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

Phase 1/2 Dose Escalation and Expansion Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors

A phase 1/2 open-label multicenter study will be performed with an initial dose escalation part to determine the MTD and/or the RP2D of MCLA-129 in monotherapy or in combination in patients with NSCLC, HNSCC, GC/GEJ, ESCC, or other solid tumors and who are treatment naïve or have progressed after receiving prior therapy for advanced/metastatic disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Non-Small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: MCLA-129; Drug: Osimertinib; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
• France
  • Amiens, France, 80090
    • Clinique de l'Europe
  • Bordeaux, France, 33000
    • CHU Hopitaux de Bordeaux - Hôpital Saint-André
  • Bron, France, 69677
    • CHU de Lyon - Louis Pradel Hospital
  • Créteil, France, 94010
    • Centre Hospitalier Intercommunal de Créteil
  • Lille, France, 59037
    • Hôpital Albert Calmette
  • Marseille, France, 13009
    • L'Institut Paoli - Calmettes
  • Nantes, France, 44093
    • CHU de Nantes - Hopital Nord Laennec
  • Paris, France, 75877
    • Hôpital Bichat - Claude-Bernard
  • Paris, France, 75014
    • Marie Wislez
  • Paris, France, 75908
    • Hôpital Européen Georges Pompidou (HEGP)
  • Poitiers, France, 86000
    • CHU de Poitiers
  • Saint-Mandé, France, 94163
    • Hôpital d'Instruction des Armées BEGIN
• Germany
  • Offenbach, Germany, 63069
    • Sana Klinikum Offenbach GmbH
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Krankenhaus Nordwest
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 22162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
  • Salerno, Italy, 84131
    • Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento
  • Rome
    • Roma, Rome, Italy, 00144
      • Istituto Nazionale dei Tumori Regina Elena
• Netherlands
  • Amsterdam, Netherlands
    • Netherlands Cancer Institute
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre of Singapore
• South Korea
  • Incheon, South Korea, 21565
    • Gachon University Gil Hospital
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea, 6351
    • Samsung Medical Center
  • Seoul, South Korea
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea
    • Severance Hospital - Yonsei Cancer Center
  • Suwon, Gyeonggi-do, South Korea, 16247
    • The Catholic University of Korea, St. Vincent's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08023
    • Hospital HM Delfos
  • Barcelona, Spain, 8023
    • IOB Institute of Oncology - Hospital Quironsalud Barcelona
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jimenez Díaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28223
    • Hospital Quiron Madrid
  • Madrid, Spain, 28027
    • Clínica Universidad de Navarra -Madrid
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Valencia, Spain, 46009
    • Fundacion Instituto Valenciano de Oncologia (IVO)
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Next Oncology Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 NSCLC, HNSCC, other solid tumors and applicable mutations as determined by the investigator.

• Availability of archival or a fresh tumor tissue sample.
• Measurable disease as defined by RECIST version 1.1 by radiologic methods.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks, as per Investigator.
• Adequate organ function (as per protocol)

Exclusion Criteria:

• Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy (> 10 mg prednisone or equivalent) to control symptoms within 14 days of study entry.
• Known leptomeningeal involvement.
• Participation in another clinical study or treatment with any investigational drug within 4 weeks prior to study entry.
• Systemic anticancer therapy or immunotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of study drug. For cytotoxic agents that have major delayed toxicity (e.g., mitomycin C, nitrosoureas), a washout period of 6 weeks is required.
• Major surgery or radiotherapy within 3 weeks of the first dose of study drug. Patients who received prior radiotherapy to ≥25% of bone marrow at any time are not eligible.
• Persistent grade >1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 NCI-CTCAE v5.0 and hypothyroidism ≤ grade 2 which is stable on hormone replacement are allowed.
• History of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents. History of hypersensitivity reaction or any toxicity attributed to chemotherapy and components.
• History of clinically significant cardiovascular disease
• Past medical history of ILD or pneumonitis, or any evidence of clinically active ILD or pneumonitis.
• Previous or concurrent malignancy, excluding non-basal cell carcinomas of skin or carcinoma in situ of the uterine cervix, unless the tumor was treated with curative or palliative intent and in the opinion of the Investigator, with Sponsor agreement, the previous or concurrent malignancy condition does not affect the assessment of safety and efficacy of the study drug.
• Current serious illness or medical conditions including, but not limited to uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
• Active Hepatitis B infection without receiving antiviral treatment.
• Positive test for Hepatitis C
• Known history of HIV (HIV 1/2 antibodies). Patients with HIV with undetectable viral load are allowed. In

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 2 NSCLC Second-line or more harboring EGFR exon 20 Insertion; Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific
Experimental: Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutation; Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific
Experimental: Part 2 Selected solid tumors with or without an EGFR or cMet alteration; Participants will receive intravenous infusion of MCLA-129 every two weeks at the recommended Phase II dose (RP2D).	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific
Experimental: Part 2 NSCLC First-line harboring EGFR sensitizing mutations; 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.	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific; Drug: Osimertinib; Approved, 3rd-generation EGFR-TKI; Other Names: Tagrisso
Experimental: Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib); 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.	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific; Drug: Osimertinib; Approved, 3rd-generation EGFR-TKI; Other Names: Tagrisso
Experimental: Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy); 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.	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific; Drug: Chemotherapy; administrated by IV infusion
Experimental: Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy); 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.	Drug: MCLA-129; full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET; Other Names: bispecific; Drug: Chemotherapy; administrated by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)	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.	First 28 days of treatment
To evaluate clinical activity, as assessed by ORR	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.	From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate preliminary antitumor activity in terms of BOR	To evaluate preliminary antitumor activity of MCLA-129 monotherapy as well as in combination with an EGFR TKI or chemotherapy in terms of best overall response (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	To evaluate preliminary antitumor activity of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Disease Control Rate (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	To evaluate preliminary antitumor activity of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy in terms of Duration of Response (DoR)	From first dose until RECIST progression or initiation of an alternative treatment, whichever occurs first.
To evaluate progression-free survival (PFS)	To evaluate progression-free survival (PFS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.	From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.
To evaluate overall survival (OS)	To evaluate overall survival (OS) of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.	From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy		From first dose until study treatment discontinuation
Proportion of patient with treatment discontinuations of single-agent MCLA-129 as well as in combination with an EGFR TKI or with chemotherapy.		From first dose until study treatment discontinuation
AE, regardless of relationship to study treatment		From first dose until study treatment discontinuation
All safety endpoints	including vital sign, lab, ECG, ECHO, 4 weeks CT scan, Eye exam	From first dose until study treatment discontinuation

Collaborators and Investigators

• Sponsor: Merus B.V.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; NSCLC; EGFR inhibitor; MCLA-129; C-MET; GC/GEJ
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Stomach Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms; Therapeutics; Drug Therapy; osimertinib
• Other Study ID Numbers: MCLA-129-CL01; 2024-514461-19-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No