ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
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| ClinicalTrials.gov Identifier: NCT05743036 |
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Recruitment Status :
Recruiting
First Posted : February 24, 2023
Last Update Posted : March 8, 2024
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Sponsor:
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Collaborator:
Pfizer
Information provided by (Responsible Party):
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
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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 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
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
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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® |
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Experimental: Dose Expansion
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
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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® |
Primary Outcome Measures :
- 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.
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 [ 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 ]
Information from the National Library of Medicine
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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
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
| Contact: K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals | (212) 433-3791 | info@zenopharma.com |
Locations
Show 27 study locations
Sponsors and Collaborators
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Pfizer
| 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 8, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| 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:
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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 |