Trial Title:
Study Evaluating Zenocutuzumab in Patients with or Without Molecularly Defined Cancers
NCT ID:
NCT05588609
Condition:
NSCLC Harboring NRG1 Fusion
Metastatic Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Abiraterone Acetate
Afatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Parallel assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Afatinib Oral Tablet
Description:
anti epidermal growth factor receptor (EGFR)/HER2 agent
Arm group label:
Part 1: NSCLC harboring NRG1+ fusion
Arm group label:
Part 2: NSCLC harboring NRG1+ fusion
Other name:
GILOTRIF®
Other name:
GIOTRIF®
Intervention type:
Drug
Intervention name:
Enzalutamide Pill
Description:
second-generation androgen receptor antagonist
Arm group label:
Part 1: mCRPC
Arm group label:
Part 2: mCRPC
Other name:
XTANDI®
Intervention type:
Drug
Intervention name:
Abiraterone acetate tablets
Description:
androgen synthesis inhibitor
Arm group label:
Part 1: mCRPC
Arm group label:
Part 2: mCRPC
Other name:
ZYTIGA®
Intervention type:
Biological
Intervention name:
MCLA-128
Description:
full length IgG1 bispecific antibody targeting HER2 and HER3
Arm group label:
Part 1: NSCLC harboring NRG1+ fusion
Arm group label:
Part 1: mCRPC
Arm group label:
Part 2: NSCLC harboring NRG1+ fusion
Arm group label:
Part 2: mCRPC
Other name:
Zenocutuzumab
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Oncology Institute of Hope & Innovation
Address:
City:
Whittier
Zip:
90603
Country:
United States
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Lake Mary
Zip:
32746
Country:
United States
Facility:
Name:
The Center for Cancer and Blood Disorders
Address:
City:
Bethesda
Zip:
20817
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
TriHealth Cancer Institute
Address:
City:
Cincinnati
Zip:
45220
Country:
United States
Facility:
Name:
University Hospitals - Seidman Cancer Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Facility:
Name:
Northwest Medical Specialties
Address:
City:
Tacoma
Zip:
98405
Country:
United States
Start date:
November 17, 2022
Completion date:
March 2026
Lead sponsor:
Agency:
Merus N.V.
Agency class:
Industry
Source:
Merus N.V.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05588609
