Breast CancerPhase 1NCT03006172
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 1 study testing Inavolisib, Fulvestrant and Letrozole in people with Breast Cancer and Solid Tumor, run by Genentech, Inc. at 12 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Solid Tumor
- What is being tested?
- Inavolisib, Fulvestrant and Letrozole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 13 Dec 2016to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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.
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United States5 sites
Massachusetts General Hospital.
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
SCRI Oncology Partners
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10017
Columbia University Medical Center
New York, New York, 10032
France2 sites
Institut Bergonie
Bordeaux, 33076
Institut Gustave Roussy
Villejuif, 94805
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinico Universitario de Valencia
Valencia, 46010
United Kingdom2 sites
St Bartholomew's Hospital
London, EC1 A7BE
Royal Marsden Hospital - Surrey
Surrey, Sutton, SM2 5PT
About this study
Official title: 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
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
- Breast Cancer, Solid Tumor
- Being tested
- Inavolisib, Fulvestrant, Letrozole, Palbociclib, Metformin
- Keywords
- PIK3CA mutant, Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InavolisibDrug
Also called RO7113755, GDC-0077
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).
FulvestrantDrug
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.
LetrozoleDrug
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
PalbociclibDrug
Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
MetforminDrug
Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
TrastuzumabDrug
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.
PertuzumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Stage I Arm A: Inavolisib Single Agent | Experimental | 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. Receives: Drug: Inavolisib |
| Stage I Arm B: Inavolisib + Palbociclib + Letrozole | Experimental | 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. Receives: Drug: Inavolisib; Drug: Letrozole; Drug: Palbociclib |
| Stage I Arm C: Inavolisib + Letrozole | Experimental | 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. Receives: Drug: Inavolisib; Drug: Letrozole |
| Stage II Arm B: Inavolisib + Palbociclib + Letrozole | Experimental | 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. Receives: Drug: Inavolisib; Drug: Letrozole; Drug: Palbociclib |
| Stage II Arm C: Inavolisib + Letrozole | Experimental | 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. Receives: Drug: Inavolisib; Drug: Letrozole |
| Stage II Arm D: Inavolisib + Fulvestrant | Experimental | 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. Receives: Drug: Inavolisib; Drug: Fulvestrant |
| Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant | Experimental | 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. Receives: Drug: Inavolisib; Drug: Fulvestrant; Drug: Palbociclib |
| Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin | Experimental | 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. Receives: Drug: Inavolisib; Drug: Fulvestrant; Drug: Palbociclib; Drug: Metformin |
| Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab | Experimental | 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. Receives: Drug: Inavolisib; Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Percentage of Participants With Dose Limiting Toxicities
Measured: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
Recommended Phase II Dose of Inavolisib
Measured: 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
Measured: Day 1 up to 6 years
Secondary outcomes (23)
Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of Inavolisib
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Time to Cmax (tmax) of Inavolisib
Measured: 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)
Apparent Clearance (CL/F) of Inavolisib
Measured: 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)
Accumulation Ratio (AR) of Inavolisib at Steady-State
Measured: 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)
AUC of Palbociclib
Measured: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
Cmax of Palbociclib
Measured: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
AUC of Letrozole
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Cmax of Letrozole
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
AUC of Fulvestrant
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Cmax of Fulvestrant
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1)
Measured: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 6 years)
Duration of Response, as Assessed by RECIST v1.1
Measured: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1
Measured: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Progression Free Survival (PFS) as Assessed by RECIST v1.1
Measured: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of Inavolisib Treatment
Measured: Baseline, Week 2
AUC of Pertuzumab
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Cmax of Pertuzumab
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
AUC of Trastuzumab
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Cmax of Trastuzumab
Measured: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2016 (estimated)
- Study start13 Dec 2016
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03006172
- Sponsor's protocol ID
- GO39374
- Other IDs
- 2016-003022-17, 2023-508124-36-00, 2023, 2016
- Status last verified
- Sep 2026
- First submitted
- 22 Dec 2016
- Last updated
- 8 Sep 2026
- Results posted
- No
- Individual data sharing
- No
Publications
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.
