Clinical trial NCT05743036: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
CRC
BRAF V600E
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2023-02-24
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: From Lead-in Day -1 to Cycle 1 Day 28
measure: Dose Expansion Phase - Objective response rate (ORR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcomes:
measure: 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
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with dose modifications due to AEs in Dose Escalation Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with discontinuations due to AEs in Dose Escalation Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Dose Escalation Phase - Objective response rate (ORR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Escalation Phase - Duration of Response (DOR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Escalation Phase - Progression Free Survival (PFS)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Escalation Phase - Disease Control Rate (DCR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Escalation Phase - Time to Response (TTR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Escalation - ZN-c3 plasma exposure: AUC
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Escalation - ZN-c3 plasma exposure: Cmax
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Escalation - ZN-c3 plasma exposure: Tmax
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Escalation - Encorafenib plasma exposure: AUC
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Escalation - Encorafenib plasma exposure: Cmax
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Escalation - Encorafenib plasma exposure: Tmax
timeFrame: From lead in day -1 visit through Cycle 1 Day 15
measure: Dose Expansion Phase - Duration of Response (DOR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Expansion Phase - Progression Free Survival (PFS)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Expansion Phase - Disease Control Rate (DCR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: Dose Expansion Phase - Time to Response (TTR)
timeFrame: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
measure: 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
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with dose modifications due to AEs in Dose Expansion Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Proportion of participants with discontinuations due to AEs in Dose Expansion Phase
timeFrame: From first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC
timeFrame: Lead in day 7
measure: Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax
timeFrame: Lead in day 7
measure: Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax
timeFrame: Day 7
measure: Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC
timeFrame: Cycle 1 Day 15
measure: Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax
timeFrame: Cycle 1 Day 15
measure: Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax
timeFrame: Cycle 1 Day 15
measure: Dose Expansion - ZN-c3 plasma exposure: AUC
timeFrame: Cycle 1 Day 15
measure: Dose Expansion - ZN-c3 plasma exposure: Cmax
timeFrame: Cycle 1 Day 15
measure: Tumor tissue BRAF V600E mutational status
timeFrame: From lead in day 1 visit through the last dose of any study intervention, up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Merriam
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Augsburg
country: Germany
facility: Hämatologie- Onkologie im Zentrum MVZ GmbH
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum der Universität München Großhadern
state: Bayern
city: Muenchen
country: Germany
facility: Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
state: Bayern
city: Frankfurt
country: Germany
facility: Institut für Klinisch Onkologische Forschung
state: Hessen
city: Berlin
country: Germany
facility: DRK Kliniken Berlin - Köpenick
city: Budapest
country: Hungary
facility: Semmelweis University-Department of Internal Medicine and Oncology
city: Gyöngyös
country: Hungary
facility: Clinexpert Kft. Bugat Pal Korhaz
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
state: Campania
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
state: Foggia
city: Verona
country: Italy
facility: AOUI Verona
state: Veneto
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
state: Malopolskie
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
state: Malopolskie
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
state: Mazowieckie
city: Opole
country: Poland
facility: Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego
state: Opolskie
city: Barcelona
country: Spain
facility: Parc de Salut Mar - Hospital del Mar
state: Cataluna
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Cordoba
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
Study officials:
References: