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)

Roche

Status and phase: Not yet enrolling; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: FOLFIRI; Drug: Inavolisib; Drug: Bevacizumab; Drug: Placebo; Drug: FOLFOX

Study type: Interventional

Funder types: Industry

Identifiers

NCT07323576

2025-523014-84-00 (EU Trial (CTIS) Number)

WO46300

Details and patient eligibility

About

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.

Enrollment: 164 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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164 participants in 3 patient groups, including a placebo group

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib

Experimental group

Description:

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

Treatment:

Drug: FOLFOX

Drug: Bevacizumab

Drug: Inavolisib

Drug: FOLFIRI

Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: FOLFOX

Drug: Bevacizumab

Drug: FOLFIRI

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

Experimental group

Description:

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

Treatment:

Drug: FOLFOX

Drug: Bevacizumab

Drug: Inavolisib

Drug: FOLFIRI