Clinical Trials /

A Phase 2 Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Cancer

NCT04383210

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Cancer
  • 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 IDs

  • ORG STUDY ID: ELVCAP-001-01
  • NCT ID: NCT04383210

Conditions

  • Locally Advanced Solid Tumor
  • Metastatic Solid Tumor

Interventions

DrugSynonymsArms
SeribantumabCohort 1

Purpose

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 Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalA 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.
  • Seribantumab
Cohort 2ExperimentalUp 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.
  • Seribantumab
Cohort 3ExperimentalUp 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.
  • Seribantumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 12 months
Safety Issue:
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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Elevation Oncology

Trial Keywords

  • NRG1
  • Neuregulin 1
  • Gene fusion

Last Updated

May 7, 2020