Back to resultsZN-c3 in Adult Participants With Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ZN-c3
Encorafenib
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer, CRC, BRAF V600E
Eligibility 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
Sites / Locations
- Alliance for Multispecialty Research, LLCRecruiting
- University of Texas MD Anderson Cancer CenterRecruiting
- The Queen Elizabeth HospitalRecruiting
- Peter MacCallum Cancer CentreRecruiting
- Hämatologie- Onkologie im Zentrum MVZ GmbHRecruiting
- DRK Kliniken Berlin - KöpenickRecruiting
- Semmelweis University-Department of Internal Medicine and OncologyRecruiting
- Clinexpert Kft. Bugat Pal KorhazRecruiting
- Istituto Nazionale Tumori IRCCS Fondazione PascaleRecruiting
- IRCCS Casa Sollievo della SofferenzaRecruiting
- AOUI VeronaRecruiting
- Istituto Europeo di OncologiaRecruiting
- ASST Grande Ospedale Metropolitano NiguardaRecruiting
- Szpital Specjalistyczny im. Ludwika Rydygiera w KrakowieRecruiting
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w WarszawieRecruiting
- Parc de Salut Mar - Hospital del MarRecruiting
- Hospital Universitario Reina SofiaRecruiting
- Fundación Instituto Valenciano de OncologíaRecruiting
- Hospital Universitario La PazRecruiting
- Hospital Universitario Puerta de Hierro MajadahondaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose Escalation
Dose Expansion
Arm Description
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase
Proportion of participants with dose modifications due to AEs in Dose Escalation Phase
Proportion of participants with discontinuations due to AEs in Dose Escalation Phase
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.
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.
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.
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.
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.
Dose Escalation - ZN-c3 plasma exposure: AUC
Dose Escalation - ZN-c3 plasma exposure: Cmax
Dose Escalation - ZN-c3 plasma exposure: Tmax
Dose Escalation - Encorafenib plasma exposure: AUC
Dose Escalation - Encorafenib plasma exposure: Cmax
Dose Escalation - Encorafenib plasma exposure: Tmax
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.
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.
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.
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.
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.
Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase
Proportion of participants with dose modifications due to AEs in Dose Expansion Phase
Proportion of participants with discontinuations due to AEs in Dose Expansion Phase
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax
Dose Expansion - ZN-c3 plasma exposure: AUC
Dose Expansion - ZN-c3 plasma exposure: Cmax
Tumor tissue BRAF V600E mutational status
Full Information
NCT ID
NCT05743036
First Posted
January 26, 2023
Last Updated
October 24, 2023
Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT05743036
Brief Title
ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 27, 2023 (Actual)
Primary Completion Date
August 21, 2026 (Anticipated)
Study Completion Date
September 25, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Collaborators
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic Colorectal Cancer, CRC, BRAF V600E
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Arm Title
Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Intervention Type
Drug
Intervention Name(s)
ZN-c3
Intervention Description
ZN-c3 tablet by mouth, in combination with encorafenib
Intervention Type
Drug
Intervention Name(s)
Encorafenib
Other Intervention Name(s)
BRAFTOVI®
Intervention Description
Encorafenib capsule by mouth, in combination with ZN-c3
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
ERBITUX®
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)
Description
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
Title
Dose Expansion Phase - Objective response rate (ORR)
Description
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 Outcome Measure Information:
Title
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
Description
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
Title
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
Title
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
Title
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
Title
Dose Escalation Phase - Objective response rate (ORR)
Description
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
Title
Dose Escalation Phase - Duration of Response (DOR)
Description
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
Title
Dose Escalation Phase - Progression Free Survival (PFS)
Description
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
Title
Dose Escalation Phase - Disease Control Rate (DCR)
Description
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
Title
Dose Escalation Phase - Time to Response (TTR)
Description
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
Title
Dose Escalation - ZN-c3 plasma exposure: AUC
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Escalation - ZN-c3 plasma exposure: Cmax
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Escalation - ZN-c3 plasma exposure: Tmax
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Escalation - Encorafenib plasma exposure: AUC
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Escalation - Encorafenib plasma exposure: Cmax
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Escalation - Encorafenib plasma exposure: Tmax
Time Frame
From lead in day -1 visit through Cycle 1 Day 15
Title
Dose Expansion Phase - Duration of Response (DOR)
Description
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
Title
Dose Expansion Phase - Progression Free Survival (PFS)
Description
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
Title
Dose Expansion Phase - Disease Control Rate (DCR)
Description
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
Title
Dose Expansion Phase - Time to Response (TTR)
Description
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
Title
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
Description
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
Title
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
Title
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
Title
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
Title
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC
Time Frame
Lead in day 7
Title
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax
Time Frame
Lead in day 7
Title
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax
Time Frame
Day 7
Title
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC
Time Frame
Cycle 1 Day 15
Title
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax
Time Frame
Cycle 1 Day 15
Title
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax
Time Frame
Cycle 1 Day 15
Title
Dose Expansion - ZN-c3 plasma exposure: AUC
Time Frame
Cycle 1 Day 15
Title
Dose Expansion - ZN-c3 plasma exposure: Cmax
Time Frame
Cycle 1 Day 15
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals
Phone
(212) 433-3791
Email
info@zenopharma.com
Facility Information:
Facility Name
Alliance for Multispecialty Research, LLC
City
Merriam
State/Province
Kansas
ZIP/Postal Code
66204
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
The Queen Elizabeth Hospital
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Hämatologie- Onkologie im Zentrum MVZ GmbH
City
Augsburg
State/Province
Bayern
ZIP/Postal Code
86150
Country
Germany
Individual Site Status
Recruiting
Facility Name
DRK Kliniken Berlin - Köpenick
City
Berlin
ZIP/Postal Code
12559
Country
Germany
Individual Site Status
Recruiting
Facility Name
Semmelweis University-Department of Internal Medicine and Oncology
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Clinexpert Kft. Bugat Pal Korhaz
City
Gyöngyös
ZIP/Postal Code
3200
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Istituto Nazionale Tumori IRCCS Fondazione Pascale
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Casa Sollievo della Sofferenza
City
San Giovanni Rotondo
State/Province
Foggia
ZIP/Postal Code
71013
Country
Italy
Individual Site Status
Recruiting
Facility Name
AOUI Verona
City
Verona
State/Province
Veneto
ZIP/Postal Code
37126
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Europeo di Oncologia
City
Milano
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Recruiting
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
ZIP/Postal Code
20162
Country
Italy
Individual Site Status
Recruiting
Facility Name
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
City
Kraków
State/Province
Malopolskie
ZIP/Postal Code
31-826
Country
Poland
Individual Site Status
Recruiting
Facility Name
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
City
Warsaw
State/Province
Mazowieckie
ZIP/Postal Code
02-034
Country
Poland
Individual Site Status
Recruiting
Facility Name
Parc de Salut Mar - Hospital del Mar
City
Barcelona
State/Province
Cataluna
ZIP/Postal Code
08003
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Reina Sofia
City
Córdoba
State/Province
Cordoba
ZIP/Postal Code
14004
Country
Spain
Individual Site Status
Recruiting
Facility Name
Fundación Instituto Valenciano de Oncología
City
Valencia
State/Province
Valenciana, Comunitat
ZIP/Postal Code
46009
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Puerta de Hierro Majadahonda
City
Madrid
ZIP/Postal Code
28222
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
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