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

Merus

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: MCLA-129; Drug: Osimertinib; Drug: Chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT04868877

MCLA-129-CL01

Details and patient eligibility

About

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.

Enrollment: 576 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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576 participants in 7 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: MCLA-129

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

Experimental group

Description:

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

Treatment:

Drug: MCLA-129

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

Experimental group

Description:

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

Treatment:

Drug: MCLA-129

Part 2 NSCLC First-line harboring EGFR sensitizing mutations

Experimental group

Description:

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:

Drug: Osimertinib

Drug: MCLA-129

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

Experimental group

Description:

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:

Drug: Osimertinib

Drug: MCLA-129

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

Experimental group

Description:

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.

Treatment:

Drug: Chemotherapy

Drug: MCLA-129

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

Experimental group

Description:

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.

Treatment:

Drug: Chemotherapy

Drug: MCLA-129