Purpose

This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of inavolisib administered orally as a single agent in patients with locally advanced or metastatic PIK3CA-mutant solid tumors, including breast cancer, and in combination with standard-of-care endocrine and/or targeted therapies for the treatment of locally advanced or metastatic PIK3CA-mutant breast cancer. Participants will be enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II). Participants will be assigned to one of seven regimens: inavolisib as a single agent (Arm A), inavolisib in combination with palbociclib and letrozole (Arm B), inavolisib in combination with letrozole (Arm C), inavolisib in combination with fulvestrant (Arm D), inavolisib in combination with palbociclib and fulvestrant (Arm E), inavolisib in combination with palbociclib, fulvestrant, and metformin (Arm F), and inavolisib in combination with trastuzumab and pertuzumab (and letrozole or fulvestrant, if applicable (Arm G)).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Evaluable or measurable disease per RECIST, Version 1.1 (measurable disease only for Arm D) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy of greater than or equal to (>=) 12 weeks - Adequate hematologic and organ function, including blood counts, liver and kidney function Stage I Arm A (Inavolisib): - Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer Stages I and II, Arms B and C: - Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer Stage II, Arms D, E, or F: - Female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer Stage II Arm D: - Prior treatment with CDK4/6 inhibitor Stage II Arm G: - Female participants with locally advanced or metastatic PIK3CA-mutant HER2+ breast cancer - Left ventricular ejection fraction 50% or greater Stages I and II: - All participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation by central laboratory test.

Exclusion Criteria

  • Metaplastic breast cancer - History of leptomeningeal disease - Type 1 or 2 diabetes requiring anti-hyperglycemic medication - Inability or unwillingness to swallow pills - Malabsorption syndrome or other condition that would interfere with enteral absorption - Known and untreated, or active central nervous system metastases - Uncontrolled pleural effusion or ascites - Any active infection that could impact patient safety or serious infection requiring intravenous antibiotics - History of other malignancy within 5 years, except for treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer - History of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease - Congenital long QT syndrome, prolonged QT interval, or family history of sudden unexplained death or long QT syndrome Stage II Arms B, C, D, and E only: - Prior treatment with >1 chemotherapy regimen for metastatic disease - Prior treatment with PI3K inhibitor - History of significant toxicity related to mTOR inhibitor requiring treatment discontinuation Stage II Arms B and E only: - Prior CDK4/6 inhibitor treatment Stage II Arm G only: - Current uncontrolled hypertension or unstable angina - History of congestive heart failure, serious cardiac arrhythmia, or recent myocardial infarction - Prior ejection fraction decrease on trastuzumab - Prior cumulative doxorubicin greater than 360 mg/m2 - Symptomatic active lung disease - History of significant toxicity related to trastuzumab and/or pertuzumab requiring discontinuation of treatment

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Stage I Arm A: Inavolisib Single Agent
Participants will receive inavolisib in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of inavolisib on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
Experimental
Stage I Arm B: Inavolisib + Palbociclib + Letrozole
Participants will receive inavolisib in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1-21, and letrozole on Days 1-28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Letrozole
    Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
  • Drug: Palbociclib
    Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Experimental
Stage I Arm C: Inavolisib + Letrozole
Participants will receive inavolisib in escalating dose levels along with letrozole on Days 1-28 of each 28-day cycle. The starting dose of inavolisib will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Letrozole
    Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Experimental
Stage II Arm B: Inavolisib + Palbociclib + Letrozole
Participants will receive inavolisib on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Letrozole
    Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
  • Drug: Palbociclib
    Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Experimental
Stage II Arm C: Inavolisib + Letrozole
Participants will receive inavolisib in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Letrozole
    Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Experimental
Stage II Arm D: Inavolisib + Fulvestrant
Participants will receive inavolisib on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Fulvestrant
    Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.
Experimental
Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Fulvestrant
    Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.
  • Drug: Palbociclib
    Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Experimental
Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Fulvestrant
    Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.
  • Drug: Palbociclib
    Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
  • Drug: Metformin
    Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
Experimental
Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
Participants will receive inavolisib in combination with trastuzumab and pertuzumab (Days 1-21). Dose of inavolisib will be determined from the results of Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
    Other names:
    • RO7113755, GDC-0077
  • Drug: Trastuzumab
    Participants will receive trastuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles, until disease progression or unacceptable toxicity.
  • Drug: Pertuzumab
    Participants will receive pertuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 840 mg for Cycle 1 and a dose of 420 mg for subsequent cycles, until disease progression or unacceptable toxicity.

Recruiting Locations

Massachusetts General Hospital.
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: GO39374 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.