Study overview

VIKTORIA-2 is a Phase 3 clinical trial evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer (ABC) who are endocrine therapy resistant. For the CDK4/6 inhibitor, investigators may choose either ribociclib or palbociclib.

Approximately 638 eligible patients whose PIK3CA mutational status has been determined will be enrolled.

Patients will be assigned to a cohort based on the PIK3CA status of their tumor (MT or WT) and then randomized on a 1:1 basis to receive either the investigational regimen of gedatolisib, a CDK4/6 inhibitor and fulvestrant (Arm 1) or the control regimen of a CDK4/6 inhibitor and fulvestrant (Arm 2).

Prior to initiating the Phase 3 study, a safety run-in of approximately 12-36 subjects will evaluate the safety profile of gedatolisib combined with ribociclib and fulvestrant. The safety profile of gedatolisib combined with fulvestrant and palbociclib has previously been characterized.

Study rationale

Patients with HR+/HER2- ABC, whose disease recurred while receiving or within 12 months of completing adjuvant endocrine treatment, receive only modest benefit from currently available therapies. These patients typically are treated with any one of three approved CDK4/6 inhibitors combined with fulvestrant.

The PI3K/AKT/mTOR (PAM), estrogen receptor, and CDK pathways are interdependent drivers of HR+/HER2- breast cancer. Simultaneous inhibition of the PAM pathway with gedatolisib, the CDK4/6 pathway with palbociclib or ribociclib, and the estrogen receptor pathway with fulvestrant, is thus intended to disrupt the complex cooperation between these pathways to inhibit tumor growth.

A Phase 1b trial reported promising preliminary efficacy in treatment naïve patients with HR+/HER2- ABC who were treated with gedatolisib, palbociclib and letrozole.

Key eligibility criteria

  • ER+/HER2- advanced or metastatic breast cancer
  • No prior treatment for advanced or metastatic breast cancer
  • Progression or relapse of disease during or within 12 months of completing adjuvant endocrine treatment

Primary Endpoint

  • Progression-free survival in PIK3CA WT patients enrolled in Cohort 1 (Arm 1 vs. Arm 2)

Spacer

  • Progression-free survival in PIK3CA MT patients enrolled in Cohort 2 (Arm 1 vs. Arm 2)

 

Study locations

VIKTORIA-2 will be conducted at sites in North America, Europe, South America, Australia, and Asia.

Gedatolisib

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