A Study to Evaluate the Efficacy of VVD-133214 in Combination With Pembrolizumab Compared With Pembrolizumab Alone in Participants With Advanced Cancer of the Colon or Rectum

September 15, 2026 updated by: Vividion Therapeutics, Inc.

A Phase 2, Randomized, Open-label Study of VVD-133214 in COmbination With Pembrolizumab Compared to Pembrolizumab Monotherapy in Participants With Advanced Colorectal Adenocarcinoma (CRC) Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (DMMR)

Researchers are looking for a better way to treat people with advanced colorectal cancer.

Colorectal cancer (cancer of the colon or rectum) is one of the most common cancers worldwide. Treatments include surgery, chemotherapy, radiotherapy, and immunotherapy; however, these treatments do not work for everyone, may cause serious adverse events or may stop working eventually. New treatments and treatment combinations are needed, especially for cancers that cannot be removed with surgery or that have spread to other parts of the body (called advanced or metastatic cancer).

Cells normally repair themselves when mistakes happen as they divide. But in some people with cancer, the repair system does not work properly because of a problem called dMMR (deficient mismatch repair). As a result, mistakes build up in the cell's DNA, leading to a condition called MSI (microsatellite instability). Over time, these changes can cause cells to grow and behave abnormally, contributing to the development and growth of cancer.

To survive, some cancer cells with dMMR or MSI rely on a protein called Werner helicase. This protein helps repair some of the DNA damage allowing them to keep growing. Because these cancer cells depend more on Werner helicase than healthy cells, blocking this protein may help stop cancer cells from surviving while having less effect on healthy cells.

The study drug, VVD-133214, is designed to block the Werner helicase protein. Blocking this protein may help stop cancer cells from growing, while causing less harm to healthy cells. VVD-133214 is being studied in combination with pembrolizumab, an approved immunotherapy that helps the immune system recognize and attack cancer cells.

This study will test the combination of VVD-133214 and pembrolizumab in people with advanced colorectal cancer with MSI and/or dMMR who have not yet received treatment for their advanced disease. The study aims to find the best dose of VVD-133214 in combination with pembrolizumab and to test whether the combination is more effective than pembrolizumab alone.

Participants will receive treatment with VVD-133214 for as long as it can help them and does not cause serious adverse events. Treatment with pembrolizumab will stop after two years. Participants can also stop treatment at any time.

During the study, participants will have regular visits with the study doctor for tests, scans, and check-ups. These visits help check how well the cancer is responding to the treatment and monitor the participants' health.

The study will also monitor adverse events, which are any new or worsening medical problems that can happen during the study. Doctors record all adverse events, irrespective of whether the study doctor believes they are related to the study treatments, to help ensure participants' safety throughout the study.

