MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)

Study Overview
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Brief Summary
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Open-label, dose-confirmation and cohort expansion, multicentre, Phase Ib/II study to assess the anti-tumour activity and safety of MEN1611 in combination with cetuximab for the treatment of patients with PIK3CA mutated metastatic colorectal cancer.

Detailed Description
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This Phase Ib/II study will investigate the anti-tumour activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male patients affected by PIK3CA mutated, N-K-RAS wild-type and BRAF wild-type metastatic colorectal cancer. MEN1611 is a potent, selective Class I phosphoinositide 3-kinase (PI3K) inhibitor. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors. This Phase Ib/II will start with a dose confirmation part (Step 1) to identify the RP2D of MEN1611 given in combination with cetuximab. The study will continue with a cohort expansion (Step 2) to explore the anti-tumour activity of the selected MEN1611 dose level combined with cetuximab with further assessment of their safety and tolerability.

Official Title
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Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: MEN1611
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histological documentation of adenocarcinoma of the colon or rectum. Progression or recurrence following prior irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens for metastatic disease. Best response according to Response Evaluation Criteria in Solid Tumours criteria to the last anti-EGFR containing regimen of partial response or stable disease for at least 4 months. Measurable disease according to RECIST criteria. N-K-RAS (exons 2, 3 and 4) and BRAF wild-type and PIK3CA mutated. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Main Exclusion Criteria: Previous treatment with PI3K inhibitor. Brain metastases, unless treated > 4 weeks before Screening Visit and only if clinically stable and not receiving corticosteroids. NCI CTCAE v5.0 Grade ≥ 2 diarrhoea. History of significant, uncontrolled or active cardiovascular disease. Known active or uncontrolled pulmonary dysfunction. Uncontrolled diabetes mellitus (HbA1c > 7%) and fasting plasma glucose > 126 mg/dL. Known history of human immunodeficiency virus infection or active infection with hepatitis C virus or hepatitis B virus. Concurrent chronic immunosuppressive treatment either with steroids or other immunosuppressive agents.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEN1611<br>MEN1611 + Cetuximab | Drug: MEN1611<br>* MEN1611 oral dose administered twice daily for a continuous 28-day cycle.<br>Drug: Cetuximab<br>* Cetuximab solution for infusion administered weekly via IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of recommended phase II dose (RP2D) | Determination of the recommended phase II dose of MEN1611 when administered orally in combination with cetuximab to patients with PIK3CA mutated colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens. | 28 Days | 
| Best overall response rate (ORR) according to RECIST v.1.1 | Assessment of the anti-tumour activity of MEN1611 in combination with cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens. | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) | Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0. | 36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Colorectal Cancer, PI3K Inhibitor, PIK3CA mutated, MEN1611, Cetuximab, anti-EGFR, mCRC