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

Hematopoietic and Lymphoid Cell Neoplasm Clinical Trial

Official title:

MATCH Treatment Subprotocol E: Osimertinib (AZD9291) in Patients With Tumors Having EGFR T790M Mutations or Rare Activating Mutations of EGFR

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06303167
• Other study ID #: NCI-2024-01150
• Secondary ID: NCI-2024-01150EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 8, 2016
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: December 31, 2025
• Est. primary completion date: February 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

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

Intervention

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo blood sample collection
• Echocardiography
Undergo ECHO
• Multigated Acquisition Scan
Undergo MUGA

Drug:
• Osimertinib
Given PO

Procedure:
• Radiologic Examination
Undergo radiologic evaluation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

References & Publications (1)

Chen MF, Song Z, Yu HA, Sequist LV, Lovly CM, Mitchell EP, Moscow JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Umemura Y, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Stud — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	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	6-month Progression-Free Survival (PFS) Rate	Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression 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 detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.	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
Secondary	Progression Free Survival	PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression 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 detailed definitions of disease progression.	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