ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05743036
• Other study ID #: ZN-c3-016
• Secondary ID: Z0011001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 27, 2023
• Est. completion date: September 25, 2026

Study information

• Verified date: March 2024
• Source: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Contact: K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals
• Phone: (212) 433-3791
• Email: info[@]zenopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 82
• Est. completion date: September 25, 2026
• Est. primary completion date: August 21, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-hCG laboratory test result within 14 days prior to enrollment or is breastfeeding

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• ZN-c3
ZN-c3 tablet by mouth, in combination with encorafenib
• Encorafenib
Encorafenib capsule by mouth, in combination with ZN-c3
• Cetuximab
Infusion

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Germany	Hämatologie- Onkologie im Zentrum MVZ GmbH	Augsburg	Bayern
Germany	DRK Kliniken Berlin - Köpenick	Berlin
Germany	Institut für Klinisch Onkologische Forschung	Frankfurt	Hessen
Germany	Klinikum der Universität München Großhadern	Muenchen	Bayern
Germany	Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie	Muenchen	Bayern
Hungary	Semmelweis University-Department of Internal Medicine and Oncology	Budapest
Hungary	Clinexpert Kft. Bugat Pal Korhaz	Gyöngyös
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli	Campania
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	AOUI Verona	Verona	Veneto
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie	Kraków	Malopolskie
Poland	Szpital Uniwersytecki w Krakowie	Kraków	Malopolskie
Poland	Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego	Opole	Opolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie	Warsaw	Mazowieckie
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Parc de Salut Mar - Hospital del Mar	Barcelona	Cataluna
Spain	Hospital Universitario Reina Sofia	Córdoba	Cordoba
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Fundación Instituto Valenciano de Oncología	Valencia	Valenciana, Comunitat
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Alliance for Multispecialty Research, LLC	Merriam	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc	Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Hungary,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Lead-in Day -1 to Cycle 1 Day 28
Primary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary	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
Secondary	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
Secondary	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
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	Dose Escalation - ZN-c3 plasma exposure: AUC		From lead in day -1 visit through Cycle 1 Day 15
Secondary	Dose Escalation - ZN-c3 plasma exposure: Cmax		From lead in day -1 visit through Cycle 1 Day 15
Secondary	Dose Escalation - ZN-c3 plasma exposure: Tmax		From lead in day -1 visit through Cycle 1 Day 15
Secondary	Dose Escalation - Encorafenib plasma exposure: AUC		From lead in day -1 visit through Cycle 1 Day 15
Secondary	Dose Escalation - Encorafenib plasma exposure: Cmax		From lead in day -1 visit through Cycle 1 Day 15
Secondary	Dose Escalation - Encorafenib plasma exposure: Tmax		From lead in day -1 visit through Cycle 1 Day 15
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary	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.	From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary	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
Secondary	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
Secondary	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
Secondary	Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC		Lead in day 7
Secondary	Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax		Lead in day 7
Secondary	Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax		Day 7
Secondary	Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC		Cycle 1 Day 15
Secondary	Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax		Cycle 1 Day 15
Secondary	Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax		Cycle 1 Day 15
Secondary	Dose Expansion - ZN-c3 plasma exposure: AUC		Cycle 1 Day 15
Secondary	Dose Expansion - ZN-c3 plasma exposure: Cmax		Cycle 1 Day 15
Secondary	Tumor tissue BRAF V600E mutational status		From lead in day 1 visit through the last dose of any study intervention, up to 12 months