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.
Primary- To determine the objective response rate by independent radiologic
review to single agent seribantumab (anti-HER3 targeted therapy) in
patients with centrally confirmed NRG1 gene fusion positive advanced
cancer according to RECIST 1.1.
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 post-enrollment confirmation of NRG1 gene fusion status (not a requirement for Cohorts 2 and 3)
Patients should have received a minimum of one prior standard therapy appropriate for their tumor type and stage of disease 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 per protocol
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; refer to protocol for more detailed criteria for men and women of reproductive potential.
Known, actionable oncogenic driver mutation other than NRG1 fusion where available standard therapy is indicated (Cohorts 1 and 2 only; not a requirement for Cohort 3)
Life expectancy > Pregnant or lactating
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, including those on a stable [i.e., same dose for > 2 weeks] low-dose corticosteroid regimen
Received other systemic or anticancer therapy (investigational or standard chemotherapy, immunotherapy, or
targeted therapy) within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter (Note: Patients may be included if they do not meet the above criteria if, in the opinion of the investigator, the patient has recovered from clinically significant toxicities from prior anticancer or investigational therapy.)
Prior to initiation of seribantumab treatment, patients must have recovered from clinically significant toxicities from prior anticancer or investigational therapy or acute radiation toxicities
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
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