Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors

Phase 2

Terminated

Conditions: Sarcoma
Bladder Cancer
Gallbladder Cancer
Bile Duct Cancer
Pancreatic Cancer
Lung Cancer
Colorectal Cancer
Ovarian Cancer
Locally Advanced Solid Tumor
Breast Cancer

Interventions: Drug: Seribantumab

Registration Number: NCT04383210

Lead Sponsor: Elevation Oncology

Brief Summary: This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 75

Inclusion Criteria

To be eligible for participation in the study, patients must meet the following inclusion criteria:

Locally-advanced or metastatic solid tumor with an NRG1 gene fusion identified through molecular assays, such as PCR, NGS (RNA or DNA) or FISH, by a CLIA-certified or similarly accredited laboratory
Availability of fresh or archived FFPE tumor sample to be submitted to a central laboratory for confirmation of NRG1 gene fusion status
Patients should have received a minimum of one prior standard therapy appropriate for their tumor type and stage of disease, progressed or been nonresponsive to these available therapies, with no further available curative therapy options
≥ 18 years of age
ECOG performance status (PS) 0, 1 or 2
Patients must have at least one measurable extra-cranial lesion as defined by RECIST v1.1
Adequate hepatic function defined as:
Serum AST and serum ALT < 2.5 × upper limit of normal (ULN), or AST and ALT < 5 × ULN if liver function abnormalities due to underlying malignancy
Total bilirubin < 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
Adequate hematologic status, defined as:
Absolute neutrophil count (ANC) ≥1.5 × 109/L not requiring growth factor support for at least 7 days prior to Screening, and
Platelet count ≥100.0×109/L not requiring transfusion support for at least 7 days prior to Screening
Able to provide informed consent or have a legal representative able and willing to do so
Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion; this may include barrier methods such as condom or diaphragm with spermicidal gel.

Exclusion Criteria

Known, actionable oncogenic driver mutation other than NRG1 fusion where available standard therapy is indicated
Life expectancy < 3 months
Pregnant or lactating
Prior treatment with ERBB3/HER3 directed therapy (Cohort 1 only)
Prior treatment with pan-ERBB or any ERBB/HER2/HER3 directed therapy (Cohort 1 only)
Symptomatic or untreated brain metastases (Note: Patients with asymptomatic brain metastases treated with radiation or surgery and without evidence of progression by imaging at screening are eligible to participate in the study. Patients requiring ongoing corticosteroids to treat brain metastases will not be eligible).
Received other investigational agent or anticancer therapy within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter
Prior to initiation of seribantumab treatment, patients must have recovered from clinically significant toxicities from prior anticancer or investigational therapy
Any other active malignancy requiring systemic therapy
Known hypersensitivity to any of the components of seribantumab or previous CTCAE grade 3 or higher hypersensitivity reactions to fully human monoclonal antibodies
Clinically significant cardiac disease, including symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 12 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
Active uncontrolled systemic bacterial, viral, or fungal infection
Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3	Seribantumab	Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions lacking an EGF-like domain, who have received prior standard treatment, which may have included prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.
Cohort 1	Seribantumab	A minimum of 55 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, excluding prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.
Cohort 2	Seribantumab	Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, including prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Up to 12 months	Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1, for seribantumab monotherapy (3,000 mg QW) in patients with centrally confirmed NRG1 fusion.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (42): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
William Osler Health System
🇨🇦
Brampton, Ontario, Canada
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Utah Cancer Specialists
🇺🇸
Salt Lake City, Utah, United States
Hawaii Cancer Care
🇺🇸
Honolulu, Hawaii, United States
Linear Clinical Research Ltd.
🇦🇺
Nedlands, Western Australia, Australia
Metro Minnesota CCOP
🇺🇸
Saint Louis Park, Minnesota, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
Peter MacCallum Cancer Centre
🇦🇺
Melbourne, Victoria, Australia
BC Cancer
🇨🇦
Vancouver, British Columbia, Canada
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
HonorHealth
🇺🇸
Scottsdale, Arizona, United States
Sanford Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Medical Oncology Hematology Consultants
🇺🇸
Newark, Delaware, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States
Georgetown University
🇺🇸
Washington, District of Columbia, United States
Royal Hobart Hospital
🇦🇺
Hobart, Tasmania, Australia
ThedaCare Regional Cancer Center
🇺🇸
Appleton, Wisconsin, United States
University of Colorado Denver
🇺🇸
Denver, Colorado, United States
Henry Ford
🇺🇸
Detroit, Michigan, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
Pacific Shores Medical Group
🇺🇸
Huntington Beach, California, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Compassionate Care Research Group Inc.
🇺🇸
Fountain Valley, California, United States
University of California - Irvine Medical Center
🇺🇸
Orange, California, United States
University Cancer And Blood Center
🇺🇸
Athens, Georgia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Penn State Health Hershey Medical Center Cancer Institute
🇺🇸
Hershey, Pennsylvania, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸
Fairfax, Virginia, United States
Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
🇺🇸
Blacksburg, Virginia, United States
Northwest Medical Specialties, PLLC
🇺🇸
Tacoma, Washington, United States
St. Vincent's Hospital
🇦🇺
Sydney, New South Wales, Australia
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Montefiore Medical Center
🇺🇸
Bronx, New York, United States