ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

Phase 1TerminatedNCT05743036

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc44 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Colorectal Cancer

Interventions

ZN-c3DRUG

ZN-c3 tablet by mouth, in combination with encorafenib

EncorafenibDRUG

Encorafenib capsule by mouth, in combination with ZN-c3

CetuximabDRUG

Infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (27)

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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

Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.

Time frame: 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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Alliance for Multispecialty Research, LLC

Merriam, Kansas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Hämatologie- Onkologie im Zentrum MVZ GmbH

Augsburg, Bavaria, Germany

Klinikum der Universität München Großhadern

Munich, Bavaria, Germany

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

Munich, Bavaria, Germany

Institut für Klinisch Onkologische Forschung

Frankfurt am Main, Hesse, Germany

DRK Kliniken Berlin - Köpenick

Berlin, State of Berlin, Germany

...and 17 more locations

Time frame: 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)

ORR defined as the proportion of participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST Version 1.1.

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

Dose Escalation Phase - Duration of Response (DOR)

DOR defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause.

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

Dose Escalation Phase - Progression Free Survival (PFS)

PFS defined as the time from the first dose to the earliest documented disease progression per RECIST version 1.1, or death due to any cause.

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

Dose Escalation Phase - Disease Control Rate (DCR)

DCR defined as the proportion of participants with BOR of CR, PR, or stable disease (SD), per RECIST version 1.1.

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

Dose Escalation Phase - Time to Response (TTR)

TTR defined as the time from first dose to first radiographic evidence of response (CR or PR) per RECIST version 1.1.

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

Dose Escalation - ZN-c3 plasma exposure: AUC

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Escalation - ZN-c3 plasma exposure: Cmax

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Escalation - ZN-c3 plasma exposure: Tmax

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Escalation - Encorafenib plasma exposure: AUC

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Escalation - Encorafenib plasma exposure: Cmax

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Escalation - Encorafenib plasma exposure: Tmax

Time frame: From lead in day -1 visit through Cycle 1 Day 15

Dose Expansion Phase - Duration of Response (DOR)

DOR defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause.

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

Dose Expansion Phase - Progression Free Survival (PFS)

PFS defined as the time from the first dose to the earliest documented disease progression per RECIST version 1.1, or death due to any cause.

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

Dose Expansion Phase - Disease Control Rate (DCR)

DCR defined as the proportion of participants with BOR of CR, PR, or stable disease (SD), per RECIST version 1.1.

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

Dose Expansion Phase - Time to Response (TTR)

TTR defined as the time from first dose to first radiographic evidence of response (CR or PR) per RECIST version 1.1.

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

Dose Expansion 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

Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.

Time frame: 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 Expansion Phase

Time frame: 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 Expansion Phase

Time frame: 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 Expansion Phase

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

Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC

Time frame: Lead in day 7

Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax

Time frame: Lead in day 7

Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax

Time frame: Day 7

Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC

Time frame: Cycle 1 Day 15

Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax

Time frame: Cycle 1 Day 15

Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax

Time frame: Cycle 1 Day 15

Dose Expansion - ZN-c3 plasma exposure: AUC

Time frame: Cycle 1 Day 15

Dose Expansion - ZN-c3 plasma exposure: Cmax

Time frame: Cycle 1 Day 15

Tumor tissue BRAF V600E mutational status

Time frame: From lead in day 1 visit through the last dose of any study intervention, up to 12 months