ZN-c3 in Adult Participants with Metastatic Colorectal Cancer

Phase 1
Active, not recruiting
Conditions
Interventions
Registration Number
NCT05743036
Lead Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
82
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose EscalationZN-c3Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Dose EscalationEncorafenibParticipants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Dose EscalationCetuximabParticipants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Dose ExpansionZN-c3Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Dose ExpansionEncorafenibParticipants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Dose ExpansionCetuximabParticipants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Primary Outcome Measures
NameTimeMethod
Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)From Lead-in Day -1 to Cycle 1 Day 28

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.

Dose Expansion Phase - Objective response rate (ORR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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.

Secondary Outcome Measures
NameTimeMethod
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) v5.0From first dose of any study intervention through 28 days after the last dose of any study intervention

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

Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: CmaxCycle 1 Day 15
Proportion of participants with dose interruptions due to AEs in Dose Escalation PhaseFrom 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 PhaseFrom 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 PhaseFrom 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

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.

Dose Escalation Phase - Duration of Response (DOR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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.

Dose Escalation Phase - Progression Free Survival (PFS)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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.

Dose Escalation Phase - Disease Control Rate (DCR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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

Dose Escalation Phase - Time to Response (TTR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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

Dose Escalation - ZN-c3 plasma exposure: AUCFrom lead in day -1 visit through Cycle 1 Day 15
Dose Escalation - ZN-c3 plasma exposure: CmaxFrom lead in day -1 visit through Cycle 1 Day 15
Dose Escalation - ZN-c3 plasma exposure: TmaxFrom lead in day -1 visit through Cycle 1 Day 15
Dose Escalation - Encorafenib plasma exposure: AUCFrom lead in day -1 visit through Cycle 1 Day 15
Dose Escalation - Encorafenib plasma exposure: CmaxFrom lead in day -1 visit through Cycle 1 Day 15
Dose Escalation - Encorafenib plasma exposure: TmaxFrom lead in day -1 visit through Cycle 1 Day 15
Dose Expansion Phase - Duration of Response (DOR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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.

Dose Expansion Phase - Progression Free Survival (PFS)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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.

Dose Expansion Phase - Disease Control Rate (DCR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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

Dose Expansion Phase - Time to Response (TTR)From first dose of any study intervention every 8 weeks during treatment, up to 12 months

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

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) v5.0From first dose of any study intervention through 28 days after the last dose of any study intervention

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

Proportion of participants with dose interruptions due to AEs in Dose Expansion PhaseFrom 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 PhaseFrom 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 PhaseFrom 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: AUCLead in day 7
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: CmaxLead in day 7
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: TmaxDay 7
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUCCycle 1 Day 15
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: TmaxCycle 1 Day 15
Dose Expansion - ZN-c3 plasma exposure: AUCCycle 1 Day 15
Dose Expansion - ZN-c3 plasma exposure: CmaxCycle 1 Day 15
Tumor tissue BRAF V600E mutational statusFrom lead in day 1 visit through the last dose of any study intervention, up to 12 months

Trial Locations

Locations (27)

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, Bayern, Germany

Klinikum der Universität München Großhadern

🇩🇪

Muenchen, Bayern, Germany

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

🇩🇪

Muenchen, Bayern, Germany

Institut für Klinisch Onkologische Forschung

🇩🇪

Frankfurt, Hessen, Germany

DRK Kliniken Berlin - Köpenick

🇩🇪

Berlin, Germany

Semmelweis University-Department of Internal Medicine and Oncology

🇭🇺

Budapest, Hungary

Clinexpert Kft. Bugat Pal Korhaz

🇭🇺

Gyöngyös, Hungary

Istituto Nazionale Tumori IRCCS Fondazione Pascale

🇮🇹

Napoli, Campania, Italy

IRCCS Casa Sollievo della Sofferenza

🇮🇹

San Giovanni Rotondo, Foggia, Italy

AOUI Verona

🇮🇹

Verona, Veneto, Italy

Istituto Europeo di Oncologia

🇮🇹

Milano, Italy

ASST Grande Ospedale Metropolitano Niguarda

🇮🇹

Milano, Italy

Szpital Uniwersytecki w Krakowie

🇵🇱

Kraków, Malopolskie, Poland

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

🇵🇱

Kraków, Malopolskie, Poland

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

🇵🇱

Warsaw, Mazowieckie, Poland

Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego

🇵🇱

Opole, Opolskie, Poland

Parc de Salut Mar - Hospital del Mar

🇪🇸

Barcelona, Cataluna, Spain

Hospital Universitario Reina Sofia

🇪🇸

Córdoba, Cordoba, Spain

Fundación Instituto Valenciano de Oncología

🇪🇸

Valencia, Valenciana, Comunitat, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Puerta de Hierro Majadahonda

🇪🇸

Madrid, Spain

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