Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

Launched by NATIONAL CANCER INSTITUTE (NCI) · Nov 9, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of two treatments for patients with certain types of cancer known as HER2 positive solid tumors. The study compares a medication called neratinib to a combination of neratinib and another drug called palbociclib. Both drugs aim to block specific signals that help cancer cells grow, potentially slowing down or stopping the cancer from spreading. This trial is part of a larger research effort called ComboMATCH and is specifically designed for patients who have already participated in a previous study.

To be eligible for this trial, patients must be at least 18 years old and have a HER2 amplified solid tumor (not breast cancer) that either keeps coming back or has not gone away. They should also have measurable disease that can be safely biopsied or have recent tissue samples available. Participants will undergo treatment with either neratinib alone or the combination treatment, and they will be monitored closely for how well the drugs work and any side effects. It’s important for interested patients to discuss their individual situation with their doctor to see if they qualify for this trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N5 based on the presence of an actionable mutation as defined in EAY191
• • Patients must have a HER2 amplified solid tumor except breast cancer. Patient's cancer must have HER2 amplification as defined with ≥ 7 copies by next generation sequencing (NGS) testing
• • Patients must have recurrent or persistent disease
• • No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation
• • Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
• • Patients must have measurable disease based on RECIST 1.1. A second measurable lesion outside of the biopsiable lesion is required
• • Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression for 3 months or more and patient is not on steroids and is asymptomatic
• • No known leptomeningeal disease
• • Patients may have received up to 5 prior lines of systemic therapy
• • Prior therapy with trastuzumab or pertuzumab, either alone or in combination, antibody drug conjugates (ADC) such as DS8201a or T-DM1 is allowed
• • Prior therapy with tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib is not allowed
• • No prior therapy with CDK4/6 inhibition
• • No cancer directed therapy within 3 weeks prior to registration. For oral therapy, the washout can be reduced to greater than or equal to 5 half lives of the drug. No HER2 targeting ADCs within 30 days prior to registration
• • Age ≥ 18
• • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• • Not pregnant and not nursing
• • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
• • Platelets ≥ 100,000 cells/mm\^3
• • Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 9 g/dl is acceptable)
• • Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
• • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
• • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN)
• • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• • No active infection requiring parenteral antibiotics
• • No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
• • No current evidence of malabsorption or chronic diarrhea or any other significant gastro-intestinal disease (e.g gastrectomy, ileal bypass, Crohn's disease, gastroparesis), associated with moderate to severe diarrhea (grade 2 or more) or inability to tolerate oral therapy
• • No lung disease causing dyspnea at rest
• • No interstitial lung disease with ongoing signs and symptoms at the time of registration
• • No history of allergic reaction to the study agents, compound of similar chemical or biologic composition of the study agents or any of their excipients