ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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 Names:
Drug: Cetuximab
Infusion
Other Names:
|
| 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 Names:
Drug: Cetuximab
Infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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: Cmax [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]
Eligibility Criteria
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
Locations
No locations specified.Sponsors and Collaborators
- K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
- Pfizer
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZN-c3-016
- Z0011001