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

A Phase I/Ib Study Evaluating Single-Agent Inavolisib, Inavolisib Plus Atezolizumab in PIK3CA-Mutated Cancers

The purpose of the study is to assess the safety and efficacy of inavolisib as a single-agent and in combination with atezolizumab 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).

Study Overview

• Status: Active, not recruiting
• Conditions: PIK3CA-Mutated Cancers
• Intervention / Treatment: Drug: Inavolisib; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Vancouver Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Ctr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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 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
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of >=12 weeks

Exclusion Criteria:

• 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
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, metabolic, or infectious disease) or any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that renders the participant at high risk from treatment complications
• Chemotherapy, radiotherapy, or any other anti-cancer therapy within 2 weeks before enrolment
• Investigational drug(s) within 4 weeks before enrolment
• Unresolved toxicity from prior therapy, except for hot flashes, alopecia, and Grade <=2 peripheral neuropathy
• History of other malignancy within 5 years prior to screening, with specified exceptions
• History of or active clinically significant cardiovascular dysfunction
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study)
• Chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• Allergy or hypersensitivity to components of the inavolisib, atezolizumab, or pembrolizumab formulation
• Treatment with strong CYP3A4 inducers or strong CYP3A4 inhibitors within 1 week or five drug-elimination half-lives, whichever is longer, prior to initiation of study treatment
• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1; or anticipation of the need for major surgery during study treatment
• Minor surgical procedures <7 days prior to the first dose of study treatment

Exclusion criteria specific to arms utilizing atezolizumab:

• Prior serious immune-mediated toxicities resulting from treatment with any checkpoint inhibitor including, but not limited to, atezolizumab, pembrolizumab, or nivolumab
• Treatment with any checkpoint inhibitor within 5 half-lives of Day 1 of Cycle 1
• Uncontrolled or symptomatic hypercalcemia
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with specified exceptions
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; a history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteraemia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; participants receiving prophylactic antibiotics may be eligible for the study
• Prior allogeneic stem cell or solid organ transplantation
• Current treatment with anti-viral therapy for HBV
• Treatment with systemic immunostimulatory agents within 4 weeks or five drug-elimination half-lives of the drug (whichever is longer)
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with specified exceptions
• Poor peripheral venous access that would preclude repeated IV infusions
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; Participants will receive inavolisib, 9 milligram (mg), PO, QD on Days 1-21 of each 21-day cycle.
Experimental: Arm B; 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; Participants will receive inavolisib, 9 milligram (mg), PO, QD on Days 1-21 of each 21-day cycle.; Drug: Atezolizumab; Participants will receive atezolizumab, 1200 mg, as IV infusion Q3W on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Select Treatment-related Toxicities (TRT) in Arm B	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 Outcome Measures

Outcome Measure	Time Frame
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)
Plasma Concentration of Inavolisib in Arm A	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at predose on Day 1 of Cycle 3 (each cycle = 21 days)
Area Under the Concentration-time Curve (AUC) of Inavolisib in Arm A	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at predose on Day 1 of Cycle 3 (each cycle = 21 days)
Maximum Plasma Concentration (Cmax) of Inavolisib in Arm A	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at predose on Day 1 of Cycle 3 (each cycle = 21 days)
Minimum Plasma Concentration (Cmin) of Inavolisib in Arm A	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at predose on Day 1 of Cycle 3 (each cycle = 21 days)
Plasma Concentration of Inavolisib in Arm B	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and Predose on Day 1 of Cycle 3 (each cycle = 21 days)
AUC of Inavolisib in Arm B	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and Predose on Day 1 of Cycle 3 (each cycle = 21 days)
Cmax of Inavolisib in Arm B	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and Predose on Day 1 of Cycle 3 (each cycle = 21 days)
Cmin of Inavolisib in Arm B	Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and Predose on Day 1 of Cycle 3 (each cycle = 21 days)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): July 21, 2027
• Study Completion (Estimated): July 21, 2027

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 4, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Phosphoinositide-3 Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; atezolizumab; inavolisib
• Other Study ID Numbers: CO43909; 2021-006618-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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