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

NCT04495621 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MEN1611-022019-003727-38
• Study Type: interventional
• Target: 29
• Locations: 7 countries
• Sites: 28

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; PI3K Inhibitor; PIK3CA mutated; MEN1611; Cetuximab; anti-EGFR; mCRC

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab

  RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.

  Day 1 through Day 28 of Cycle 1 (28 days/cycle)

• Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab

  The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).

  Up to 37 Months

• Phase 1b: Number of Participants With DLTs for MEN1611

  A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting \>7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.

  Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Secondary Outcomes (5)

• Plasma Concentration of MEN1611 in Combination With Cetuximab

  Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)

• Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab

  Up to 37 Months

• Duration of Response (DOR) of MEN1611 in Combination With Cetuximab

  Up to 37 months

• Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab

  Up to 37 months

• Overall Survival (OS) of MEN1611 in Combination With Cetuximab

  Up to 37 months

Study Arms (1)

MEN1611

EXPERIMENTAL

MEN1611 + Cetuximab

Drug: MEN1611; Drug: Cetuximab

Interventions

MEN1611 DRUG

MEN1611 oral dose administered twice daily for a continuous 28-day cycle.

MEN1611

Cetuximab DRUG

Cetuximab solution for infusion administered weekly via intravenous infusion.

MEN1611

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (28)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

The Oncology Institute of Hope and Innovation

Anaheim, California, 92801, United States

Location

MultiCare Health System Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

ICO - Site Paul Papin

Angers, 49055, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

ICO - Site René Gauducheau

Saint-Herblain, 44800, France

Location

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Klinikum der Universitaet Muenchen Campus Grosshadern

Munich, 81377, Germany

Location

Klinikum rechts der Isar der TU

Munich, 81675, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Azienda Ospedaliero Universitaria San Martino

Genoa, 16132, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, 20141, Italy

Location

Azienda Socio Sanitaria Territoriale Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Amsterdam University Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Radboud Nijmegen

Nijmegen, 6525 GA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Examen sp. z o.o.

Skórzewo, 60-185, Poland

Location

Centrum Onkologii-Instytut im.M.Sklodowskiej Curie

Warsaw, 00-001, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

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

Results Point of Contact

• Title: Clinical Sciences
• Organization: Menarini Ricerche S.p.A.

martine.piccart@bordet.be

+39 0555680

Study Officials

• Josep Tabernero, MD, PhD

  Vall d' Hebron Institute of Oncology (VHIO), Barcelona, Spain

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: August 3, 2020
• Study Start: July 20, 2020
• Primary Completion: January 12, 2024
• Study Completion: February 27, 2024
• Last Updated: May 1, 2025
• Results First Posted: May 1, 2025

Record last verified: 2025-04

Locations

DE (6); PL (2); NL (4); US (3); IT (5); ES (5); FR (3)