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Testing neratinib alone or with palbociclib for HER2 positive solid tumors

A Randomized Trial of Neratinib, A Pan-ERBB Inhibitor, Alone or in Combination With Palbociclib, a CDK4/6 Inhibitor, in Patients With HER2+ Gynecologic Cancers and Other Solid Tumors: A ComboMATCH Treatment Trial

Phase 2 Interventional National Cancer Institute (NCI) · NCT06126276

This study is testing if a new cancer treatment called neratinib works better alone or with another drug, palbociclib, for people with HER2 positive solid tumors, especially those with gynecologic cancers.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment70 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionstrastuzumab, pertuzumab, neratinib, tucatinib
Locations187 sites (Birmingham, Alabama and 186 other locations)
Trial IDNCT06126276 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of neratinib compared to a combination of neratinib and palbociclib in patients with HER2 positive solid tumors, particularly focusing on gynecologic cancers. The study aims to assess progression-free survival, objective response rates, and overall survival while monitoring adverse events. Patients will undergo biopsies and imaging tests to gather data on treatment response and tumor characteristics. The trial also explores the relationship between circulating tumor DNA and tumor tissue profiles to better understand treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates include patients with recurrent or persistent HER2 amplified solid tumors, excluding breast cancer, who have measurable disease and can provide a biopsy.

Not a fit: Patients with known RB1 loss or deletion, or those without HER2 amplification, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with HER2 positive solid tumors, potentially improving survival rates.

How similar studies have performed: Other studies have shown promise with similar targeted therapies, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion 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.

  * If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of in situ hybridization (ISH)/FISH or next generation sequencing (NGS) status
  * If IHC is 3+, pt IS ELIGIBLE regardless of ISH/FISH or NGS status
  * If IHC is 2+, ISH/FISH OR NGS must be positive for the patient to be ELIGIBLE. Otherwise, pt is NOT ELIGIBLE
  * If IHC is unknown and…

    * ISH/FISH is positive, independent of NGS results, the patient IS ELIGIBLE
    * ISH/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
* No prior therapy with HER2 targeting tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib
* 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

Where this trial is running

Birmingham, Alabama and 186 other locations

+137 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Malignant Female Reproductive System NeoplasmMalignant Solid NeoplasmRecurrent Malignant Female Reproductive System NeoplasmRecurrent Malignant Solid Neoplasm
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.