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

Menarini

Status and phase

Completed

Phase 2

Phase 1

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Cetuximab

Drug: MEN1611

Study type

Interventional

Funder types

Industry

Identifiers

NCT04495621

MEN1611-02

2019-003727-38 (EudraCT Number)

Details and patient eligibility

About

Open-label, dose-confirmation and cohort expansion, multicenter, Phase Ib/II study to assess the anti-tumor activity and safety of MEN1611 in combination with cetuximab for the treatment of participants with phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA)-mutated metastatic colorectal cancer.

Full description

This Phase Ib/II study investigated the anti-tumor activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male participants affected by PIK3CA-mutated, neuroblastoma-Kristen-rat sarcoma virus (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 of MEN1611 given as single agent was assessed in a Phase I trial in participants with advanced solid tumors.

This Phase Ib/II started with a dose confirmation part (Step 1) to identify the recommended phase 2 dose of MEN1611 given in combination with cetuximab.

The study continued with a cohort expansion (Step 2) to explore the anti-tumor activity of the selected MEN1611 dose level combined with cetuximab with further assessment of safety and tolerability.

Enrollment

29 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Main Inclusion Criteria:

Histological documentation of adenocarcinoma of the colon or rectum.
Progression or recurrence following prior irinotecan, oxaliplatin, 5-fluorouracil (5-FU) and anti-epidermal growth factor receptor (EGFR) containing regimens for metastatic disease.
Best response according to Response Evaluation Criteria in Solid Tumours (RECIST) 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 performance status 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.
National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Grade ≥2 diarrhea.
History of significant, uncontrolled or active cardiovascular disease.
Known active or uncontrolled pulmonary dysfunction.
Uncontrolled diabetes mellitus (glycated hemoglobin >7%) and fasting plasma glucose >126 milligrams/deciliter.
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.