NCT06126276From ClinicalTrials.govRecruiting

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

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

Malignant Female Reproductive System Neoplasm
Malignant Solid Neoplasm
Recurrent Malignant Female Reproductive System Neoplasm
Recurrent Malignant Solid Neoplasm

At a glance

Phase: Phase 2
Study type: Interventional
Sponsor: National Cancer Institute (NCI)
Enrolment target: 70
Started: 7 May 2024
Main results due: 20 February 2027
Study sites: 194
Registry updated: 23 September 2026

Can you take part?

Aged 18 years and over.
Open to any sex.
You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full 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.

  * 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

What this study is about

In the sponsor’s own words, from the registry.

This phase II ComboMATCH treatment trial compares the effect of neratinib to the combination of neratinib and palbociclib in treating patients with HER2 positive solid tumors. Neratinib and palbociclib are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving neratinib and palbociclib in combination may shrink or stabilize cancers that over-express a specific biomarker called HER2.

Study sites(194)

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Recruiting
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Recruiting
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Recruiting
UC San Diego Health System - Encinitas
Encinitas, California, United States
Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, United States
Recruiting
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, United States
Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, United States
Recruiting
UC San Diego Medical Center - Hillcrest
San Diego, California, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
Recruiting
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Recruiting
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States
Recruiting
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Recruiting
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, United States
Recruiting
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Recruiting
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, United States
Recruiting
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, United States
Recruiting
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, United States
Recruiting
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, United States
Recruiting
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States
Recruiting
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States
Recruiting
SIH Cancer Institute
Carterville, Illinois, United States
Recruiting
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, United States
Suspended
University of Illinois
Chicago, Illinois, United States
Active, not recruiting
Carle at The Riverfront
Danville, Illinois, United States
Recruiting
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Recruiting
Decatur Memorial Hospital
Decatur, Illinois, United States
Recruiting
Carle Physician Group-Effingham
Effingham, Illinois, United States
Recruiting
Crossroads Cancer Center
Effingham, Illinois, United States
Recruiting
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
Recruiting
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, United States
Recruiting
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, United States
Recruiting
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Recruiting
Carle BroMenn Medical Center
Normal, Illinois, United States
Recruiting
Carle Cancer Institute Normal
Normal, Illinois, United States
Recruiting
Cancer Care Center of O'Fallon
O'Fallon, Illinois, United States
Recruiting
Mercyhealth Cancer Institute - Rockford
Rockford, Illinois, United States
Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Recruiting
Springfield Clinic
Springfield, Illinois, United States
Recruiting
Springfield Memorial Hospital
Springfield, Illinois, United States
Recruiting
Carle Cancer Center
Urbana, Illinois, United States
Recruiting
Woodland Cancer Care Center
Michigan City, Indiana, United States
Recruiting
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, United States
Recruiting
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, United States
Recruiting
CommonSpirit Saint Joseph Medical Center - East Lexington
Lexington, Kentucky, United States
Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Recruiting
Harold Alfond Center for Cancer Care
Augusta, Maine, United States
Recruiting
Lafayette Family Cancer Center-EMMC
Brewer, Maine, United States
Recruiting
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, United States
Recruiting
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Recruiting
UPMC Western Maryland
Cumberland, Maryland, United States
Recruiting

Showing 60 of 194 sites — filter to narrow it down. 182 of the 194 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT06126276. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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