After stopping treatment, participants will return for follow-up visits: 30 days after their last dose of VVD-133214 and/or 100 days after their last dose of pembrolizumab. After that, participants will have long-term follow-up visits every 90 days for as long as they agree to continue participating in follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Argentina
      • Mar Del Plata, Buenos Aires,, Argentina, 7600
        • Not yet recruiting
        • Investigaciones Oncológicas C Colón
    • Buenos Aires
      • Buenos Aires, Buenos Aires, Argentina, C1199ABB
        • Not yet recruiting
        • Hospital Italiano de Buenos Aires
      • Buenos Aires, Buenos Aires, Argentina, C1414
        • Not yet recruiting
        • Centro Medico Fleischer
      • Buenos Aires, Buenos Aires, Argentina, C1426ANZ
        • Not yet recruiting
        • Instituto Alexander Fleming
    • Córdoba Province
      • Córdoba, Córdoba Province, Argentina, X5000JHQ
        • Not yet recruiting
        • Sanatorio Allende | Departamento de Investigación Clínica
    • Río Negro Province
      • Bariloche, Río Negro Province, Argentina, RP82 8400
        • Not yet recruiting
        • Fundacion INTECNUS
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, S2000GAP
        • Not yet recruiting
        • Sanatorio Parque - Oncology
  • Belgium
      • Ghent, Belgium, 9000
        • Not yet recruiting
        • UZ Gent - Digestive Oncology
      • Roeselare, Belgium, 8800
        • Not yet recruiting
        • AZ Delta - Digestive oncology
    • Brussels Capital
      • Brussels, Brussels Capital, Belgium, 1070
        • Not yet recruiting
        • Institut Jules Bordet - Clinique D'Oncology
    • Flemish Brabant
      • Leuven, Flemish Brabant, Belgium, 3000
        • Not yet recruiting
        • UZ Leuven - Digestive oncology
    • Hainaut
      • La Louvière, Hainaut, Belgium, 7100
        • Not yet recruiting
        • CHU Helora - Hopital de La Louvière - Site Jolimont - Oncology department
  • Brazil
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29047-660
        • Not yet recruiting
        • Hospital Evangélico de Cachoeiro de Itapemirim
    • Goiás
      • Goiânia, Goiás, Brazil, 74605-070
        • Not yet recruiting
        • Hospital Araujo Jorge Associaçao de Combate ao Cancer em Goias
    • Rio Grande do Sul
      • Ijuí, Rio Grande do Sul, Brazil, 98700-000
        • Not yet recruiting
        • Nucleo de Ensino e Pesquisa do Hospital de Clinicas de Ijuí
      • Pelotas, Rio Grande do Sul, Brazil, 96020-080
        • Not yet recruiting
        • Unidade de Pesquisas Clinicas em Oncologia
    • São Paulo
      • Bauru, São Paulo, Brazil, 17033-490
        • Not yet recruiting
        • NAIC - Instituto do Cancer
      • Jaú, São Paulo, Brazil, 14784-400
        • Not yet recruiting
        • Fundacao Pio XII - Hospital de Cancer de Barretos
      • São Paulo, São Paulo, Brazil, 01246-000
        • Not yet recruiting
        • Instituto do Cancer do Estado de Sao Paulo
      • São Paulo, São Paulo, Brazil, 01308-050
        • Not yet recruiting
        • Hospital Sirio Libanes - Oncology_Sao Paulo
  • China
    • Anhui
      • Bengbu, Anhui, China, 233004
        • Not yet recruiting
        • the First Affiliated Hospital of Bengbu Medical College
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Not yet recruiting
        • Beijing Cancer Hospital - Oncology Department
    • Fujian
      • Fuzhou, Fujian, China, 350014
        • Not yet recruiting
        • Fujian Cancer Hospital
    • Guangdong
      • Guangzhou, Guangdong, China, 510655
        • Not yet recruiting
        • The Sixth Affiliated Hospital, Sun Yat-sen University
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150000
        • Not yet recruiting
        • Harbin Medical University Cancer Hospital
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Not yet recruiting
        • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
    • Shandong
      • Jinan, Shandong, China, 250117
        • Not yet recruiting
        • Shandong University - Shandong Cancer Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Not yet recruiting
        • Zhongshan hospital, Fudan university
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital Sichuan University
    • Yunnan
      • Kunming, Yunnan, China, 650118
        • Not yet recruiting
        • Yunnan Cancer Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Not yet recruiting
        • Zhejiang Cancer Hospital
      • Hangzhou, Zhejiang, China, 310016
        • Not yet recruiting
        • Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department