PubMed 39236276
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03006172
- Acronym / sponsor ID
- GO39374
- Conditions
- Breast Cancer, Solid Tumor
- Keywords
- PIK3CA mutant, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2016 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 30 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Stage I Arm A: Inavolisib Single Agent | Experimental | Drug: InavolisibParticipants 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 | Experimental | Drug: Inavolisib, Drug: Letrozole, Drug: PalbociclibParticipants 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 | Experimental | Drug: Inavolisib, Drug: LetrozoleParticipants 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 | Experimental | Drug: Inavolisib, Drug: Letrozole, Drug: PalbociclibParticipants 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 | Experimental | Drug: Inavolisib, Drug: LetrozoleParticipants 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 | Experimental | Drug: Inavolisib, Drug: FulvestrantParticipants 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 | Experimental | Drug: Inavolisib, Drug: Fulvestrant, Drug: PalbociclibParticipants 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 | Experimental | Drug: Inavolisib, Drug: Fulvestrant, Drug: Palbociclib, Drug: MetforminParticipants 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 | Experimental | Drug: Inavolisib, Drug: Trastuzumab, Drug: PertuzumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InavolisibAlso: RO7113755, GDC-0077Participants 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). | Drug | Stage I Arm A: Inavolisib Single Agent, Stage I Arm B: Inavolisib + Palbociclib + Letrozole, Stage I Arm C: Inavolisib + Letrozole, Stage II Arm B: Inavolisib + Palbociclib + Letrozole, Stage II Arm C: Inavolisib + Letrozole, Stage II Arm D: Inavolisib + Fulvestrant, Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant, Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin, Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab |
| FulvestrantParticipants 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 | Stage II Arm D: Inavolisib + Fulvestrant, Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant, Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin |
| LetrozoleParticipants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle. | Drug | Stage I Arm B: Inavolisib + Palbociclib + Letrozole, Stage I Arm C: Inavolisib + Letrozole, Stage II Arm B: Inavolisib + Palbociclib + Letrozole, Stage II Arm C: Inavolisib + Letrozole |
| PalbociclibParticipants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle. | Drug | Stage I Arm B: Inavolisib + Palbociclib + Letrozole, Stage II Arm B: Inavolisib + Palbociclib + Letrozole, Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant, Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin |
| MetforminParticipants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated. | Drug | Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin |
| TrastuzumabParticipants 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 | Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab |
| PertuzumabParticipants 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. | Drug | Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab |
Primary outcome
Stage 1: Percentage of Participants With Dose Limiting Toxicities
Time frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
Recommended Phase II Dose of Inavolisib
Time frame: 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
Time frame: Day 1 up to 6 years
23 secondary outcomes
Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of Inavolisib
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time to Cmax (tmax) of Inavolisib
Time frame: 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)
Apparent Clearance (CL/F) of Inavolisib
Time frame: 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)
Accumulation Ratio (AR) of Inavolisib at Steady-State
Time frame: 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)
AUC of Palbociclib
Time frame: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
Cmax of Palbociclib
Time frame: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
AUC of Letrozole
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Cmax of Letrozole
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
AUC of Fulvestrant
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Cmax of Fulvestrant
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1)
Time frame: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 6 years)
Duration of Response, as Assessed by RECIST v1.1
Time frame: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1
Time frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Progression Free Survival (PFS) as Assessed by RECIST v1.1
Time frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of Inavolisib Treatment
Time frame: Baseline, Week 2
AUC of Pertuzumab
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Cmax of Pertuzumab
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
AUC of Trastuzumab
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Cmax of Trastuzumab
Time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Derived from this study: PubMed 39236276Jhaveri 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Inavolisib, Fulvestrant and Letrozole in people with Breast Cancer and Solid Tumor, run by Genentech, Inc. at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, France, Spain, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Percentage of Participants With Dose Limiting Toxicities (time frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03006172, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.