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.
Title
- Brief Title: Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
- Official Title: An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
Clinical Trial IDs
- ORG STUDY ID:
PUMA-NER-5201
- SECONDARY ID:
2013-002872-42
- NCT ID:
NCT01953926
Conditions
- Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Interventions
Drug | Synonyms | Arms |
---|
Neratinib | Nerlynx | Neratinib and Trastuzumab |
Fulvestrant | Faslodex | Neratinib, Fulvestrant and Trastuzumab (Non-Randomized) |
Trastuzumab | Herceptin | Neratinib and Trastuzumab |
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Neratinib monotherapy | Experimental | Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations. | |
Neratinib and Trastuzumab | Experimental | Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. | |
Neratinib, Fulvestrant and Trastuzumab (Randomized) | Experimental | Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers. | - Neratinib
- Fulvestrant
- Trastuzumab
|
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized) | Experimental | Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers. | - Neratinib
- Fulvestrant
- Trastuzumab
|
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Confirmed Objective Response Rate (Breast, Cervical Cohorts) |
Time Frame: | From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months |
Safety Issue: | |
Description: | Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts) |
Secondary Outcome Measures
Measure: | Progression-Free Survival (PFS) |
Time Frame: | From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 18 months |
Safety Issue: | |
Description: | Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy |
Measure: | Confirmed Objective Response Rate (Other Cohorts) |
Time Frame: | From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months |
Safety Issue: | |
Description: | Percentage of participants who are confirmed by independent central review to have achieved CR or PR according to RECIST v1.1 (all other cohorts) |
Measure: | Objective Response Rate - First Tumor Assessment (Breast, Cervical Cohorts) |
Time Frame: | From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks |
Safety Issue: | |
Description: | Percentage of participants who achieve CR or PR according to RECIST v1.1, or other defined response criteria, at the first scheduled tumor assessment (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts) |
Measure: | Clinical Benefit Rate (CBR) |
Time Frame: | From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 18 months |
Safety Issue: | |
Description: | Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment |
Measure: | Duration of Response (DOR) |
Time Frame: | From first response to first disease progression or death, assessed up to 18 months |
Safety Issue: | |
Description: | Time from which measurement criteria are met for confirmed overall response of CR or PR (whichever status is recorded first) until the first date of documented disease progression |
Measure: | Overall Survival (OS) |
Time Frame: | From enrollment date to death, assessed up to two years |
Safety Issue: | |
Description: | Time from Cycle 1 Day 1 to death due to any cause |
Measure: | Incidence of Treatment-Emergent Adverse Events |
Time Frame: | From first dose through 28 days after the last dose, assessed up to 18 months |
Safety Issue: | |
Description: | Treatment-emergent and serious adverse events that occurred on or after first dose of investigational product and up to 28 days after the last dose |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Puma Biotechnology, Inc. |
Trial Keywords
- Neratinib
- Nerlynx
- Breast
- Solid Tumors
- Cancer
- HER2 mutations
- EGFR mutations
- Fulvestrant
- Trastuzumab
- Cervical
- Salivary
- ERBB2
- Exon 18
- Metastatic
- HR Positive
- Lung
- Non-Small Cell Lung Cancer (NSCLC)
Last Updated
July 22, 2021