Primary Endpoints

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
First 28 days of treatment

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single-agent MCLA-129 as well as in combination with chemotherapy in patients with NSCLC, GC/GEJ adenocarcinoma, HNSCC or ESCC, with disease progression after prior therapy for advanced/metastatic disease.

To evaluate clinical activity, as assessed by ORR
From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.

To evaluate the ORR of MCLA-129 monotherapy or in combination with an EGFR TKI or chemotherapy in molecularly defined populations of advanced/metastatic solid tumors.

Secondary Endpoints

To evaluate preliminary antitumor activity in terms of BOR
From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
To evaluate preliminary antitumor activity in terms of DCR
From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
To evaluate preliminary antitumor activity in terms of DoR
From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Part 2 NSCLC Second-line or more harboring EGFR exon 20 InsertionEXPERIMENTALParticipants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutationEXPERIMENTALParticipants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
Part 2 Selected solid tumors with or without an EGFR or cMet alterationEXPERIMENTALParticipants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).
Part 2 NSCLC First-line harboring EGFR sensitizing mutationsEXPERIMENTALParticipants 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.
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib)EXPERIMENTALParticipants 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.
Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy)EXPERIMENTALParticipants 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.
Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy)EXPERIMENTALParticipants 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.

Interventions

NameTypeDescription
MCLA-129DRUGfull length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET
OsimertinibDRUGApproved, 3rd-generation EGFR-TKI
ChemotherapyDRUGadministrated by IV infusion
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites51

Part One: 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. Part Two: Patients with ...

Countries:United StatesBelgiumFranceGermanyItalyNetherlandsSingaporeSouth KoreaSpain
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Competitive Landscape -Non-Small Cell Lung Cancer 389 trials (matched to "Non-Small Cell Lung Cancer Metastatic")

Frequently asked questions about MCLA-129

What is MCLA-129 used for in Non-Small Cell Lung Cancer Metastatic?

MCLA-129 is an investigational bispecific antibody being studied for the treatment of metastatic non-small cell lung cancer. It is also being evaluated in other solid tumors including gastric cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and colorectal cancer. The drug is currently in Phase 1 clinical development.

What does MCLA-129 target?

MCLA-129 targets EGFR and c-MET, two receptor proteins involved in tumor growth. As a bispecific antibody, it is designed to bind to both targets simultaneously. This dual targeting approach is being investigated in advanced solid tumors, particularly metastatic non-small cell lung cancer.

Who makes MCLA-129?

MCLA-129 is being developed by Merus N.V., a biopharmaceutical company. Merus is listed on the stock exchange under the ticker symbol MRUS. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational drug in patients with advanced solid tumors.

What phase is MCLA-129 in?

MCLA-129 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The ongoing Phase 1/2 study is currently active but not recruiting participants, and is evaluating the drug alone and in combination for advanced solid tumors.

What clinical trials is MCLA-129 in?

MCLA-129 is being studied in clinical trial NCT04868877, a Phase 1/2 study evaluating the drug alone and in combination in advanced NSCLC and other solid tumors. The trial has enrolled 194 participants across multiple countries including the United States, Belgium, France, Germany, Italy, Netherlands, Singapore, South Korea, and Spain.

Is MCLA-129 the same as a bispecific antibody?

Yes, MCLA-129 is a bispecific antibody designed to target both EGFR and c-MET. It is being developed by Merus N.V. for the treatment of advanced solid tumors. The drug is currently in Phase 1 clinical trials and has not yet been approved for commercial use.