Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers

NCT05588609 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: MCLA-128-CL03
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 7

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

Conditions

NSCLC Harboring NRG1 Fusion; Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of response.

  Objective Response Rate (ORR) by local assessment per RECIST v1.1

  Every 8 weeks until study ends, approximately 2 years

• Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of Prostate-Specific antigen level ≥ 50% (PSA50) response.

  PSA50 response rate

  Every 4 weeks until study ends, approximately 2 years

Secondary Outcomes (25)

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator

  Every 8 weeks until study ends, approximately 2 years

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator

  Every 8 weeks until study ends, approximately 2 years

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator

  Every 8 weeks until study ends, approximately 2 years

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review

  Every 8 weeks until study ends, approximately 2 years

• Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review

  Every 8 weeks until study ends, approximately 2 years

Study Arms (4)

Part 1: NSCLC harboring NRG1+ fusion

EXPERIMENTAL

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

Drug: Afatinib Oral Tablet; Biological: MCLA-128

Part 1: mCRPC

EXPERIMENTAL

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.

Drug: Enzalutamide Pill; Drug: Abiraterone acetate tablets; Biological: MCLA-128

Part 2: NSCLC harboring NRG1+ fusion

EXPERIMENTAL

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

Drug: Afatinib Oral Tablet; Biological: MCLA-128

Part 2: mCRPC

EXPERIMENTAL

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

Drug: Enzalutamide Pill; Drug: Abiraterone acetate tablets; Biological: MCLA-128

Interventions

Afatinib Oral Tablet DRUG

anti epidermal growth factor receptor (EGFR)/HER2 agent

Also known as: GILOTRIF®, GIOTRIF®

Part 1: NSCLC harboring NRG1+ fusion; Part 2: NSCLC harboring NRG1+ fusion

Enzalutamide Pill DRUG

second-generation androgen receptor antagonist

Also known as: XTANDI®

Part 1: mCRPC; Part 2: mCRPC

Abiraterone acetate tablets DRUG

androgen synthesis inhibitor

Also known as: ZYTIGA®

Part 1: mCRPC; Part 2: mCRPC

MCLA-128 BIOLOGICAL

full length IgG1 bispecific antibody targeting HER2 and HER3

Also known as: Zenocutuzumab

Part 1: NSCLC harboring NRG1+ fusion; Part 1: mCRPC; Part 2: NSCLC harboring NRG1+ fusion; Part 2: mCRPC

Eligibility Criteria

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

You may qualify if:

• Signed informed consent before initiation of any study procedures.
• Age ≥ 18 years at signature of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Estimated life expectancy of ≥ 12 weeks.
• Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA).
• 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.
• 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.

You may not qualify if:

• 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.
• Previous exposure to anti-HER3-directed therapies.
• Known leptomeningeal involvement.
• Participation in another interventional clinical trial or treatment with any investigational drug within 4 weeks before study entry.
• Chronic use of high-dose oral corticosteroid therapy (\> 10 mg of prednisone- equivalent a day).
• Uncontrolled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) or unstable angina.
• 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).
• History of myocardial infarction within 6 months of study entry.
• 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.
• Current serious illness or medical conditions including, but not limited to uncontrolled active infection, and clinically significant pulmonary, metabolic, or psychiatric disorders.
• 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.
• 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.

Sponsors & Collaborators

• Partner Therapeutics, Inc.: lead

Study Sites (7)

The Oncology Institute of Hope & Innovation

Whittier, California, 90603, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

The Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

TriHealth Cancer Institute

Cincinnati, Ohio, 45220, United States

Location

University Hospitals - Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Interventions

Afatinib; enzalutamide; Abiraterone Acetate; zenocutuzumab

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel assignment

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 20, 2022
• Study Start: November 17, 2022
• Primary Completion: July 3, 2025
• Study Completion: July 3, 2025
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)