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Metastatic Colorectal CancerPhase 1NCT05743036

ZN-c3 in Adult Participants With Metastatic Colorectal Cancer

A Phase 1 study testing ZN-c3, Encorafenib and Cetuximab in people with Metastatic Colorectal Cancer, run by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc at 27 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
ZN-c3, Encorafenib and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
27 sitesin 7 countries
Study dates
27 Feb 2023to 9 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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 locations and contacts

27 sites in 7 countries.

27 sites in 7 countries

Spain6 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, Barcelona, 08035

  • Parc de Salut Mar - Hospital del Mar

    Barcelona, Catalonia, 08003

  • Hospital Universitario Reina Sofia

    Córdoba, Cordoba, 14004

  • Hospital Universitario La Paz

    Madrid, Madrid, 28046

  • Hospital Universitario Puerta de Hierro Majadahonda

    Madrid, Madrid, 28222

  • Fundación Instituto Valenciano de Oncología

    Valencia, Valenciana, Comunitat, 46009

Other trials in Spain

Germany5 sites

  • Hämatologie- Onkologie im Zentrum MVZ GmbH

    Augsburg, Bavaria, 86150

  • DRK Kliniken Berlin - Köpenick

    Berlin, State of Berlin, 12559

  • Institut für Klinisch Onkologische Forschung

    Frankfurt am Main, Hesse, 60488

  • Klinikum der Universität München Großhadern

    Munich, Bavaria, 81377

  • Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie

    Munich, Bavaria, 81737

Other trials in Germany

Italy5 sites

  • Istituto Europeo di Oncologia

    Milan, Milano, 20141

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, Milano, 20162

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale

    Naples, Campania, 80131

  • IRCCS Casa Sollievo della Sofferenza

    San Giovanni Rotondo, Foggia, 71013

  • AOUI Verona

    Verona, Veneto, 37126

Other trials in Italy

Poland4 sites

  • Szpital Uniwersytecki w Krakowie

    Krakow, Lesser Poland Voivodeship, 31-501

  • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

    Krakow, Lesser Poland Voivodeship, 31-826

  • Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Koszarowskiego

    Opole, Opole Voivodeship, 45-061

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie

    Warsaw, Masovian Voivodeship, 02-034

Other trials in Poland

United States3 sites

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Alliance for Multispecialty Research, LLC

    Merriam, Kansas, 66204

Other trials in United States

Australia2 sites

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Hungary2 sites

  • Semmelweis University-Department of Internal Medicine and Oncology

    Budapest, Budapest, 1083

  • Clinexpert Kft. Bugat Pal Korhaz

    Gyöngyös, 3200

Other trials in Hungary

About this study

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

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.

Being tested
ZN-c3, Encorafenib, Cetuximab
Keywords
Metastatic Colorectal Cancer, CRC, BRAF V600E
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZN-c3Drug

    ZN-c3 tablet by mouth, in combination with encorafenib

  • EncorafenibDrug

    Also called BRAFTOVI®

    Encorafenib capsule by mouth, in combination with ZN-c3

  • CetuximabDrug

    Also called ERBITUX®

    Infusion

Study groups in NCT05743036
Study groupRoleWhat they receive
Dose EscalationExperimentalParticipants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
Receives: Drug: ZN-c3; Drug: Encorafenib; Drug: Cetuximab
Dose ExpansionExperimentalParticipants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
Receives: Drug: ZN-c3; Drug: Encorafenib; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From Lead-in Day -1 to Cycle 1 Day 28

  2. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

Secondary outcomes (32)

  1. 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.

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  2. Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  3. Proportion of participants with dose modifications due to AEs in Dose Escalation Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  4. Proportion of participants with discontinuations due to AEs in Dose Escalation Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  5. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  6. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  7. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  8. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  9. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  10. Dose Escalation - ZN-c3 plasma exposure: AUC

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  11. Dose Escalation - ZN-c3 plasma exposure: Cmax

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  12. Dose Escalation - ZN-c3 plasma exposure: Tmax

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  13. Dose Escalation - Encorafenib plasma exposure: AUC

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  14. Dose Escalation - Encorafenib plasma exposure: Cmax

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  15. Dose Escalation - Encorafenib plasma exposure: Tmax

    Measured: From lead in day -1 visit through Cycle 1 Day 15

  16. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  17. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  18. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  19. 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.

    Measured: From first dose of any study intervention every 8 weeks during treatment, up to 12 months

  20. 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.

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  21. Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  22. Proportion of participants with dose modifications due to AEs in Dose Expansion Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  23. Proportion of participants with discontinuations due to AEs in Dose Expansion Phase

    Measured: From first dose of any study intervention through 28 days after the last dose of any study intervention

  24. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC

    Measured: Lead in day 7

  25. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax

    Measured: Lead in day 7

  26. Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax

    Measured: Day 7

  27. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC

    Measured: Cycle 1 Day 15

  28. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax

    Measured: Cycle 1 Day 15

  29. Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax

    Measured: Cycle 1 Day 15

  30. Dose Expansion - ZN-c3 plasma exposure: AUC

    Measured: Cycle 1 Day 15

  31. Dose Expansion - ZN-c3 plasma exposure: Cmax

    Measured: Cycle 1 Day 15

  32. Tumor tissue BRAF V600E mutational status

    Measured: From lead in day 1 visit through the last dose of any study intervention, up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2023
  2. Study start27 Feb 2023
  3. Primary completion16 Jul 2024
  4. Study completion9 Jul 2025

Why it stopped: Study terminated due to change in therapeutic landscape.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05743036
Sponsor's protocol ID
ZN-c3-016
Other IDs
Z0011001
Status last verified
Jan 2025
First submitted
26 Jan 2023
Last updated
8 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ZN-c3, Encorafenib and Cetuximab in people with Metastatic Colorectal Cancer, run by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc at 27 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Spain, Germany, Italy, Poland, United States and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated due to change in therapeutic landscape.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs) (time frame: From Lead-in Day -1 to Cycle 1 Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05743036.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2025.

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