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

NCT04868877 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: MCLA-129-CL012024-514461-19-00
• Study Type: interventional
• Target: 194
• Locations: 9 countries
• Sites: 51

Brief Summary

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.

Conditions

Esophageal Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma; Colorectal Cancer; Gastric Cancer; Non-Small Cell Lung Cancer Metastatic

Keywords

MCLA-129; EGFR inhibitor; NSCLC; C-MET; GC/GEJ; Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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.

• To evaluate progression-free survival (PFS)

  From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.

• To evaluate overall survival (OS)

  From first dose until RECIST progression or until 1 year after treatment, whichever occurs first.

Study Arms (7)

Part 2 NSCLC Second-line or more harboring EGFR exon 20 Insertion

EXPERIMENTAL

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

Drug: MCLA-129

Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutation

EXPERIMENTAL

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

Drug: MCLA-129

Part 2 Selected solid tumors with or without an EGFR or cMet alteration

EXPERIMENTAL

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

Drug: MCLA-129

Part 2 NSCLC First-line harboring EGFR sensitizing mutations

EXPERIMENTAL

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; Drug: Osimertinib

Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib)

EXPERIMENTAL

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; Drug: Osimertinib

Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy)

EXPERIMENTAL

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; Drug: Chemotherapy

Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy)

EXPERIMENTAL

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; Drug: Chemotherapy

Interventions

MCLA-129 DRUG

full length IgG1 bispecific antibody that specifically targets the receptor tyrosine kinases EGFR and c-MET

Also known as: bispecific

Part 2 NSCLC First-line harboring EGFR sensitizing mutations; Part 2 NSCLC Second-line or more harboring EGFR exon 20 Insertion; Part 2 NSCLC Second-line or more harboring cMet exon 14 skipping mutation; Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy); Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib); Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy); Part 2 Selected solid tumors with or without an EGFR or cMet alteration

Osimertinib DRUG

Approved, 3rd-generation EGFR-TKI

Also known as: Tagrisso

Part 2 NSCLC First-line harboring EGFR sensitizing mutations; Part 2 NSCLC Second-line or more, osimertinib resistant (combo with osimertinib)

Chemotherapy DRUG

administrated by IV infusion

Part 2 NSCLC Second-line or more, osimertinib resistant (combo with chemotherapy); Part 2 NSCLC Third-line or more, osimertinib resistant, platinum resistant (combo with chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (51)

University of California, Irvine

Orange, California, 92868, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Next Oncology Virginia

Fairfax, Virginia, 22031, United States

Location

Institut Jules Bordet

Anderlecht, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Clinique de l'Europe

Amiens, 80090, France

Location

CHU Hopitaux de Bordeaux - Hôpital Saint-André

Bordeaux, 33000, France

Location

CHU de Lyon - Louis Pradel Hospital

Bron, 69677, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

Location

Hôpital Albert Calmette

Lille, 59037, France

Location

L'Institut Paoli - Calmettes

Marseille, 13009, France

Location

CHU de Nantes - Hôpital Nord Laennec

Nantes, 44093, France

Location

Marie Wislez

Paris, 75014, France

Location

Hôpital Bichat - Claude-Bernard

Paris, 75877, France

Location

Hôpital Européen Georges Pompidou (HEGP)

Paris, 75908, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

Hôpital d'Instruction des Armées Bégin

Saint-Mandé, 94163, France

Location

Krankenhaus Nordwest

Frankfurt am Main, Hesse, 60488, Germany

Location

Sana Klinikum Offenbach GmbH

Offenbach, 63069, Germany

Location

Istituto Nazionale dei Tumori Regina Elena

Roma, Rome, 00144, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 22162, Italy

Location

Azienda Ospedaliero - Universitaria San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona

Salerno, 84131, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento

Verona, 37126, Italy

Location

Netherlands Cancer Institute

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

National Cancer Centre of Singapore

Singapore, 169610, Singapore

Location

Gachon University Gil Hospital

Incheon, 21565, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital - Yonsei Cancer Center

Seoul, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Hospital HM Delfos

Barcelona, 08023, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

IOB Institute of Oncology - Hospital Quironsalud Barcelona

Barcelona, 8023, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Clínica Universidad de Navarra -Madrid

Madrid, 28027, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hospital Quirón Madrid

Madrid, 28223, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

Fundación Instituto Valenciano de Oncología (IVO)

Valencia, 46009, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Head and Neck Neoplasms

Interventions

osimertinib; Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: May 3, 2021
• Study Start: April 28, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2025-04

Locations

FR (12); SG (1); DE (2); IT (8); US (4); KR (6); NL (3); ES (13); BE (2)