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

August 7, 2023 updated by: Elevation Oncology

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2010
        • St. Vincent's Hospital
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Royal Hobart Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Linear Clinical Research Ltd.
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health System
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • HonorHealth
    • California
      • Fountain Valley, California, United States, 92708
        • Compassionate Care Research Group Inc.
      • Huntington Beach, California, United States, 92648
        • Pacific Shores Medical Group
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Orange, California, United States, 92868
        • University of California - Irvine Medical Center
    • Colorado
      • Denver, Colorado, United States, 80220
        • University of Colorado Denver
    • Delaware
      • Newark, Delaware, United States, 19713
        • Medical Oncology Hematology Consultants
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer and Blood Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota CCOP
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Health Hershey Medical Center Cancer Institute
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Oncology Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
      • Houston, Texas, United States, 77030
        • The University of Texas M.D. Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
    • Virginia
      • Blacksburg, Virginia, United States, 24060
        • Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
    • Washington
      • Tacoma, Washington, United States, 98405
        • NorthWest Medical Specialties, PLLC
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1

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.
Drug: Seribantumab
Anti-HER3 monoclonal antibody
Experimental: Cohort 2

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.
Drug: Seribantumab
Anti-HER3 monoclonal antibody
Experimental: Cohort 3

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.
Drug: Seribantumab
Anti-HER3 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: Up to 12 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Elevation Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2020

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

May 7, 2020

First Submitted That Met QC Criteria

May 7, 2020

First Posted (Actual)

May 12, 2020

Study Record Updates

Last Update Posted (Actual)

August 8, 2023

Last Update Submitted That Met QC Criteria

August 7, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ELVCAP-001-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcoma

Clinical Trials on Seribantumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe