Testing Afatinib as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol B)

NCT04439136 | Active Not Recruiting Phase 2 Results DMC

• 4 other identifiers: NCI-2020-03140EAY131-BU10CA180820U24CA196172
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial identifies the effects of afatinib in patients whose cancer has genetic changes called HER2 mutations. Afatinib may stop the growth of cancer cells by blocking the HER2 receptor, a protein that may be needed for cell growth. Researchers hope to learn if afatinib will shrink this type of cancer or stop its growth.

Conditions

Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the 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. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was 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) Rate

  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 (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

Study Arms (1)

Treatment (afatinib dimaleate)

EXPERIMENTAL

Patients receive afatinib dimaleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Afatinib Dimaleate

Interventions

Afatinib Dimaleate DRUG

Given PO

Also known as: (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate), BIBW 2992MA2, BIBW2992 MA2, Gilotrif

Treatment (afatinib dimaleate)

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 prior to registration to treatment subprotocol
• Patient's tumor must have activating HER2 mutation, as determined via the MATCH Master Protocol
• Additionally, any in-frame insertions in exon 20 will be considered an activating mutation
• 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 echocardiogram (ECHO) or a nuclear study (multiple-gated acquisition \[MUGA\] 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 have =\< grade 1 diarrhea at baseline
• 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
• This should be strictly followed and will override the MATCH Master Protocol requirements

You may not qualify if:

• Patients must not have known hypersensitivity to afatinib or compounds of similar chemical or biologic composition
• Patients with a history of interstitial lung disease will be excluded
• Patients must not have had prior treatment with any of the following tyrosine kinase inhibitors (TKIs), which have known activity against HER2 kinase:
• Neratinib
• AC-480 (BMS-599626)
• AST 1306
• Canertinib (CI 1033)
• CUDC-101
• Lapatinib
• TAK285
• Afatinib
• AEE 788
• AZD8931
• CP-724714
• Dacomitinib

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma; Multiple Myeloma

Interventions

Afatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Philippe L Bedard

  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: June 18, 2020
• First Posted: June 19, 2020
• Study Start: August 12, 2015
• Primary Completion: January 22, 2021
• Study Completion (Estimated): March 3, 2027
• Last Updated: April 29, 2026
• Results First Posted: November 29, 2022

Record last verified: 2026-03

Locations

US (1)