Neratinib Alone or in Combination with Palbociclib in HER2+ Cancers and Other Solid Tumors

What is the Purpose of this Study?

This study focuses on individuals who have recurrent or persistent cancer and whose cancer expresses a protein called HER2 (human growth factor receptor 2). The purpose of the study is to determine whether a combination of drugs, neratinib and palbociclib, is better than neratinib alone in preventing cancer progression. Participants will be randomly assigned to 1 of 2 groups. The first group will receive neratinib and Palbociclib; the second group will receive neratinib alone. The combined use of neratinib and palbociclib in this study is considered investigational.

Eligibility

* 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

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

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Where can I participate?

CS Cancer at Cedars-Sinai Medical Center : Shannon Cyhan
CS Cancer at The Angeles Clinic and Research Institute : Shannon Cyhan

More about this Clinical Trial

What is the full name of this clinical trial?

EAY191-N5: A Randomized Trial of Neratinib, A Pan-ERBB Inhibitor, Alone or in Combination with Palbociclib, a CDK4/6 Inhibitor, In PAtient with HER2+ Gynecologic Cancers and other Solid Tumors A ComboMATCH Treatment Trial

Study Details

Disease Type/Condition

Other Female Genital, Unknown Sites

Principal Investigator

Hafez, Navid

Co-Investigators

Andrew Hendifar, Bobbie Jo Rimel, Inderjit Mehmi, Jun Gong, Justin Moyers, Kamya Sankar, Omid Hamid, Vi K. Chiu

Age Group

Adult

Phase

IRB Number

STUDY00003764

ClinicalTrials.gov ID

NCT06126276

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Shannon Cyhan

Shannon.Cyhan@cshs.org