  • France
      • Besançon, France, 25030
        • Not yet recruiting
        • CHRU de Besancon - Hopital Jean Minjoz - Medical Oncology
      • Dijon, France, 21000
        • Not yet recruiting
        • Unicancer Dijon - Centre Georges Francois Leclerc - Oncologie medicale
      • Marseille, France, 13009
        • Not yet recruiting
        • Unicancer Marseille - Institut Paoli-Calmettes - Oncologie medicale
    • Brittany Region
      • Brest, Brittany Region, France, 29200
        • Not yet recruiting
        • CHU Brest - Hopital La Cavale Blanche - service oncologie medicale
  • Germany
    • Baden-Wurttemberg
      • Ulm, Baden-Wurttemberg, Germany, 89081
        • Not yet recruiting
        • Universitätsklinikum Ulm - Klinik für Innere Medizin I
    • Bavaria
      • Schweinfurt, Bavaria, Germany, 97422
        • Not yet recruiting
        • Leopoldina-Krankenhaus der Stadt Schweinfurt GmbH-Medizinische Klinik 2
    • Free and Hanseatic City of Hamburg
      • Hamburg, Free and Hanseatic City of Hamburg, Germany, 22763
        • Not yet recruiting
        • Asklepios Klinik Altona - Onkologie, Hämatologie, Palliativmedizin, Rheumatologie und Pneumologie
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60488
        • Not yet recruiting
        • Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
    • Lower Saxony
      • Oldenburg, Lower Saxony, Germany, 26133
        • Not yet recruiting
        • Klinikum Oldenburg - Klinik für Onkologie und Hämatologie
    • North Rhine-Westphalia
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Not yet recruiting
        • Universitaetsklinikum Essen - Innere Klinik (Tumorforschung)
    • State of Berlin
      • Berlin, State of Berlin, Germany, 12559
        • Not yet recruiting
        • DRK Kliniken Berlin-Köpenick - Darmzentrum
  • Greece
      • Athens, Greece, 11526
        • Not yet recruiting
        • Laiko General Hospital Of Athens- Oncology Department
      • Cholargos/ Athens, Greece, 155 62
        • Not yet recruiting
        • Metropolitan General Hospital -Oncologic Clinical Trials and Research Clinic
      • Pátrai, Greece, 265 04
        • Not yet recruiting
        • General University Hospital Of Patras- Division of Oncology, Department of Medicine
    • Attica
      • Athens, Attica, Greece, 115 22
        • Not yet recruiting
        • Saint Savvas Oncology Hospital -1st Internal Medicine - Oncology Department
      • Athens, Attica, Greece, 115 28
        • Not yet recruiting
        • General Hospital Of Athens Alexandra-Plasma Cell Dyscrasias Unit, Department of Clinical Therapeutics, N.K.U.A
    • Thessaloniki
      • Pylaia, Thessaloniki, Greece, 570 01
        • Not yet recruiting
        • Athens Medical Center S.A./ European Interbalkan Medical Center - 4th Department of Medical Oncology
  • Hong Kong
    • Hong Kong SAR
      • Hong Kong, Hong Kong SAR, Hong Kong, 00000
        • Not yet recruiting
        • Queen Mary Hospital
    • Kowloon
      • Kowloon, Kowloon, Hong Kong, 00000
        • Not yet recruiting
        • Hong Kong United Oncology Centre
    • New Territories
      • Shatin, New Territories, Hong Kong, 00000
        • Not yet recruiting
        • Prince of Wales Hospital
  • Italy
      • Milan, Italy, 20141
        • Not yet recruiting
        • Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
      • Naples, Italy, 80131
        • Not yet recruiting
        • A.O.U. Universita' Degli Studi Della Campania Luigi Vanvitelli - Oncoematologia
      • Roma, Italy, 00168
        • Not yet recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
      • Rozzano, Italy, 20089
        • Not yet recruiting
        • Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
    • Milan
      • Milan, Milan, Italy, 20162
        • Not yet recruiting
        • ASST Grande Ospedale Metropolitano Niguarda - Oncologia Falck
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • Not yet recruiting
        • Universiti Malaya Medical Centre - Clinical Oncology Department
      • Kuala Lumpur, Malaysia, 59200
        • Not yet recruiting
        • Cengild G.I. Medical Centre - Curie Oncology KL
    • Pulau Pinang
      • Perai, Pulau Pinang, Malaysia, 13700
        • Not yet recruiting
        • Sunway Medical Centre Penang - Department of Clinical Oncology
    • Sabah
      • Kota Kinabalu, Sabah, Malaysia, 88996
        • Not yet recruiting
        • Hospital Wanita Dan Kanak Kanak Sabah - Oncology and Radiotherapy
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Not yet recruiting
        • Hospital Umum Sarawak (Sarawak General Hospital) SGH
