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ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05743036
Recruitment Status : Recruiting
First Posted : February 24, 2023
Last Update Posted : March 8, 2024
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Tracking Information
First Submitted Date  ICMJE January 26, 2023
First Posted Date  ICMJE February 24, 2023
Last Update Posted Date March 8, 2024
Actual Study Start Date  ICMJE February 27, 2023
Estimated Primary Completion Date August 21, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2023)
  • Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2023)
  • 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 [ Time Frame: 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 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 [ 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
Official Title  ICMJE A Phase 1/2, Open-Label, Multi-Center Study of ZN-c3 Administered in Combination With Encorafenib and Cetuximab in Adults With Metastatic Colorectal Cancer
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: ZN-c3
    ZN-c3 tablet by mouth, in combination with encorafenib
  • Drug: Encorafenib
    Encorafenib capsule by mouth, in combination with ZN-c3
    Other Name: BRAFTOVI®
  • Drug: Cetuximab
    Infusion
    Other Name: ERBITUX®
Study Arms  ICMJE
  • Experimental: Dose Escalation
    Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
    Interventions:
    • Drug: ZN-c3
    • Drug: Encorafenib
    • Drug: Cetuximab
  • Experimental: Dose Expansion
    Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
    Interventions:
    • Drug: ZN-c3
    • Drug: Encorafenib
    • Drug: Cetuximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 15, 2023)		 82
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 25, 2026
Estimated Primary Completion Date August 21, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals (212) 433-3791 info@zenopharma.com
Listed Location Countries  ICMJE Australia,   Germany,   Hungary,   Italy,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05743036
Other Study ID Numbers  ICMJE ZN-c3-016
Z0011001 ( Other Identifier: Pfizer )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Pfizer
Investigators  ICMJE Not Provided
PRS Account K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP