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Trial record 4 of 4 for:    MCLA-128

Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers

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ClinicalTrials.gov Identifier: NCT05588609
Recruitment Status : Recruiting
First Posted : October 20, 2022
Last Update Posted : December 22, 2022
Sponsor:
Information provided by (Responsible Party):
Merus N.V.

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


Condition or disease Intervention/treatment Phase
NSCLC Harboring NRG1 Fusion Metastatic Castration-resistant Prostate Cancer Drug: Afatinib Oral Tablet Drug: Enzalutamide Pill Drug: Abiraterone acetate tablets Biological: MCLA-128 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study Evaluating Activity of Zenocutuzumab (MCLA-128) in Patients With or Without Molecularly Defined Cancers
Actual Study Start Date : November 17, 2022
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Afatinib Oral Tablet
anti epidermal growth factor receptor (EGFR)/HER2 agent
Other Names:
  • GILOTRIF®
  • GIOTRIF®

Biological: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: Zenocutuzumab

Experimental: 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.

Drug: Enzalutamide Pill
second-generation androgen receptor antagonist
Other Name: XTANDI®

Drug: Abiraterone acetate tablets
androgen synthesis inhibitor
Other Name: ZYTIGA®

Biological: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: Zenocutuzumab

Experimental: 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.
Drug: Afatinib Oral Tablet
anti epidermal growth factor receptor (EGFR)/HER2 agent
Other Names:
  • GILOTRIF®
  • GIOTRIF®

Biological: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: Zenocutuzumab

Experimental: 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

Drug: Enzalutamide Pill
second-generation androgen receptor antagonist
Other Name: XTANDI®

Drug: Abiraterone acetate tablets
androgen synthesis inhibitor
Other Name: ZYTIGA®

Biological: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: Zenocutuzumab




Primary Outcome Measures :
  1. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of response. [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Objective Response Rate (ORR) by local assessment per RECIST v1.1

  2. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of Prostate-Specific antigen level ≥ 50% (PSA50) response. [ Time Frame: Every 4 weeks until study ends, approximately 2 years ]
    PSA50 response rate


Secondary Outcome Measures :
  1. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Objective Response Rate (ORR) per RECIST v1.1

  2. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Duration of Response (DOR) per RECIST v1.1

  3. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Time to Response (TTR) per RECIST v1.1

  4. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Objective Response Rate (ORR) per RECIST v1.1

  5. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Duration of Response (DOR) per RECIST v1.1

  6. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Time to Response (TTR) per RECIST v1.1

  7. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by independent central review [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Progression-free Survival (PFS) per RECIST v1.1

  8. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of antitumor activity as assessed by local investigator [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Progression-free Survival (PFS) per RECIST v1.1

  9. Group A: Evaluate efficacy of zenocutuzumab in combination with afatinib in terms of survival [ Time Frame: Continuous through study completion, up to 2 years ]
    Overall Survival (OS)

  10. Group A: Evaluate safety and tolerability of zenocutuzumab in combination with afatinib [ Time Frame: continuous through study completion, an average of 9 months ]
    Frequency and nature of adverse events (AEs) that are related to treatment as assessed by Common Terminology Criteria for AEs (CTCAE) version 5.0

  11. Group A: Maximum plasma concentration [Cmax] of zenocutuzumab when given in combination with afatinib [ Time Frame: 12 months ]
    Cmax

  12. Group A: Characterize immunogenicity of zenocutuzumab. [ Time Frame: 12 months ]
    Incidence of antidrug antibodies against zenocutuzumab

  13. Group A: Area under the concentration versus time curve from time zero to time t [AUC0-t] of zenocutuzumab when given in combination with afatinib [ Time Frame: 12 months ]
    AUC0-t

  14. Group A: Area under the concentration versus time curve [AUC0-∞] of zenocutuzumab when given in combination with afatinib [ Time Frame: 12 months ]
    AUC0-∞

  15. Group A: Area under the concentration versus time curve [AUC0-∞] of afatinib when given in combination with zenocutuzumab [ Time Frame: 12 months ]
    AUC0-∞

  16. Group A: Area under the concentration versus time curve from time zero to time t [AUC0-t] afatinib when given in combination with zenocutuzumab [ Time Frame: 12 months ]
    AUC0-t

  17. Group A: Maximum plasma concentration [Cmax] afatinib when given in combination with zenocutuzumab [ Time Frame: 12 months ]
    Cmax

  18. Group A: Characterize immunogenicity of zenocutuzumab. [ Time Frame: 12 months ]
    Serum titers of antidrug antibodies against zenocutuzumab

  19. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of antitumor activity as assessed by local investigator. [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Objective Response Rate (ORR) per RECIST v1.1

  20. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of Prostate-specific antigen level ≥ 30% (PSA30) response. [ Time Frame: Every 4 weeks until study ends, approximately 2 years ]
    PSA30 response rate

  21. Group B: Evaluate efficacy zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of survival parameters [ Time Frame: Continuous through study completion, up to 2 years ]
    Radiographic Progression Free Survival (rPFS) by local investigator per Prostate Cancer Clinical Trials Working Group 3 Modified Response Evaluation Criteria in Solid Tumors (PCWG3-modified RECIST) v1.1 and Overall Survival (OS)

  22. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of antitumor activity as assessed by local investigator. [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Duration of Response (DOR) per PCWG3-modified RECIST v1.1

  23. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of antitumor activity as assessed by local investigator. [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    Time to Response (TTR) per PCWG3-modified RECIST v1.1

  24. Group B: Evaluate efficacy of zenocutuzumab in combination with enzalutamide or abiraterone acetate in terms of Prostate-specific antigen level ≥ 30% (PSA30) response. [ Time Frame: Every 8 weeks until study ends, approximately 2 years ]
    time to Prostate-specific antigen (PSA) progression per PCWG3-modified RECIST v1.1

  25. Group B: Evaluate safety and tolerability of zenocutuzumab in combination with enzalutamide or abiraterone acetate. [ Time Frame: continuous through study completion, an average of 6 months ]
    Frequency and nature of adverse events (AEs) that are related to treatment as assessed by Common Terminology Criteria for AEs (CTCAE) version 5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: (Groups A, B)

  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.

Inclusion Criteria: (Group A Only)

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.

Inclusion Criteria: (Group B Only) B1. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features. B2. Metastatic disease documented by at least 2 bone lesions on whole body bone scintigraphy, or soft tissue disease documented by computed tomography (CT) scan/magnetic resonance imaging (MRI). B3. Ongoing androgen deprivation with a serum testosterone level ≤ 1.73 nmol/L (≤ 50 ng/dL) at Screening. B4. Current ongoing therapy with a next-generation AR signaling inhibitor (enzalutamide or abiraterone) started at least 90 days before Screening. B5. Progressive disease by PCWG3 criteria B6. Able to swallow oral medications and absence of gastrointestinal conditions (eg, malabsorption, resection) deemed to jeopardize intestinal absorption.

Exclusion Criteria: (Groups A, B)

  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.

Exclusion Criteria: (Group A) A1. Patients previously exposed to afatinib. A2. History of interstitial lung disease (ILD), ILD-like adverse reactions (such as lung infiltration, pneumonitis, acute respiratory distress syndrome, allergic alveolitis), or radiation pneumonia requiring steroid therapy.

Exclusion Criteria: (Group B) B1. More than 2 lines of a second-generation hormonal agent for metastatic disease.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05588609


Contacts
Layout table for location contacts
Contact: Shekeab Jauhari, MD 617-401-4499 USenquiries@merus.nl

Locations
Layout table for location information
United States, California
The Oncology Institute of Hope & Innovation Recruiting
Whittier, California, United States, 90603
Contact: Mary Rodriguez         
Principal Investigator: Paul La Porte, MD         
United States, Florida
Florida Cancer Specialists Recruiting
Lake Mary, Florida, United States, 32746
Contact: Jessica Keville    407-804-6133    jessica.keville@flcancer.com   
Principal Investigator: Alexander Philipovskiy, MD, PhD         
Sponsors and Collaborators
Merus N.V.
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Responsible Party: Merus N.V.
ClinicalTrials.gov Identifier: NCT05588609    
Other Study ID Numbers: MCLA-128-CL03
First Posted: October 20, 2022    Key Record Dates
Last Update Posted: December 22, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Abiraterone Acetate
Afatinib
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors
Protein Kinase Inhibitors