    • Selangor
      • Subang Jaya, Selangor, Malaysia, 47500
        • Not yet recruiting
        • Sunway Medical Centre - Medical Oncology
  • Mexico
      • Benito Juárez, Mexico, 03100
        • Not yet recruiting
        • Grupo Medico ASSET S.C
      • Guadalajara, Mexico, 44680
        • Not yet recruiting
        • Renati Innovation SAPI de CV
      • Mexico City, Mexico, 3810
        • Not yet recruiting
        • Oncare Viaducto Nápoles
      • Monterrey, Mexico, 64460
        • Not yet recruiting
        • Hospital Universitrio Dr. José Eleuterio González. Servicio de Oncologia
    • Mexico City
      • Mexico City, Mexico City, Mexico, 14080
        • Not yet recruiting
        • Instituto Nacional de Cancerologia
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 66278
        • Not yet recruiting
        • Hospital Zambrano Hellion
  • Netherlands
      • The Hague, Netherlands, 2545 AA
        • Not yet recruiting
        • HagaZiekenhuis - Oncologie Interne Geneeskunde
  • Poland
      • Bialystok, Poland, 15-027
        • Not yet recruiting
        • Białostockie Centrum Onkologii im. M. Skłodowskiej-Curie w Białymstoku Oddział Onkologii Klinicznej
      • Krakow, Poland, 30-727
        • Not yet recruiting
        • Pratia MCM Krakow
      • Krakow, Poland, 31-864
        • Not yet recruiting
        • Comarch Healthcare SA Centrum Medyczne iMed24
      • Lodz, Poland, 93-513
        • Not yet recruiting
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
      • Opole, Poland, 45-061
        • Not yet recruiting
        • Opolskie Centrum Onkologii
      • Otwock, Poland, 05-400
        • Not yet recruiting
        • Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina
      • Przemyśl, Poland, 37-700
        • Not yet recruiting
        • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu Oddział Onkologiczny z Pododdziałem Dziennej Chemioterapii
      • Siedlce, Poland, 08-110
        • Not yet recruiting
        • Mazowiecki Szpital Wojewódzki Siedleckie Centrum Onkologii Oddział Onkologii Klinicznej i Radioterapii
      • Skorzewo, Poland, 60-185
        • Not yet recruiting
        • Centrum Medyczne Pratia Poznan
      • Warsaw, Poland, 02-034
        • Not yet recruiting
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie Państwowy Instytut Badawczy- Oddział Warszawa Wawelska
      • Wroclaw, Poland, 50-417
        • Not yet recruiting
        • Pratia Wroclaw
  • Portugal
      • Coimbra, Portugal, 3004-561
        • Not yet recruiting
        • Unidade Local de Saúde de Coimbra, E.P.E. - Hospitais da Universidade de Coimbra - Serviço de Oncologia
      • Lisbon, Portugal, 1099-023
        • Not yet recruiting
        • Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E. - Serviço de Oncologia Médica
      • Lisbon, Portugal, 1169-050
        • Not yet recruiting
        • Unidade Local de Saúde de São José, E.P.E - Hospital de Santo António dos Capuchos - Serviço de Oncologia Médica
      • Lisbon, Portugal, 1649-035
        • Not yet recruiting
        • START Research Portugal - ULSS Maria - Unidade de Ensaios de Fase I Start Lisbon
      • Porto, Portugal, 4200-072
        • Not yet recruiting
        • Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. - Serviço de Oncologia Médica
  • Singapore
      • Singapore, Singapore, 258499
        • Not yet recruiting
        • OncoCare Cancer Centre | Gleneagles Medical Centre
      • Singapore, Singapore, 329563
        • Not yet recruiting
        • Curie Oncology | Farrer
      • Singapore, Singapore, 168583
        • Recruiting
        • National Cancer Center Singapore - Oncology Department
      • Singapore, Singapore, 119074
        • Not yet recruiting
        • National University Cancer Institute (NCIS)
  • South Korea
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Not yet recruiting
        • Seoul National University Bundang Hospital | Oncology
    • Seoul
      • Jongno -Gu, Seoul, South Korea, 03080
        • Not yet recruiting
        • Seoul National University Hospital | Oncology
      • Seoul, Seoul, South Korea, 03722
        • Not yet recruiting
        • Severance Hospital | Oncology
      • Seoul, Seoul, South Korea, 05505
        • Not yet recruiting
        • Asan Medical Center | Oncology
      • Seoul, Seoul, South Korea, 06351
        • Not yet recruiting
        • Samsung Medical Center | Oncology
  • Spain
      • Barcelona, Spain, 08003
        • Not yet recruiting
        • Hospital del Mar | Oncologia
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain, 15706
        • Not yet recruiting
