Bile Duct Cancer, Bladder Cancer, Breast Cancer, Cholangiocarcinoma, Colorectal Cancer, Esophageal Cancer, Gallbladder Cancer, Head and Neck Cancer, Kidney Cancer, Locally Advanced Solid Tumor, Lung Cancer, Metastatic Solid Tumor, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Sarcoma, Uterine Cancer
Conditions
Keywords
NRG1, Neuregulin 1, Gene fusion
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.
Interventions
DRUGSeribantumab
Anti-HER3 monoclonal antibody
Sponsors
Elevation Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 12 months | Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1, for seribantumab monotherapy (3,000 mg QW) in patients with centrally confirmed NRG1 fusion. |
Countries
Australia, Canada, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Enrolled 36 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: Anti-HER3 monoclonal antibody | 36 |
| Cohort 2 Enrolled 11 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: Anti-HER3 monoclonal antibody | 11 |
| Cohort 3 Enrolled 7 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: Anti-HER3 monoclonal antibody | 7 |
| Total | 54 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 5 Participants | 4 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 6 Participants | 3 Participants | 30 Participants |
| Age, Continuous | 61 years | 59 years | 66 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 26 Participants | 6 Participants | 7 Participants | 39 Participants |
| Region of Enrollment Australia | 2 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment Canada | 2 participants | 2 participants | 0 participants | 4 participants |
| Region of Enrollment United States | 32 participants | 9 participants | 6 participants | 47 participants |
| Sex: Female, Male Female | 22 Participants | 7 Participants | 5 Participants | 34 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 2 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 36 | 8 / 11 | 7 / 7 |
| other Total, other adverse events | 35 / 36 | 11 / 11 | 7 / 7 |
| serious Total, serious adverse events | 17 / 36 | 6 / 11 | 4 / 7 |
Outcome results
Primary
Objective Response Rate
Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1, for seribantumab monotherapy (3,000 mg QW) in patients with centrally confirmed NRG1 fusion.
Time frame: Up to 12 months
Population: Among the 36 patients enrolled in Cohort 1, 29 of 36 patients met criteria (criteria includes centrally confirmed NRG1 fusion status and patient received 3,000 mg QW dosing) to be included in the primary efficacy population and were evaluable for investigator assessed response per RECIST v1.1. In Cohorts 2 and 3, one patient in each cohort was not evaluable for investigator assessed response per RECIST v1.1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Objective Response Rate | 10 Participants |
| Cohort 2 | Objective Response Rate | 1 Participants |
| Cohort 3 | Objective Response Rate | 0 Participants |