To Study the Effect of Inavolisib in Combination With Fulvestrant in Participants With Breast Cancer (optINAVO)

A Phase II, Randomized, Open-Label Study Evaluating Two Inavolisib Dose Levels in Combination With Fulvestrant in Participants With PIK3CA-Mutated, HR-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

The purpose of this study is to evaluate the efficacy and safety of inavolisib in combination with fulvestrant compared with inavolisib in combination with fulvestrant in participants with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer (LA/mBC) in the post-cyclin-dependent kinase inhibitor (CDKi) setting.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Inavolisib; Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WO46063 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
    • Recruiting
    • Centro Oncologico Korben
  • Córdoba, Argentina, 5016
    • Recruiting
    • Hospital Privado - Centro Medico de Córdoba
  • Rosario, Argentina, S2002KDS
    • Recruiting
    • Hospital Provincial del Centenario
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000KPG
      • Recruiting
      • Instituto de Oncologia de Rosario
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Recruiting
      • Blacktown Hospital
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Recruiting
      • Bendigo Cancer Centre
• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires St-Luc
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Zkh (Campus Virga Jesse)
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven Gasthuisberg
• Mexico
  • Mexico City, Mexico, 03100
    • Recruiting
    • CENEIT Oncologicos
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Recruiting
      • Hospital Civil de Guadalajara Fray Antonio Alcalde
    • Guadalajara, Jalisco, Mexico, 44680
      • Recruiting
      • RENATI INNOVATION S.A.P.I. de C.V
  • Querétaro
    • Queretaro Qro, Querétaro, Mexico, 76090
      • Recruiting
      • Centro de Infusion Tratamiento e Investigacion Oncologica S DE R
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron;Oncology
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario San Cecilio
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Recruiting
    • Adana Baskent University Hospital
  • Ankara, Turkey (Türkiye), 06520
    • Recruiting
    • Memorial Ankara Hastanesi
  • Seyhan, Turkey (Türkiye)
    • Recruiting
    • Medical Park Seyhan Hospital
  • Istanbul
    • Bağcılar, Istanbul, Turkey (Türkiye), 34214
      • Recruiting
      • Bagcilar Medipol Mega Universitesi Hastanesi
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Blackpool Victoria Hospital
  • Harlow, United Kingdom, CM20 1QX
    • Recruiting
    • Princess Alexandra Hospital
  • Northwood, Middlesex, United Kingdom, HA6 2RN
    • Recruiting
    • Mount Vernon Cancer Centre
• United States
  • California
    • Los Angeles, California, United States, 90017-4803
      • Recruiting
      • Los Angeles Cancer Network
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care East Brunswick

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented ER +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
• Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: <= 1 prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting
• Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
• Confirmation of biomarker eligibility: presence of >= 1 study-eligible PIK3CA mutation
• Life expectancy of > 6 months
• Ability, in the investigator's judgment, and willingness to comply with all study -related procedures, including completion of patient-reported outcomes

Exclusion Criteria:

• Metaplastic breast cancer
• Prior treatment with chemotherapy in the recurrent locally advanced/metastatic setting
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Prior treatment with PI3K/Akt/mTOR inhibitors in the recurrent locally advanced/metastatic setting
• Requirement for daily supplemental oxygen
• Symptomatic active lung disease, including pneumonitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inavolisib Dose A plus Fulvestrant; Participants will recieve an inavolisib tablet orally (PO) along with fulvestrant as an intramuscular (IM) injection.	Drug: Inavolisib; Participants will receive Inavolisib as per the schedule given in the protocol.; Drug: Fulvestrant; Participants will receive Fulvestrant as per the schedule given in the protocol.
Experimental: Inavolisib Dose B plus Fulvestrant; Participants will recieve an inavolisib tablet PO along with fulvestrant as an IM injection.	Drug: Inavolisib; Participants will receive Inavolisib as per the schedule given in the protocol.; Drug: Fulvestrant; Participants will receive Fulvestrant as per the schedule given in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Objective Response Rate (ORR)	Up to approximately 2 years
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Up to approximately 2 years
Progression-free Survival (PFS)	Up to approximately 2 years
Time to Response (TTR)	Up to approximately 2 years
Percentage of Participants With Treatment Discontinuation due to Adverse Events	Up to approximately 2 years
Number of Participants Reporting Presence, Frequency, Severity and/or Degree of Interference With Daily Activities of Symptomatic Treatment Toxicities as Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Up to approximately 2 years
Percentage of Participants Reporting Presence and Frequency of Selected Hyperglycemia Symptoms as Assessed by European Organisation for Research and Treatment of Cancer (EORTC) IL382	Up to approximately 2 years
Percentage of Participants Reporting Each Response Option at Each Time Point for the Treatment Side-Effect Bother Item General Population, Question 5 (GP5) From the Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire	Up to approximately 2 years
Change from Baseline in Symptomatic Treatment-Related Toxicities as Assessed Through use of the PRO-CTCAE	Baseline, Up to approximately 2 years
Change from Baseline in Selected Hyperglycemia Symptoms as Assessed by EORTC IL382	Baseline, Up to approximately 2 years
Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item	Baseline, Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2026
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): October 31, 2031

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: January 23, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; inavolisib
• Other Study ID Numbers: WO46063; 2025-522805-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No