Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations (SUMMIT)

Puma Biotechnology

Status and phase: Terminated; Phase 2

Conditions: Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations

Treatments: Drug: Trastuzumab; Drug: Neratinib; Drug: Paclitaxel; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01953926

2013-002872-42 (EudraCT Number)

PUMA-NER-5201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 582 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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582 participants in 6 patient groups

Neratinib monotherapy

Experimental group

Description:

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.

Treatment:

Drug: Neratinib

Neratinib and Trastuzumab

Experimental group

Description:

Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.

Treatment:

Drug: Neratinib

Drug: Trastuzumab

Neratinib, Fulvestrant and Trastuzumab (Randomized)

Experimental group

Description:

Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.

Treatment:

Drug: Neratinib

Drug: Fulvestrant

Drug: Trastuzumab

Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)

Experimental group

Description:

Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.

Treatment:

Drug: Neratinib

Drug: Fulvestrant

Drug: Trastuzumab

Neratinib and Paclitaxel

Experimental group

Description:

Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.

Treatment:

Drug: Paclitaxel

Drug: Neratinib

Neratinib and Fulvestrant

Experimental group

Description:

Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.

Treatment:

Drug: Neratinib

Drug: Fulvestrant