Testing Afatinib as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH - Subprotocol A)

NCT06385483 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2024-01125EAY131-AU10CA180820
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial tests how well afatinib works in treating patients with cancer that has certain genetic changes. Afatinib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the EGFR gene. It works by blocking the action of mutated EGFR that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Conditions

Advanced Malignant Solid Neoplasm; Refractory Multiple Myeloma; Advanced Lymphoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-month Progression Free Survival (PFS)

  Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined

• Progression Free Survival

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (afatinib)

EXPERIMENTAL

Patients receive afatinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Drug: Afatinib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Radionuclide Imaging

Interventions

Radionuclide Imaging PROCEDURE

Undergo nuclear study

Also known as: Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, Scintigraphy

Treatment (afatinib)

Afatinib DRUG

Given PO

Also known as: BIBW 2992, BIBW-2992, BIBW2992

Treatment (afatinib)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (afatinib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (afatinib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (afatinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (afatinib)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (afatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
• Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
• Patient's tumor must have either of the below, or another aberration, as determined via the MATCH Master Protocol:
• Activating mutations of EGFR (del 19, L858R) OR
• Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, EGFR S768I
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
• Patients with known left ventricular dysfunction must have ECHO or a nuclear study (multigated acquisition scan \[MUGA\] or first pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) \< institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \> 50% for the patient to be eligible
• NOTE: Pre-treatment LVEF determination in patients without known left ventricular dysfunction is NOT otherwise required
• Patients must not have known hypersensitivity to afatinib or compounds of similar chemical or biologic composition
• Patients must have =\< grade 1 renal function as defined below:
• Creatinine =\< 1.5 x normal institutional limits OR
• Measured creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal or as calculated by the Cockcroft-Gault equation
• The above renal eligibility criteria should be strictly followed and will override the MATCH Master Protocol requirements
• Patients must not have had prior treatment with an EGFR tyrosine kinase inhibitor (TKI) (e.g. afatinib, erlotinib, gefitinib, neratinib, dacomitinib, AZD9291, cabertinib, CO-1686)
• Patients with non-small cell lung cancer and small cell lung cancer will be excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Afatinib; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Nuclear Medicine Department, Hospital

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Hospital Administration; Health Facility Administration; Organization and Administration; Health Services Administration

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Cancer Research Group

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Scott N Gettinger

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 26, 2024
• Study Start: February 28, 2018
• Primary Completion: December 6, 2022
• Study Completion (Estimated): January 15, 2027
• Last Updated: May 28, 2026
• Results First Posted: December 10, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)