ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

NCT05743036 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ZN-c3-016Z0011001
• Study Type: interventional
• Target: 44
• Locations: 7 countries
• Sites: 27

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and potential clinical benefits of ZN-c3 administered in combination with encorafenib and cetuximab in adult participants with metastatic BRAF V600E mutant colorectal cancer previously treated with one or two treatment regimens.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; CRC; BRAF V600E

Outcome Measures

Primary Outcomes (2)

• Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)

  DLTs defined as treatment-related AEs occurring within the first 29 days after the start of any study treatment that in the opinion of the investigator cannot be reasonably attributed to the participant's underlying disease, concomitant medications, or pre-existing conditions.

  From Lead-in Day -1 to Cycle 1 Day 28

• Dose Expansion Phase - Objective response rate (ORR)

  ORR defined as the proportion of participants who achieves a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator per RECIST Version 1.1.

  From first dose of any study intervention every 8 weeks during treatment, up to 12 months

Secondary Outcomes (32)

• Dose Escalation Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

  From first dose of any study intervention through 28 days after the last dose of any study intervention

• Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase

  From first dose of any study intervention through 28 days after the last dose of any study intervention

• Proportion of participants with dose modifications due to AEs in Dose Escalation Phase

  From first dose of any study intervention through 28 days after the last dose of any study intervention

• Proportion of participants with discontinuations due to AEs in Dose Escalation Phase

  From first dose of any study intervention through 28 days after the last dose of any study intervention

• Dose Escalation Phase - Objective response rate (ORR)

  From first dose of any study intervention every 8 weeks during treatment, up to 12 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab

Drug: ZN-c3; Drug: Encorafenib; Drug: Cetuximab

Dose Expansion

EXPERIMENTAL

Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab

Drug: ZN-c3; Drug: Encorafenib; Drug: Cetuximab

Interventions

ZN-c3 DRUG

ZN-c3 tablet by mouth, in combination with encorafenib

Dose Escalation; Dose Expansion

Encorafenib DRUG

Encorafenib capsule by mouth, in combination with ZN-c3

Also known as: BRAFTOVI®

Dose Escalation; Dose Expansion

Cetuximab DRUG

Infusion

Also known as: ERBITUX®

Dose Escalation; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed metastatic Stage IV colorectal adenocarcinoma.
• Documented evidence of a BRAF V600E mutation in tumor tissue or blood
• Presence of measurable disease per RECIST version 1.1 guidelines.
• Disease progression after 1 or 2 previous systemic regimens for metastatic disease
• Adequate bone marrow function
• Adequate hepatic and renal function

You may not qualify if:

• Documented clinical disease progression or radiographic disease progression during the screening period
• Leptomeningeal disease.
• Symptomatic brain metastasis.
• Presence of acute or chronic pancreatitis.
• Unable to swallow, retain, and absorb oral medications.
• Clinically significant cardiovascular diseases
• Evidence of active noninfectious pneumonitis.
• Evidence of active and uncontrolled bacterial or viral infection, within 2 weeks prior to start of any of the study interventions
• Participants with known positivity for HIV
• Active hepatitis B or hepatitis C infection
• Concurrent or previous other malignancy within 2 years of study entry
• Has had an allogeneic tissue/solid organ transplant
• Pregnant or females of childbearing potential who have a positive β-hCG laboratory test result within 14 days prior to enrollment or is breastfeeding

Sponsors & Collaborators

• K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc: lead
• Pfizer: collaborator

Study Sites (27)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Alliance for Multispecialty Research, LLC

Merriam, Kansas, 66204, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Hämatologie- Onkologie im Zentrum MVZ GmbH

Augsburg, Bavaria, 86150, Germany

Location

Klinikum der Universität München Großhadern

Munich, Bavaria, 81377, Germany

Location

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

Munich, Bavaria, 81737, Germany

Location

Institut für Klinisch Onkologische Forschung

Frankfurt am Main, Hesse, 60488, Germany

Location

DRK Kliniken Berlin - Köpenick

Berlin, State of Berlin, 12559, Germany

Location

Semmelweis University-Department of Internal Medicine and Oncology

Budapest, Budapest, 1083, Hungary

Location

Clinexpert Kft. Bugat Pal Korhaz

Gyöngyös, 3200, Hungary

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, Campania, 80131, Italy

Location

IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Istituto Europeo di Oncologia

Milan, Milano, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Milano, 20162, Italy

Location

AOUI Verona

Verona, Veneto, 37126, Italy

Location

Szpital Uniwersytecki w Krakowie

Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie

Warsaw, Masovian Voivodeship, 02-034, Poland

Location

Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego

Opole, Opole Voivodeship, 45-061, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Parc de Salut Mar - Hospital del Mar

Barcelona, Catalonia, 08003, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Madrid, 28222, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, Valenciana, Comunitat, 46009, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

encorafenib; 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

Study Design

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

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 24, 2023
• Study Start: February 27, 2023
• Primary Completion: July 16, 2024
• Study Completion: July 9, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); IT (5); PL (4); ES (6); US (3); AU (2); DE (5)