A Study Evaluating Single-agent Inavolisib, Inavolisib Plus Atezolizumab, and Inavolisib Plus Pembrolizumab in PIK3CA-Mutated Cancers

NCT06496568 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CO439092021-006618-36
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 8

Brief Summary

The purpose of the study is to assess the safety and efficacy of inavolisib as a single-agent, in combination with atezolizumab, and in combination with pembrolizumab in participants with phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)-mutated cancers, including previously treated head and neck squamous cell carcinoma (HNSCC).

Conditions

PIK3CA-Mutated Cancers

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Select Treatment-related Toxicities (TRT) in Arm B and Arm C

  Day 1 of Cycle 1 to Day 3 of Cycle 2 (each cycle = 21 days)

• Percentage of Participants with Adverse Events (AEs) and serious adverse events (SAEs)

  From baseline up to approximately 3 years

Secondary Outcomes (17)

• Objective Response Rate (ORR)

  Every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (up to approximately 3 years)

• Best Objective Response (BOR)

  Every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (up to approximately 3 years)

• Duration of Response (DOR)

  Every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (up to approximately 3 years)

• Clinical Benefit Rate (CBR)

  Every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (up to approximately 3 years)

• Progression-free Survival (PFS)

  Every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (up to approximately 3 years)

Study Arms (3)

Arm A

EXPERIMENTAL

Participants in this group will receive inavolisib tablets, to be taken by mouth (PO), once daily (QD), on Days 1-21 of each cycle.

Drug: Inavolisib

Arm B

EXPERIMENTAL

Participants in this group will receive inavolisib tablets, to be taken PO, QD and atezolizumab given as an intravenous (IV) infusion once every 3 weeks (Q3W).

Drug: Inavolisib; Drug: Atezolizumab

Arm C

EXPERIMENTAL

Participants in this group will receive inavolisib tablets taken PO, QD and pembrolizumab administered as an IV infusion Q3W.

Drug: Inavolisib; Drug: Pembrolizumab

Interventions

Inavolisib DRUG

Participants will receive inavolisib, 9 milligram (mg), PO, QD on Days 1-21 of each 21-day cycle.

Arm A; Arm B; Arm C

Atezolizumab DRUG

Participants will receive atezolizumab, 1200 mg, as IV infusion Q3W on Day 1 of each 21-day cycle.

Arm B

Pembrolizumab DRUG

Participants will receive pembrolizumab as an IV infusion Q3W on Day 1 of each 21-day cycle.

Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed recurrent and/or metastatic HNSCC that has been previously treated with systemic therapy in the recurrent and/or metastatic setting
• Documented positive or negative human papillomavirus (HPV) status as determined locally by p16 immunohistochemistry (IHC; preferred), in situ hybridization, and/or by polymerase chain reaction-based assay
• Eligible participants must not be suitable for treatment with surgery and/or radiation
• Confirmation of biomarker eligibility: Valid results from either central testing of blood or previously conducted local testing of blood or tumour tissue documenting PIK3CA-mutated tumour status
• Consent to provide fresh (preferred) or archival tumour tissue specimen
• Negative hepatitis B surface antigen (HBsAg) and total hepatitis B core antibody (HBcAb) test or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• Adequate cardiovascular function
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of \>=12 weeks

You may not qualify if:

• Prior treatment with any phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathway
• Appropriate for treatment with surgery and/or radiation at the time of entry into the study, as per national or local treatment guidelines
• Type II diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type I diabetes
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible provided they meet specified criteria
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures twice per week or more frequently
• Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of the need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
• Uncontrolled tumor-related pain
• Any concurrent ocular or intraocular condition excluding cataracts (e.g., diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
• Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
• Requirement for daily supplemental oxygen
• Symptomatic active lung disease, including pneumonitis
• History of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis)
• Known Human Immunodeficiency Virus (HIV) infection

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Moores Cancer Center at UC San Diego Health

La Jolla, California, 92093, United States

WITHDRAWN

California Cancer Associates for Research & Excellence, Inc.

San Marcos, California, 92069, United States

WITHDRAWN

Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, 37232, United States

RECRUITING

BC Cancer Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

WITHDRAWN

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Interventions

inavolisib; atezolizumab; pembrolizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: CO43909 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: July 11, 2024
• Study Start: December 11, 2023
• Primary Completion (Estimated): September 28, 2028
• Study Completion (Estimated): September 28, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); KR (2); US (3)