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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 10, 2023
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: ZN-c3 Drug: Encorafenib Drug: Cetuximab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 27, 2023
Estimated Primary Completion Date : August 21, 2026
Estimated Study Completion Date : September 25, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
 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®
Experimental: Dose Expansion
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
 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®


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Dose Escalation - ZN-c3 plasma exposure: AUC [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  11. Dose Escalation - ZN-c3 plasma exposure: Cmax [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  12. Dose Escalation - ZN-c3 plasma exposure: Tmax [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  13. Dose Escalation - Encorafenib plasma exposure: AUC [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  14. Dose Escalation - Encorafenib plasma exposure: Cmax [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  15. Dose Escalation - Encorafenib plasma exposure: Tmax [ Time Frame: From lead in day -1 visit through Cycle 1 Day 15 ]
  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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 ]
  22. 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 ]
  23. 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 ]
  24. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC [ Time Frame: Lead in day 7 ]
  25. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax [ Time Frame: Lead in day 7 ]
  26. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax [ Time Frame: Day 7 ]
  27. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC [ Time Frame: Cycle 1 Day 15 ]
  28. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax [ Time Frame: Cycle 1 Day 15 ]
  29. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax [ Time Frame: Cycle 1 Day 15 ]
  30. Dose Expansion - ZN-c3 plasma exposure: AUC [ Time Frame: Cycle 1 Day 15 ]
  31. Dose Expansion - ZN-c3 plasma exposure: Cmax [ Time Frame: Cycle 1 Day 15 ]
  32. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05743036


Contacts
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Contact: K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals (212) 433-3791 info@zenopharma.com

Locations
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United States, Kansas
Alliance for Multispecialty Research, LLC Recruiting
Merriam, Kansas, United States, 66204
Sponsors and Collaborators
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Pfizer
More Information
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Responsible Party: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT05743036    
Other Study ID Numbers: ZN-c3-016
Z0011001 ( Other Identifier: Pfizer )
First Posted: February 24, 2023    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc:
Metastatic Colorectal Cancer
CRC
BRAF V600E
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents