A Study to Evaluate the Efficacy and Safety of Inavolisib When Administered in Combination With Bevacizumab and FOLFOX or FOLFIRI as First Line Therapy in Participants With Colorectal Cancer (INAVO-CRC)

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib With Bevacizumab Plus Folfox or Folfiri as First Line Therapy in Patients With PIK3CA-Mutated Metastatic Colorectal Cancer

This is a blinded Phase 2 study designed to evaluate the safety and efficacy of inavolisib with bevacizumab and chemotherapy, in participants with metastatic colorectal cancer (mCRC) whose tumors have a PIK3CA mutation. The study has a safety run-in period followed by a randomized period.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Inavolisib; Drug: Bevacizumab; Drug: FOLFOX; Drug: FOLFIRI; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) <=1
• Histologically confirmed adenocarcinoma originating in the colon or rectum of the Stage 4 ( treatment plan does not include resection or curative ablation) per American Joint Committee on Cancer (AJCC) v8
• Measurable disease per RECIST v1.1
• No prior systemic therapy in the metastatic setting
• Confirmation of biomarker eligibility: documentation of a PIK3CA mutation from either central testing of tissue, or from a validated historically obtained (pre-existing) test of tumor tissue or blood may be used to confirm eligibility
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment
• Agreement to adhere to the contraception requirements

Exclusion Criteria:

• Biomarker eligibility as per definition
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry or any history of Type 1 diabetes
• Residual Grade 2 or higher neuropathy due to prior oxaliplatin exposure (unless the participant is planned to be treated with FOLFIRI)
• Symptomatic, untreated, or actively progressing CNS metastases
• History of gastrointestinal (GI) fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 1 of Cycle 1
• Treatment with strong cytochrome P450 (CYP) 3A4 inducers or strong CYP3A4 inhibitors within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment (only for patients who will receive FOLFIRI)
• Known HIV positive status with exceptions for well controlled and on stable treatment
• History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.	Drug: Inavolisib; Participants will receive Inavolisib as per the schedule mentioned in the protocol.; Other Names: GDC-0077; Itovebi; Drug: Bevacizumab; Participants will receive Bevacizumab as per the schedule mentioned in the protocol.; Other Names: Avastin; Drug: FOLFOX; Participants will receive FOLFOX as per the schedule mentioned in the protocol.; Drug: FOLFIRI; Participants will receive FOLFIRI as per the schedule mentioned in the protocol.
Placebo Comparator: Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo; Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.	Drug: Bevacizumab; Participants will receive Bevacizumab as per the schedule mentioned in the protocol.; Other Names: Avastin; Drug: FOLFOX; Participants will receive FOLFOX as per the schedule mentioned in the protocol.; Drug: FOLFIRI; Participants will receive FOLFIRI as per the schedule mentioned in the protocol.; Drug: Placebo; Participants will receive Placebo as per the schedule mentioned in the protocol.
Experimental: Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.	Drug: Inavolisib; Participants will receive Inavolisib as per the schedule mentioned in the protocol.; Other Names: GDC-0077; Itovebi; Drug: Bevacizumab; Participants will receive Bevacizumab as per the schedule mentioned in the protocol.; Other Names: Avastin; Drug: FOLFOX; Participants will receive FOLFOX as per the schedule mentioned in the protocol.; Drug: FOLFIRI; Participants will receive FOLFIRI as per the schedule mentioned in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-in Period: Percentage of Participants With Adverse Events (AEs)		Approximately 4 Years
Percentage of Participants With an Objective Response Rate	The percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1.)	From Baseline Untill Radiographic Disease Progression (Approximately 4 Years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Time from randomization to death from any cause or the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 (whichever occurs first)	From Baseline Untill Radiographic Disease Progression (up to Approximately 4 Years)
Randomized Phase: Overall Survival (OS)	Defined as the time from randomization to death from any cause	From Baseline Untill Death (up to Approximately 4 Years)
Randomized Phase: Disease Control Rate (DCR)	Defined as the percentage of participants with stable disease for >=12 weeks or a CR or PR as determined by the investigator according to RECIST v1.1	From Baseline Untill Disease Progression (up to Approximately 4 Years)
Randomized Phase: Duration of Response (DOR)	Defined as the time from the first occurrence of a documented confirmed OR to death from any cause or the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, (whichever occurs first)	From Baseline Untill Disease Progression or Death (up to Approximately 4 Years)
Randomized Phase: Percentage of Participants With AEs		From Baseline up to 90 Days After the Final Dose of study treatment or Until Initiation of Another Anti-cancer Therapy (up to Approximately 4 Years)
Percentage of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)		Up to Approximately 4 Years
Percentage of Participants Troubled by Treatment Symptoms, as Assessed by Single Item European Organisation for Research and Treatment of Cancer Item Library 46 (EORTC IL46)		Up to Approximately 4 Years
Change From Baseline in Symptomatic Treatment Toxicities as Assessed by PRO-CTCAE		Baseline up to Approximately 4 Years
Change From Baseline in Treatment Side-effect Bother as Assessed by EORTC IL46 item		Baseline up to Approximately 4 Years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Actual): January 7, 2026

Study Record Updates

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

More Information

Terms related to this study

• Keywords: PIK3CA-mutated Colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; inavolisib; Folfox protocol; IFL protocol
• Other Study ID Numbers: WO46300; 2025-523014-84-00 (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