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

Primary Purpose

Locally Advanced Solid Tumor, Metastatic Solid Tumor, Pancreatic Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Seribantumab
Sponsored by
Elevation Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Solid Tumor focused on measuring NRG1, Neuregulin 1, Gene fusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • HonorHealth
  • Compassionate Care Research Group Inc.
  • Pacific Shores Medical Group
  • Cedars-Sinai Medical Center
  • University of California - Irvine Medical Center
  • University of Colorado Denver
  • Medical Oncology Hematology Consultants
  • Georgetown University
  • Moffitt Cancer Center
  • University Cancer And Blood Center
  • Hawaii Cancer Care
  • Northwestern University
  • Massachusetts General Hospital Cancer Center
  • Henry Ford
  • Metro Minnesota CCOP
  • Washington University School of Medicine
  • Nebraska Methodist Hospital
  • Montefiore Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Levine Cancer Institute
  • The Ohio State University
  • Oregon Health and Science University
  • Penn State Health Hershey Medical Center Cancer Institute
  • Fox Chase Cancer Center
  • Sanford Oncology Clinic
  • Sarah Cannon Research Institute
  • Texas Oncology-Baylor Charles A. Sammons Cancer Center
  • The University of Texas M.D. Anderson Cancer Center
  • Utah Cancer Specialists
  • Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
  • Virginia Cancer Specialists
  • Northwest Medical Specialties, PLLC
  • ThedaCare Regional Cancer Center
  • University of Wisconsin
  • St. Vincent's Hospital
  • Royal Hobart Hospital
  • Peter MacCallum Cancer Centre
  • Linear Clinical Research Ltd.
  • BC Cancer
  • William Osler Health System
  • Seoul National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
May 7, 2020
Last Updated
August 7, 2023
Sponsor
Elevation Oncology
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1. Study Identification

Unique Protocol Identification Number
NCT04383210
Brief Title
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
Official Title
CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 29, 2020 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Elevation Oncology

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Solid Tumor, Metastatic Solid Tumor, Pancreatic Cancer, Lung Cancer, Head and Neck Cancer, Breast Cancer, Kidney Cancer, Colorectal Cancer, Bladder Cancer, Ovarian Cancer, Sarcoma, Gallbladder Cancer, Bile Duct Cancer, Esophageal Cancer, Uterine Cancer, Cholangiocarcinoma, Prostate Cancer
Keywords
NRG1, Neuregulin 1, Gene fusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Seribantumab
Intervention Description
Anti-HER3 monoclonal antibody
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Compassionate Care Research Group Inc.
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
Pacific Shores Medical Group
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92648
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of California - Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Colorado Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
Medical Oncology Hematology Consultants
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University Cancer And Blood Center
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Hawaii Cancer Care
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Henry Ford
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Metro Minnesota CCOP
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Health Hershey Medical Center Cancer Institute
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Sanford Oncology Clinic
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Texas Oncology-Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
The University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Oncology & Hematology Associates of Southwest Virginia Inc., DBA Blue Ridge Cancer Care
City
Blacksburg
State/Province
Virginia
ZIP/Postal Code
24060
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Northwest Medical Specialties, PLLC
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
ThedaCare Regional Cancer Center
City
Appleton
State/Province
Wisconsin
ZIP/Postal Code
54911
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
St. Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Linear Clinical Research Ltd.
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
BC Cancer
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
William Osler Health System
City
Brampton
State/Province
Ontario
ZIP/Postal Code
L6R 3J7
Country
Canada
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No

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

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