A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120)

• ClinicalTrials.gov Identifier: NCT04191499
• Recruitment Status: Active, not recruiting
• First Posted: December 9, 2019
• Last Update Posted: April 26, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: December 2, 2019
• First Posted Date: December 9, 2019
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: January 29, 2020
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 6, 2019): Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years) ]
• Original Primary Outcome Measures: Same as current

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

• Objective Response Rate (ORR) [ Time Frame: Up to 6 years ]
• Best Overall Response Rate (BOR) [ Time Frame: Up to 6 years ]
• Duration of Response (DOR) [ Time Frame: From the first occurrence of a CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years) ]
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 years ]
• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to 6 years) ]
• Time to Deterioration (TTD) in Pain [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Physical Function [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Role Function [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Global Health Status [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• Percentage of Participants with Adverse Events [ Time Frame: From randomization through the end of study (up to 6 years) ]
• Plasma Concentration of Inavolisib [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]
• Plasma Concentration of Palbociclib [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]
• Plasma Concentration of Fulvestrant [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]

Original Secondary Outcome Measures (submitted: December 6, 2019)

• Objective Response Rate (ORR) [ Time Frame: Up to 6 years ]
• Best Overall Response Rate (BOR) [ Time Frame: Up to 6 years ]
• Duration of Response (DOR) [ Time Frame: From the first occurrence of a CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years) ]
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 years ]
• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to 6 years) ]
• Time to Deterioration (TTD) in Pain [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Physical Function [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Role Function [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• TTD in Global Health Status [ Time Frame: Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days) ]
• Percentage of Participants with Adverse Events [ Time Frame: From randomization through the end of study (up to 6 years) ]
• Plasma Concentration of GDC-0077 [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]
• Plasma Concentration of Palbociclib [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]
• Plasma Concentration of Fulvestrant [ Time Frame: At pre-defined intervals from baseline to the end of study (up to 6 years) ]

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

Descriptive Information

• Brief Title: A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer
• Brief Summary: This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Inavolisib
  Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.
  Other Name: GDC-0077
• Drug: Placebo
  Participants will receive oral placebo on Days 1-28 of each 28-day cycle.
• Drug: Palbociclib
  Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.
• Drug: Fulvestrant
  Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Study Arms

• Experimental: Inavolisib + Palbociclib + Fulvestrant
  Participants will receive inavolisib, palbociclib, and fulvestrant.
  Interventions:

  • Drug: Inavolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Placebo Comparator: Placebo + Palbociclib + Fulvestrant
  Participants will receive placebo, palbociclib, and fulvestrant.
  Interventions:

  • Drug: Placebo
  • Drug: Palbociclib
  • Drug: Fulvestrant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 13, 2023): 325
• Original Estimated Enrollment (submitted: December 6, 2019): 400
• Estimated Study Completion Date: September 30, 2030
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of HR+/HER2- breast cancer
• Metastatic or locally advanced disease not amenable to curative therapy
• Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
• Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
• Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
• Consent to provide fresh or archival tumor tissue specimen
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of > 6 months
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

• Metaplastic breast cancer
• Any history of leptomeningeal disease or carcinomatous meningitis
• Any prior systemic therapy for metastatic breast cancer
• Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
• Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible
• Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
• Symptomatic active lung disease, or requiring daily supplemental oxygen
• History of inflammatory bowel disease or active bowel inflammation
• Anti-cancer therapy within 2 weeks before study entry
• Investigational drug(s) within 4 weeks before randomization
• Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
• Chronic corticosteroid therapy or immunosuppressants
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment
• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

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: Argentina, Australia, Belgium, Brazil, Canada, China, Denmark, France, Georgia, Germany, Greece, Hong Kong, Hungary, Italy, Korea, Republic of, Malaysia, New Zealand, Poland, Portugal, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Austria, Mexico

Administrative Information

• NCT Number: NCT04191499
• Other Study ID Numbers: WO41554; 2019-002455-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024