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)

Roche

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Placebo; Drug: Fulvestrant; Drug: Palbociclib; Drug: Inavolisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04191499

2019-002455-42 (EudraCT Number)

WO41554

Details and patient eligibility

About

This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Enrollment: 325 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Confirmed diagnosis of HR+/HER2- breast cancer
• Metastatic or locally advanced disease not amenable to curative therapy
• Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
• Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
• Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
• Consent to provide fresh or archival tumor tissue specimen
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of > 6 months
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

• Metaplastic breast cancer
• Any history of leptomeningeal disease or carcinomatous meningitis
• Any prior systemic therapy for metastatic breast cancer
• Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
• Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible
• Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
• Symptomatic active lung disease, or requiring daily supplemental oxygen
• History of inflammatory bowel disease or active bowel inflammation
• Anti-cancer therapy within 2 weeks before study entry
• Investigational drug(s) within 4 weeks before randomization
• Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
• Chronic corticosteroid therapy or immunosuppressants
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment
• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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325 participants in 2 patient groups, including a placebo group

Inavolisib + Palbociclib + Fulvestrant

Experimental group

Description:

Participants will receive inavolisib, palbociclib, and fulvestrant.

Treatment:

Drug: Inavolisib

Drug: Palbociclib

Drug: Fulvestrant

Placebo + Palbociclib + Fulvestrant

Placebo Comparator group

Description:

Participants will receive placebo, palbociclib, and fulvestrant.

Treatment:

Drug: Palbociclib

Drug: Fulvestrant

Drug: Placebo