Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers

NCT ID: NCT05588609

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-17
• Study Completion Date: 2025-07-03

Brief Summary

This is a Phase II, open-label, 2-arm, multicenter, international study designed to evaluate the efficacy of zenocutuzumab alone or in combination in patients with the following diagnoses:

Group A: NRG1+ NSCLC Group B: mCRPC

Detailed Description

Study Design:

This is an open label (all participants know the identity of the study drug), multicenter (more than one study site), study consisting of 2 parts:

Group A (NRG1+ NSCLC): Approximately 50 NRG1+NSCLC patients will be enrolled and will receive zenocutuzumab in combination with afatinib 40 mg orally once daily.

Group B (mCRPC): Up to 40 mCRPC patients will be enrolled and will receive zenocutuzumab in combination with the AR targeting agent enzalutamide or abiraterone on which they experienced disease progression immediately before study entry.

For the administration of zenocutuzumab in combination in Groups A and B, the Treatment Period will include 2 phases, an initial safety run-in phase, and an expansion phase with an interim efficacy analysis.

The study will consist of 4 periods: Screening, Treatment, Safety Follow-up, and Long-term Follow up.

Conditions

NSCLC Harboring NRG1 Fusion; Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: NSCLC harboring NRG1+ fusion

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with afatinib 40 mg orally once daily.

Group Type: EXPERIMENTAL

MCLA-128

Intervention Type: BIOLOGICAL

full length IgG1 bispecific antibody targeting HER2 and HER3

Afatinib Oral Tablet

Intervention Type: DRUG

anti epidermal growth factor receptor (EGFR)/HER2 agent

Part 1: mCRPC

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with the AR targeting agent they experienced disease progression on prior to study entry:

enzalutamide 160 mg orally once daily or abiraterone 1000 mg orally once daily with prednisone 5 mg orally twice daily.

Group Type: EXPERIMENTAL

Enzalutamide Pill

Intervention Type: DRUG

second-generation androgen receptor antagonist

Abiraterone acetate tablets

Intervention Type: DRUG

androgen synthesis inhibitor

MCLA-128

Intervention Type: BIOLOGICAL

full length IgG1 bispecific antibody targeting HER2 and HER3

Part 2: NSCLC harboring NRG1+ fusion

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with afatinib 40 mg orally once daily.

Group Type: EXPERIMENTAL

MCLA-128

Intervention Type: BIOLOGICAL

full length IgG1 bispecific antibody targeting HER2 and HER3

Afatinib Oral Tablet

Intervention Type: DRUG

anti epidermal growth factor receptor (EGFR)/HER2 agent

Part 2: mCRPC

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with the AR targeting agent they experienced disease progression on prior to study entry:

enzalutamide 160 mg orally once daily or abiraterone 1000 mg orally once daily with prednisone 5 mg orally twice daily

Group Type: EXPERIMENTAL

Enzalutamide Pill

Intervention Type: DRUG

second-generation androgen receptor antagonist

Abiraterone acetate tablets

Intervention Type: DRUG

androgen synthesis inhibitor

MCLA-128

Intervention Type: BIOLOGICAL

full length IgG1 bispecific antibody targeting HER2 and HER3

Interventions

Enzalutamide Pill

second-generation androgen receptor antagonist

Intervention Type: DRUG

Abiraterone acetate tablets

androgen synthesis inhibitor

Intervention Type: DRUG

MCLA-128

full length IgG1 bispecific antibody targeting HER2 and HER3

Intervention Type: BIOLOGICAL

Afatinib Oral Tablet

anti epidermal growth factor receptor (EGFR)/HER2 agent

Intervention Type: DRUG

Other Intervention Names

GILOTRIF®; GIOTRIF®; XTANDI®; ZYTIGA®; Zenocutuzumab

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent before initiation of any study procedures.

2. Age ≥ 18 years at signature of informed consent.

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

4. Estimated life expectancy of ≥ 12 weeks.

5. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA).

6. Adequate organ function:

• Absolute neutrophil count ≥ 1.5 × 109/L.
• Hemoglobin ≥ 9 g/dL.
• Platelets ≥ 100 × 109/L.
• Serum calcium within normal ranges (or corrected with supplements).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (in case of liver involvement by malignancy, ALT/AST ≤ 5 × ULN will be allowed).
• Total bilirubin ≤ 1.5 × ULN (in case of Gilbert disease, total bilirubin ≤ 3 × ULN will be allowed).
• Estimated glomerular filtration rate of > 30 mL/min based on the Cockroft-Gault formula (Appendix D).
• Serum albumin > 3.0 g/dL.

7. Availability of a representative tumor specimen, either a formalin-fixed paraffin embedded (FFPE) de novo (ie, obtained up to 2 months before signing of the informed consent form [ICF]) or an FFPE archival tumor sample, preferably collected within 2 years of the start of study treatment. A fresh FFPE sample is preferred.

8. Sexually active male and female patients of childbearing potential must agree to use contraceptive measures.

A1. Have histologically confirmed locally advanced, unresectable, or metastatic NSCLC harboring an NRG1 gene fusion detected by DNA- or RNA-based next generation sequencing in a tumor sample or in plasma-cell free DNA. A2. Have received prior standard therapy appropriate for the tumor type and disease or must be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy in the opinion of the Investigator or have no satisfactory available treatment options. A3. Have at least 1 measurable lesion per RECIST v1.1. A4. Able to swallow oral medications and absence of gastrointestinal conditions (eg, malabsorption, resection) deemed to jeopardize intestinal absorption.

Exclusion Criteria

1. Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.

2. Previous exposure to anti-HER3-directed therapies.

3. Known leptomeningeal involvement.

4. Participation in another interventional clinical trial or treatment with any investigational drug within 4 weeks before study entry.

5. Chronic use of high-dose oral corticosteroid therapy (> 10 mg of prednisone- equivalent a day).

6. Uncontrolled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) or unstable angina.

7. History of congestive heart failure Class II-IV by New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, or paroxysmal supraventricular tachycardia).

8. History of myocardial infarction within 6 months of study entry.

9. History of prior or concomitant malignancies (other than excised nonmelanoma skin cancer, cured in situ cervical carcinoma, or low-grade Ta or T1 urothelial carcinoma of the bladder that has undergone potentially curative therapy) within 3 years of study entry.

10. Current serious illness or medical conditions including, but not limited to uncontrolled active infection, and clinically significant pulmonary, metabolic, or psychiatric disorders.

11. Patients with the following known infectious diseases:

• Known active hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) without receiving antiviral treatment.
• Known positive test for hepatitis C virus (HCV) RNA.

12. Known human immunodeficiency virus (HIV)-positive patients unless the CD4+ count is ≥ 300/μL, viral load is undetectable, and the patient is currently receiving highly active antiretroviral therapy.

B2. More than 2 lines of systemic chemotherapy for metastatic disease. B3. Patients with only nonmeasurable lesions other than bone metastasis (eg, pleural effusion, ascites, other visceral locations). B4. A history of seizure or any condition predisposing patient to seizure within 12 months before study treatment, including history of unexplained loss of consciousness or transient ischemic attack, for patients receiving enzalutamide.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merus N.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Oncology Institute of Hope & Innovation

Whittier, California, United States

Florida Cancer Specialists

Lake Mary, Florida, United States

The Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

TriHealth Cancer Institute

Cincinnati, Ohio, United States

University Hospitals - Seidman Cancer Center

Cleveland, Ohio, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Countries

United States

Other Identifiers

MCLA-128-CL03

Identifier Type: -

Identifier Source: org_study_id