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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04383210




Registration number
NCT04383210
Ethics application status
Date submitted
7/05/2020
Date registered
12/05/2020
Date last updated
8/08/2023

Titles & IDs
Public title
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
Scientific title
CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
ELVCAP-001-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Solid Tumor 0 0
Metastatic Solid Tumor 0 0
Pancreatic Cancer 0 0
Lung Cancer 0 0
Head and Neck Cancer 0 0
Breast Cancer 0 0
Kidney Cancer 0 0
Colorectal Cancer 0 0
Bladder Cancer 0 0
Ovarian Cancer 0 0
Sarcoma 0 0
Gallbladder Cancer 0 0
Bile Duct Cancer 0 0
Esophageal Cancer 0 0
Uterine Cancer 0 0
Cholangiocarcinoma 0 0
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Seribantumab

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.

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.

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.


Treatment: Drugs: Seribantumab
Anti-HER3 monoclonal antibody
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Up to 12 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC,WA
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Linear Clinical Research Ltd. - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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California
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United States of America
State/province [4] 0 0
Colorado
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United States of America
State/province [5] 0 0
Delaware
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United States of America
State/province [6] 0 0
District of Columbia
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United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
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United States of America
State/province [10] 0 0
Illinois
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United States of America
State/province [11] 0 0
Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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Nebraska
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Dakota
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United States of America
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Tennessee
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United States of America
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Texas
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Utah
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United States of America
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Virginia
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United States of America
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Washington
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United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Elevation Oncology
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT04383210
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04383210