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
NCT ID: NCT03006172
Last Updated: 2025-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
200 participants
INTERVENTIONAL
2016-12-13
2026-12-31
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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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.
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).
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.
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).
Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
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.
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).
Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
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.
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).
Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
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.
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).
Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
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.
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).
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.
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.
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).
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.
Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
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.
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).
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.
Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Metformin
Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
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.
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).
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.
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.
Interventions
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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).
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.
Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
Palbociclib
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
Metformin
Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
Princess Margaret Hospital
Toronto, Ontario, Canada
Institut Bergonie
Bordeaux, , France
Institut Gustave Roussy
Villejuif, , France
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Royal Marsden Hospital - Surrey
Surrey, Sutton, United Kingdom
St Bartholomew's Hospital
London, , United Kingdom
Royal Marsden Hospital - London
London, , United Kingdom
Countries
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References
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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.
Other Identifiers
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GO39374
Identifier Type: -
Identifier Source: org_study_id
2016-003022-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-508124-36-00
Identifier Type: OTHER
Identifier Source: secondary_id