Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
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.
Not Available
Phase II
Adults
Not Available
Not Available
Choe, Jennifer
National
Vanderbilt University
04-23-2025
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
Patients must have a HER2 amplified solid tumor except breast cancer. Patients 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, is allowed
One prior line of anti-HER2 therapy is allowed except tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib or antibody drug conjugates (ADC) such as DS8201a or T-DM1
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
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 Gilberts 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, Crohns 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
Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
Patients must have a HER2 amplified solid tumor except breast cancer. Patients 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, is allowed
One prior line of anti-HER2 therapy is allowed except tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib or antibody drug conjugates (ADC) such as DS8201a or T-DM1
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
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 Gilberts 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, Crohns 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
