Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Purpose
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.
Condition
- Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Provide written informed consent - Histologically confirmed cancers for which no curative therapy exists - Documented HER2 or EGFR exon 18 mutation - Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol - At least one measurable lesion, defined by RECIST v1.1
Exclusion Criteria
- Participants harboring ineligible somatic HER2 mutations - Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible - Participants who are receiving any other anticancer agents - Symptomatic or unstable brain metastases - Women who are pregnant or breast-feeding There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Neratinib monotherapy |
Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations. Cohorts closed to enrollment in prior amendments: HER2 mutant cancers including bladder/urinary, colorectal, endometrial, breast HR-positive, TNBC HR-negative, lung, gastroesophageal, biliary, and ovarian; HER3 mutant solid tumor NOS; HER4 mutant solid tumor NOS; fibrolamellar carcinoma and EGFR brain. |
|
Experimental Neratinib and Trastuzumab |
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant. |
|
Experimental Neratinib, Fulvestrant and Trastuzumab (Randomized) |
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers. |
|
Experimental Neratinib, Fulvestrant and Trastuzumab (Non-Randomized) |
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers. |
|
Experimental Neratinib and Paclitaxel |
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers. |
|
Experimental Neratinib and Fulvestrant |
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers. |
|
More Details
- Status
- Terminated
- Sponsor
- Puma Biotechnology, Inc.
Study Contact
Detailed Description
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors. The study has a basket design and includes several cohorts, either defined by an actionable somatic mutation or by actionable mutation and tumor histology, including HER2 mutant breast, HER2 mutant cervical, HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers. The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 days after the last dose of neratinib and a survival follow-up period.