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.
* If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of FISH or next generation sequencing (NGS) status

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.
* If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of FISH or next generation sequencing (NGS) status
* If IHC is 3+, pt IS ELIGIBLE regardless of FISH or NGS status
* If IHC is 2+, FISH OR NGS must be positive for the patient to be ELIGIBLE. Otherwise, pt is NOT ELIGIBLE
* If IHC is unknown and…
* FISH is positive, independent of NGS results, the patient IS ELIGIBLE
* FISH is negative and NGS positive with ≥7 copies, the patient IS ELIGIBLE
* 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

Moyers, Justin

Co-Investigators

Andrew Hendifar, Bobbie Jo Rimel, Cathie T Chung, Inderjit Mehmi, Jun Gong, Kamya Sankar, Omid Hamid

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