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

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, tucatinib, poziotinib) - 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

ArmDescriptionAssigned Intervention
Experimental
Neratinib monotherapy
Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, solid tumors (NOS) and lung cancers containing EGFR exon 18 mutations. Cohorts closed to enrollment in Amendment 6: gastroesophageal, biliary, ovarian, solid tumor (NOS) HER4 mutant, and fibrolamellar carcinoma.
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other names:
    • Nerlynx
Experimental
Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other names:
    • Nerlynx
  • Drug: Paclitaxel
    80mg/m^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
    Other names:
    • Taxol
Experimental
Neratinib and Trastuzumab
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in Amendment 6: colorectal, lung cancer HER2 mutant.
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other names:
    • Nerlynx
  • Drug: Trastuzumab
    Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
    Other names:
    • Herceptin
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.
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other names:
    • Nerlynx
  • Drug: Fulvestrant
    500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle
    Other names:
    • Faslodex
  • Drug: Trastuzumab
    Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
    Other names:
    • Herceptin
Experimental
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other names:
    • Nerlynx
  • Drug: Fulvestrant
    500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle
    Other names:
    • Faslodex
  • Drug: Trastuzumab
    Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
    Other names:
    • Herceptin

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35249

More Details

Status
Recruiting
Sponsor
Puma Biotechnology, Inc.

Study Contact

Puma Biotechnology, Inc. Clinical Operations Senior Director
(424) 248-6500
ClinicalTrials@pumabiotechnology.com

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 (for example HER2 mutant cervical cancer). 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 lasting for a maximum of 12 months for each participant after their last dose of neratinib or until initiation of additional anti-cancer therapy.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.