Dataset Information

Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F.

ABSTRACT:

Purpose

Activating mutations in PIK3CA are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations (with or without PTEN loss).

Patients and methods

Patients received copanlisib (60 mg intravenous) once weekly on days 1, 8, and 15 in 28-day cycles until progression or toxicity. Patients with KRAS mutations, human epidermal growth factor receptor 2-positive breast cancers, and lymphomas were excluded. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival, 6-month progression-free survival, and overall survival.

Results

Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the Protocol. Multiple histologies were enrolled, with gynecologic (n = 6) and gastrointestinal (n = 6) being the most common. Sixty-eight percent of patients had ≥ 3 lines of prior therapy. The ORR was 16% (4 of 25, 90% CI, 6 to 33) with P = .0341 against a null rate of 5%. The most common reason for protocol discontinuation was disease progression (n = 17, 68%). Grade 3/4 toxicities observed were consistent with reported toxicities for PI3K pathway inhibition. Sixteen patients (53%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity (CTCAE v5.0). Most common toxicities include hyperglycemia (n = 19), fatigue (n = 12), diarrhea (n = 11), hypertension (n = 10), and nausea (n = 10).

Conclusion

The study met its primary end point with an ORR of 16% (P = .0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting.

SUBMITTER: Damodaran S

PROVIDER: S-EPMC9084438 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Phase II Study of Copanlisib in Patients With Tumors With <i>PIK3CA</i> Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F.

Damodaran Senthil S Zhao Fengmin F Deming Dustin A DA Mitchell Edith P EP Wright John J JJ Gray Robert J RJ Wang Victoria V McShane Lisa M LM Rubinstein Larry V LV Patton David R DR Williams P Mickey PM Hamilton Stanley R SR Suga Jennifer M JM Conley Barbara A BA Arteaga Carlos L CL Harris Lyndsay N LN O'Dwyer Peter J PJ Chen Alice P AP Flaherty Keith T KT

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20220208 14

<h4>Purpose</h4>Activating mutations in <i>PIK3CA</i> are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with <i>PIK3CA</i> mutations (with or without <i>PTEN</i> loss).<h4>Patients and methods</h4>Patients received copanlisib (60 mg intravenous) ...[more]

PMID: 35133871

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