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

• ClinicalTrials.gov Identifier: NCT03006172
• Recruitment Status: Active, not recruiting
• First Posted: December 30, 2016
• Last Update Posted: March 28, 2024
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: December 22, 2016
• First Posted Date: December 30, 2016
• Last Update Posted Date: March 28, 2024
• Actual Study Start Date: December 13, 2016
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2021)

• 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 ]

Original Primary Outcome Measures (submitted: December 27, 2016)

• 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 GDC-0077 [ 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 3.5 years ]

Current Secondary Outcome Measures (submitted: March 19, 2021)

• 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 ]

Original Secondary Outcome Measures (submitted: December 27, 2016)

• Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cycle (Cy) 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to end of study (EOS). Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• AUC from Time Zero to Dosing Interval (AUC0-tau) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cycle (Cy) 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to end of study (EOS). Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Half-Life of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Maximum Plasma Concentration (Cmax) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Minimum Plasma Concentration (Cmin) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Time to Cmax (tmax) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Apparent Clearance (CL/F) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• Accumulation Ratio (AR) of GDC-0077 at Steady-State [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
• AUC of Palbociclib [ Time Frame: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days ]
• Cmax of Palbociclib [ Time Frame: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days ]
• AUC of Letrozole [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stages I and II, Arm B: 1 hr post GDC-0077 dose on Cy1 Days 1;predose on Cy 1 Day 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing. EOS=up to approximately 3.5 years; Cycle length=28 days
• Cmax of Letrozole [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
  Detailed timeframe: Stages I and II, Arm B: 1 hr post GDC-0077 dose on Cy1 Days 1;predose on Cy 1 Day 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing. EOS=up to approximately 3.5 years; Cycle length=28 days
• AUC of Fulvestrant [ Time Frame: Cy1 Day 2, predose on Days 8, 15, 22; Predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days. ]
• Cmax of Fulvestrant [ Time Frame: Cy1 Day 2, predose on Days 8, 15, 22; Predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 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 3.5 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 3.5 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 3.5 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 3.5 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 GDC-0077 Treatment [ Time Frame: Baseline, Week 2 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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)).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Solid Tumor

Intervention

• 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 Name: 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: 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.
• Drug: Metformin
  Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
• 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.

Study Arms

• 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.
  Intervention: Drug: Inavolisib
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Letrozole
  • Drug: Palbociclib
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Letrozole
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Letrozole
  • Drug: Palbociclib
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Letrozole
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Fulvestrant
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Fulvestrant
  • Drug: Palbociclib
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Fulvestrant
  • Drug: Palbociclib
  • Drug: Metformin
• 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Trastuzumab
  • Drug: Pertuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 8, 2020): 256
• Original Estimated Enrollment (submitted: December 27, 2016): 156
• Estimated Study Completion Date: November 30, 2024
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03006172
• Other Study ID Numbers: GO39374; 2016-003022-17 ( EudraCT Number ); 2023-508124-36-00 ( Other Identifier: EU CT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Hoffmann-La Roche
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: March 2024