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

Breast Cancer Clinical Trial

Official title:

CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04383210
• Other study ID #: ELVCAP-001-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 29, 2020
• Est. completion date: March 2025

Study information

• Verified date: August 2023
• Source: Elevation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: March 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bile Duct Cancer
• Bile Duct Neoplasms
• Bladder Cancer
• Breast Cancer
• Cholangiocarcinoma
• Colorectal Cancer
• Esophageal Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Head and Neck Cancer
• Kidney Cancer
• Locally Advanced Solid Tumor
• Lung Cancer
• Metastatic Solid Tumor
• Neoplasms
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer
• Sarcoma
• Uterine Cancer
• Uterine Neoplasms

Intervention

Drug:
• Seribantumab
Anti-HER3 monoclonal antibody

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Elevation Oncology

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	The primary objective of this study is to determine the overall objective response rate (ORR) by independent radiologic review to single agent seribantumab in patients with NRG1 gene fusion positive advanced cancer according to RECIST 1.1	Up to 12 months