To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer
A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted Therapies in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Breast Cancer
3 other identifiers
interventional
200
5 countries
13
Brief Summary
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)).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 breast-cancer
Started Dec 2016
Longer than P75 for phase_1 breast-cancer
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 13, 2016
CompletedFirst Submitted
Initial submission to the registry
December 22, 2016
CompletedFirst Posted
Study publicly available on registry
December 30, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
March 11, 2026
March 1, 2026
10.1 years
December 22, 2016
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Stage 1: Percentage of Participants With Dose Limiting Toxicities
Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
Recommended Phase II Dose of Inavolisib
Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
Percentage of Participants With Adverse Events and Serious Adverse Events
Day 1 up to 6 years
Secondary Outcomes (23)
Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of Inavolisib
Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to end of study (EOS; up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
AUC from Time Zero to Dosing Interval (AUC0-tau) of Inavolisib
Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
Half-Life of Inavolisib
Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
Maximum Plasma Concentration (Cmax) of Inavolisib
Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
Minimum Plasma Concentration (Cmin) of Inavolisib
Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
- +18 more secondary outcomes
Study Arms (9)
Stage I Arm A: Inavolisib Single Agent
EXPERIMENTALParticipants 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.
Stage I Arm B: Inavolisib + Palbociclib + Letrozole
EXPERIMENTALParticipants 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.
Stage I Arm C: Inavolisib + Letrozole
EXPERIMENTALParticipants 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.
Stage II Arm B: Inavolisib + Palbociclib + Letrozole
EXPERIMENTALParticipants 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.
Stage II Arm C: Inavolisib + Letrozole
EXPERIMENTALParticipants 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.
Stage II Arm D: Inavolisib + Fulvestrant
EXPERIMENTALParticipants 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.
Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
EXPERIMENTALParticipants 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.
Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
EXPERIMENTALParticipants 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.
Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
EXPERIMENTALParticipants 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.
Interventions
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).
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.
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
- +2 more criteria
You may not qualify if:
- 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
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (13)
Massachusetts General Hospital.
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10017, United States
Columbia University Medical Center
New York, New York, 10032, United States
SCRI Oncology Partners
Nashville, Tennessee, 37203, United States
Princess Margaret Hospital
Toronto, Ontario, M5G2M9, Canada
Institut Bergonie
Bordeaux, 33076, France
Institut Gustave Roussy
Villejuif, 94805, France
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Royal Marsden Hospital - Surrey
Surrey, Sutton, SM2 5PT, United Kingdom
St Bartholomew's Hospital
London, EC1 A7BE, United Kingdom
Royal Marsden Hospital - London
London, SW3 6JJ, United Kingdom
Related Publications (1)
Jhaveri KL, Accordino MK, Bedard PL, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop IE, Oliveira M, Schmid P, Saura C, Turner NC, Varga A, Cheeti S, Hilz S, Hutchinson KE, Jin Y, Royer-Joo S, Peters U, Shankar N, Schutzman JL, Juric D. Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer. J Clin Oncol. 2024 Nov 20;42(33):3947-3956. doi: 10.1200/JCO.24.00110. Epub 2024 Sep 5.
PMID: 39236276DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 22, 2016
First Posted
December 30, 2016
Study Start
December 13, 2016
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
March 11, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share