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

NCT07323576 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: WO463002025-523014-84-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

PIK3CA-mutated Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Progression-free Survival (PFS)

  From Baseline Untill Radiographic Disease Progression (up to Approximately 4 Years)

• Randomized Phase: Overall Survival (OS)

  From Baseline Untill Death (up to Approximately 4 Years)

• Randomized Phase: Disease Control Rate (DCR)

  From Baseline Untill Disease Progression (up to Approximately 4 Years)

• Randomized Phase: Duration of Response (DOR)

  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)

Study Arms (3)

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

EXPERIMENTAL

Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.

Drug: Inavolisib; Drug: Bevacizumab; Drug: FOLFOX; Drug: FOLFIRI

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo

PLACEBO COMPARATOR

Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.

Drug: Bevacizumab; Drug: FOLFOX; Drug: FOLFIRI; Drug: Placebo

Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

EXPERIMENTAL

Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.

Drug: Inavolisib; Drug: Bevacizumab; Drug: FOLFOX; Drug: FOLFIRI

Interventions

Inavolisib DRUG

Participants will receive Inavolisib as per the schedule mentioned in the protocol.

Also known as: Itovebi, GDC-0077

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

Bevacizumab DRUG

Participants will receive Bevacizumab as per the schedule mentioned in the protocol.

Also known as: Avastin

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo; Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

FOLFOX DRUG

Participants will receive FOLFOX as per the schedule mentioned in the protocol.

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo; Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

FOLFIRI DRUG

Participants will receive FOLFIRI as per the schedule mentioned in the protocol.

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib; Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo; Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

Placebo DRUG

Participants will receive Placebo as per the schedule mentioned in the protocol.

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

inavolisib; Bevacizumab; Folfox protocol; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 7, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 31, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share