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Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors
1 other identifier
interventional
54
4 countries
42
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2020
Typical duration for phase_2
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 7, 2020
CompletedFirst Posted
Study publicly available on registry
May 12, 2020
CompletedStudy Start
First participant enrolled
September 29, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2024
CompletedResults Posted
Study results publicly available
April 3, 2025
CompletedApril 3, 2025
March 1, 2025
3.4 years
May 7, 2020
February 28, 2025
March 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate
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.
Up to 12 months
Study Arms (3)
Cohort 1
EXPERIMENTALA 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
EXPERIMENTALUp 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.
Cohort 3
EXPERIMENTALUp 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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 Ă— upper limit of normal (ULN), or AST and ALT \< 5 Ă— 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 Ă— 109/L not requiring growth factor support for at least 7 days prior to Screening, and
- Platelet count ≥100.0Ă—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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (42)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
HonorHealth
Scottsdale, Arizona, 85258, United States
Compassionate Care Research Group Inc.
Fountain Valley, California, 92708, United States
Pacific Shores Medical Group
Huntington Beach, California, 92648, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California - Irvine Medical Center
Orange, California, 92868, United States
University of Colorado Denver
Denver, Colorado, 80220, United States
Medical Oncology Hematology Consultants
Newark, Delaware, 19713, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University Cancer And Blood Center
Athens, Georgia, 30607, United States
Hawaii Cancer Care
Honolulu, Hawaii, 96813, United States
Northwestern University
Chicago, Illinois, 60611, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Henry Ford
Detroit, Michigan, 48202, United States
Metro Minnesota CCOP
Saint Louis Park, Minnesota, 55416, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Penn State Health Hershey Medical Center Cancer Institute
Hershey, Pennsylvania, 17033, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Sanford Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
Blacksburg, Virginia, 24060, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405, United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
St. Vincent's Hospital
Sydney, New South Wales, 2010, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Linear Clinical Research Ltd.
Nedlands, Western Australia, 6009, Australia
BC Cancer
Vancouver, British Columbia, V5Z 4E6, Canada
William Osler Health System
Brampton, Ontario, L6R 3J7, Canada
Seoul National University Hospital
Seoul, 03080, South Korea
Related Publications (1)
Patil T, Lin JJ, Cheema PK, Carrizosa DR, Burkard ME, Elamin YY, Desai J, Patel JD, Nagasaka M, Reckamp KL, Waqar SN, Bauman JR, Schram AM, Gadgeel SM, Ma PC, Konduri K, Nguyen D, Misleh J, Bleeker J, Weiss M, Thavaneswaran S, Haura EB, Deegan M, Kaufman J, Srivastava J, Jansen VM, Liu SV. CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 (NRG1) Fusions. JCO Precis Oncol. 2025 Aug;9:e2500221. doi: 10.1200/PO-25-00221. Epub 2025 Dec 22.
PMID: 41428976DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information
- Organization
- Elevation Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 7, 2020
First Posted
May 12, 2020
Study Start
September 29, 2020
Primary Completion
February 28, 2024
Study Completion
February 28, 2024
Last Updated
April 3, 2025
Results First Posted
April 3, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share