Testing AZD9291 as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH-Subprotocol E)

NCT ID: NCT06303167

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-08
• Study Completion Date: 2025-12-31

Brief Summary

This phase II MATCH treatment trial evaluates the effectiveness of osimertinib (AZD9291) in treating patients with cancer that has certain genetic changes called EGFR mutations. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of mutant forms of the EGFR protein, which play a key role in tumor cell growth. Osimertinib may cause tumor cell death and inhibit tumor growth in EGFR-overexpressing tumor cells, thereby stopping or slowing the spread of tumor cells.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive osimertinib (AZD9291) orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (osimertinib)

Patients receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or MUGA during screening, and biopsy and collection of blood samples on trial and at end of treatment.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA

Osimertinib

Intervention Type: DRUG

Given PO

Radiologic Examination

Intervention Type: PROCEDURE

Undergo radiologic evaluation

Interventions

Biopsy Procedure

Undergo biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Echocardiography Test

Undergo ECHO

Intervention Type: PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type: PROCEDURE

Osimertinib

Given PO

Intervention Type: DRUG

Radiologic Examination

Undergo radiologic evaluation

Intervention Type: PROCEDURE

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; EC; Echocardiography; Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; Gated Heart Pool Scan; MUGA; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Radionuclide Ventriculography; RNV Scan; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; AZD 9291; AZD-9291; AZD9291; Mereletinib; Radiologic Evaluation; Radiologic Exam

Eligibility Criteria

Inclusion Criteria

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
• Patient must fulfill all eligibility criteria outlined in MATCH Master Protocol at the time of registration to treatment step (step 1, 3, 5, 7)
• Patients must have either of the below, or another aberration, as determined via the MATCH Master Protocol:

• Any malignancy except non-small cell lung cancer (NSCLC) with EGFR T790M identified in their tumor, with or without an activating mutation OR
• Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, S786I or an EGFR exon 19 in frame insertion 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, and second-degree heart block
• Patients must have an ECHO or a nuclear study (MUGA or first pass) within 4 weeks prior to registration and must not have a 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
• Patients must not have known hypersensitivity to osimertinib (AZD9291) or compounds of similar chemical or biologic composition or any of the inactive excipients of the tablets
• Patient must not have received osimertinib (AZD9291), WZ4002, CO-1686, HM61713, EGF816 or ASP8273 previously
• Patients known to harbor germline EGFR T790M mutations are excluded from the study. Prospective testing for germline mutations is not required
• Patients must not have a history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, radiation pneumonitis requiring steroids, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Patients must not currently be receiving treatment with potent CYP3A4 inducters or medications "known to prolong" the QT interval. Drugs that "may possibly prolong" the QT interval, are permitted if the patient has been stable on therapy for the period indicated for the specific medication
• Patients must agree to not donate sperm from the start of protocol treatment until at least 4 months after the last dose of protocol treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lecia V Sequist

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

NCI-2024-01150

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-E

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-E

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01150

Identifier Type: -

Identifier Source: org_study_id