Clinical Trials/NCT06496568

NCT06496568

Recruiting

Phase 1

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

Hoffmann-La Roche15 sites in 3 countries30 target enrollmentDecember 11, 2023

ConditionsPIK3CA-Mutated Cancers

InterventionsInavolisib Pembrolizumab Atezolizumab

DrugsInavolisib Atezolizumab

Overview

Phase: Phase 1
Intervention: Inavolisib
Conditions: PIK3CA-Mutated Cancers
Sponsor: Hoffmann-La Roche
Enrollment: 30
Locations: 15
Primary Endpoint: Percentage of Participants with Adverse Events (AEs) and serious adverse events (SAEs)
Status: Recruiting
Last Updated: 16 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

December 11, 2023

End Date

September 28, 2028

Last Updated

16 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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 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

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

Arms & Interventions

Arm C

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

Intervention: Inavolisib

Arm C

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

Intervention: Pembrolizumab

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).

Intervention: Inavolisib

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.

Intervention: Inavolisib

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).

Intervention: Atezolizumab

Outcomes

Primary Outcomes

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

Time Frame: From baseline up to approximately 3 years

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

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

Secondary Outcomes

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))
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))
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))
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))
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))
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))
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))
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))
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))
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))
Cmax of Inavolisib in Arm C(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))
Plasma Concentration of Inavolisib in Arm C(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 C(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 C(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))