Inavolisib Combo Meets Primary End Point in PIK3CA-Mutated Breast Cancer


An experimental drug combination of inavolisib, palbociclib, and fulvestrant significantly improved progression-free survival in patients with HR-positive/HER2-negative PIK3CA-mutated breast cancer.

Breast Cancer Image: © Giovanni Cancemi-

Breast Cancer Image: © Giovanni Cancemi-

The combination of inavolisib (GDC-0077) with palbociclib (Ibrance) and fulvestrant in the first line demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs palbociclib and fulvestrant alone in patients with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer, meeting the primary end point of the phase 3 INAVO120 study (NCT04191499).1

At this time, overall survival data are immature. However, there was a clear positive trend observed. For safety, the combination with inavolisib was well-tolerated and adverse events (AEs) were consistent with the known safety profiles of each individual agent. No new safety signals were identified.

Follow-up will continue to the next analysis. In addition, data will be shared with health authorities, as well as presented at an upcoming medical meeting.

“These pivotal study results for this inavolisib combination could represent a transformative medical advance for people with PIK3CA-mutated HR-positive breast cancer,” said Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of Global Product Development, in a press release. “We look forward to expanding our portfolio of breast cancer medicines into the HR-positive space and bringing this potentially best-in-class new treatment option to patients as quickly as possible.”


The randomized, double-blind, placebo-controlled, phase 3 INAVO120 study is evaluating the safety and efficacy of inavolisib combined with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. Enrollment is open to patients whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy. Patients also must not have received prior systemic therapy for their disease.2

Additional enrollment criteria noted that patients must have received LHRH agonist therapy for at least 2 weeks prior to day 1 of cycle 1 if pre/perimenopausal, confirmation of biomarker eligibility, measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, a life expectancy of > 6 months, and adequate hematologic and organ function within 14 days prior to initiation of study treatment.

A total of 325 patients aged 18 years and older were randomly assigned to receive either the investigational or control treatment arm and evaluated for the primary end point of PFS, as assessed by investigators. PFS was defined as the time from randomization in the trial to the time when the disease progresses, or a patient dies from any cause. Further, investigators evaluated the secondary end points of overall survival, objective response rate, and clinical benefit rate.1,2

About Inavolisib

Inavolisib is an oral treatment that is characterized by its high in vitro potency and selectivity for inhibiting PI3Kα. The agent has the ability to specifically induce the degradation of mutant PI3Kα protein. Inavolisib’s unique dual mechanism of action may provide well-tolerated, durable disease control for patients with HR-positive/HER2-negative, PIK3CA-mutated advanced breast cancer and potentially can improve outcomes.1

In addition to INAVO120, inavolisib is currently undergoing investigation in the phase 3 INAVO121 (NCT05646862) and INAVO122 studies in various combinations for patients with PIK3CA-mutated metastatic breast cancer.

  1. Genentech announces positive phase III results for inavolisib combination in people with advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. News release. Genentech. December 4, 2023. Accessed December 5, 2023.
  2. A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer (INAVO120). Updated November 18, 2023. Accessed December 5, 2023.
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