ZN-c3 in Adult Participants with Metastatic Colorectal Cancer
- Conditions
- Interventions
- Registration Number
- NCT05743036
- 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation ZN-c3 Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab Dose Escalation Encorafenib Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab Dose Escalation Cetuximab Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab Dose Expansion ZN-c3 Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab Dose Expansion Encorafenib Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab Dose Expansion Cetuximab Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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: Cmax Cycle 1 Day 15 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 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: AUC From lead in day -1 visit through Cycle 1 Day 15 Dose Escalation - ZN-c3 plasma exposure: Cmax From lead in day -1 visit through Cycle 1 Day 15 Dose Escalation - ZN-c3 plasma exposure: Tmax From lead in day -1 visit through Cycle 1 Day 15 Dose Escalation - Encorafenib plasma exposure: AUC From lead in day -1 visit through Cycle 1 Day 15 Dose Escalation - Encorafenib plasma exposure: Cmax From lead in day -1 visit through Cycle 1 Day 15 Dose Escalation - Encorafenib plasma exposure: Tmax From 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) v5.0 From 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 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 Expansion 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 Expansion Phase 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 Lead in day 7 Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax Lead in day 7 Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax Day 7 Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC Cycle 1 Day 15 Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax Cycle 1 Day 15 Dose Expansion - ZN-c3 plasma exposure: AUC Cycle 1 Day 15 Dose Expansion - ZN-c3 plasma exposure: Cmax Cycle 1 Day 15 Tumor tissue BRAF V600E mutational status From 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