ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

K-Group Beta

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: ZN-c3; Drug: Cetuximab; Drug: Encorafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05743036

Z0011001 (Other Identifier)

ZN-c3-016

Details and patient eligibility

About

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.

Enrollment: 82 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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82 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab

Treatment:

Drug: Encorafenib

Drug: Cetuximab

Drug: ZN-c3

Dose Expansion

Experimental group

Description:

Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab

Treatment:

Drug: Encorafenib

Drug: Cetuximab

Drug: ZN-c3