        • Complexo Hospitalario Universitario De Santiago | Oncologia
    • Barcelona
      • Barcelona, Barcelona, Spain, 08035
        • Not yet recruiting
        • Hospital Universitari Vall D Hebron | Oncologia
    • Madrid
      • Madrid, Madrid, Spain, 28034
        • Not yet recruiting
        • Hospital Universitario Ramon Y Cajal | Oncologia Medica
    • Málaga
      • Málaga, Málaga, Spain, 20910
        • Not yet recruiting
        • Hospital Universitario Virgen De La Victoria | Oncologia Medica
    • Valencia
      • Valencia, Valencia, Spain, 46010
        • Not yet recruiting
        • Hospital Clinico Universitario De Valencia | Oncologia
  • Switzerland
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8091
        • Withdrawn
        • UniversitätsSpital Zürich (USZ) - Klinik für Medizinische Onkologie und Hämatologie
  • Taiwan
      • Keelung, Taiwan, 204201
        • Not yet recruiting
        • Keelung Chang Gung Memorial Hospital - Division of Hematology and Oncology
      • Taichung, Taiwan, 407219
        • Not yet recruiting
        • Taichung Veterans General Hospital | Division of Colorectal Surgery
      • Tainan, Taiwan, 71004
        • Not yet recruiting
        • Chi Mei Medical Center, Yongkang Branch
    • Kaohsiung
      • Kaohsiung City, Kaohsiung, Taiwan, 803
        • Not yet recruiting
        • Chang Gung Memorial Hospital Kaohsiung
    • Tainan
      • Tainan, Tainan, Taiwan, 704
        • Not yet recruiting
        • National Cheng Kung University Hospital
    • Taipei
      • Taipei, Taipei, Taiwan, 11217
        • Not yet recruiting
        • Taipei Veterans General Hospital
      • Taipei, Taipei, Taiwan, 10507
        • Not yet recruiting
        • Chang Gung Memorial Hospital at Linkou
  • Turkey (Türkiye)
      • Edirne, Turkey (Türkiye), 22030
        • Not yet recruiting
        • Trakya Univ. Tip Fak.
      • Gaziantep, Turkey (Türkiye), 27470
        • Not yet recruiting
        • Gaziantep Sehir Hastanesi -Medical Oncology Department
      • Istanbul, Turkey (Türkiye), 34865
        • Not yet recruiting
        • Kartal Dr Lutfi Kirdar Sehir Hastanesi- Medical Oncology
      • Samsun, Turkey (Türkiye), 55200
        • Not yet recruiting
        • VM Medical Park Samsun Hospital Medical Oncology Department
      • Yenimahalle, Turkey (Türkiye), 6170
        • Not yet recruiting
        • Ankara Etlik Sehir Hastanesi
    • Ankara
      • Bilkent Çankaya, Ankara, Turkey (Türkiye), 6800
        • Not yet recruiting
        • Ankara Bilkent Sehir Hastanesi
    • Istanbul
      • Kadıköy, Istanbul, Turkey (Türkiye), 34722
        • Not yet recruiting
        • İstanbul Medeniyet Üniversitesi Göztepe Süleyman Yalçın Şehir Hastanesi
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, NW1 2PG
        • Not yet recruiting
        • University College Hospital | Cancer Clinical Trials Unit
    • West Midlands
      • Coventry, West Midlands, United Kingdom, CV22DX
        • Not yet recruiting
        • University Hospital Coventry | Oncology
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Not yet recruiting
        • University of Arizona Cancer Center - North Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Not yet recruiting
        • University of Michigan Rogel Cancer Center
      • Detroit, Michigan, United States, 48202
        • Not yet recruiting
        • Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
    • West Virginia
      • Morgantown, West Virginia, United States, 26505
        • Not yet recruiting
        • Mary Babb Randolph Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1
  • Have a known microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) tumor status confirmed per local standard of care (SoC), and have histologically or cytologically documented advanced (unresectable and/or metastatic) colorectal adenocarcinoma (CRC)
  • No prior systemic treatment for metastatic disease and not amenable to curative resection
  • Participants must have documented MSI and/or dMMR tumor status determined as part of the routine diagnostic workup in a certified laboratory
  • Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to Sponsor/central laboratory for retrospective central testing including a copy of a redacted pathology report if available
  • Presence of measurable disease according to RECIST v1.1
  • Adequate hematologic and end-organ function, defined using laboratory results obtained within 14 days prior to first dose of study treatment
  • Females of childbearing potential must have negative serum pregnancy test before starting study treatment

Exclusion Criteria:

  • Prior systemic treatment for advanced CRC. Participants may have received prior adjuvant chemotherapy as long as disease progression occurred at least 12 months after the last dose of adjuvant treatment
  • Prior treatment with adjuvant immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents, etc.)
  • Known active or uncontrolled central nervous system (CNS) or brain metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous meningitis
  • Patients with active or history of autoimmune disease or immune deficiency that has required treatment in past 2 years
  • History of malignancy other than CRC, within 5 years prior to screening. Participants with Lynch syndrome are not excluded.
  • Participants requiring treatment with systemic immunosuppressive medication (such as corticosteroids) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
  • Participants with active hepatitis B, hepatitis C or HIV
  • Participants with known Werner Syndrome (WRN)
  • Prior treatment with any WRN helicase inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: VVD-133214 Dose 1 + Pembrolizumab
Participants will receive VVD-133214 in combination with pembrolizumab
Drug: VVD-133214
VVD-133214 will be administered orally
Drug: Pembrolizumab
Pembrolizumab will be administered by intravenous infusion (IV) every three weeks
Experimental: VVD-133214 Dose 2 + Pembrolizumab
Participants will receive VVD-133214 in combination with pembrolizumab
Drug: VVD-133214
VVD-133214 will be administered orally
Drug: Pembrolizumab
Pembrolizumab will be administered by intravenous infusion (IV) every three weeks
Active Comparator: Pembrolizumab
Participants will receive pembrolizumab only (monotherapy)
Drug: Pembrolizumab
Pembrolizumab will be administered by intravenous infusion (IV) every three weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Landmark progression-free survival (PFS) rate at 6 months, as assessed by the investigator
Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months)
Defined as the proportion of participants who are alive and free from disease progression as per RECIST v1.1
From start of study treatment until end of follow-up (up to approximately 36 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence and severity of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
Time Frame: From start of study treatment up to 30 days following the last dose of study drug (100 days after last administration of pembrolizumab)
From start of study treatment up to 30 days following the last dose of study drug (100 days after last administration of pembrolizumab)
Recommended Phase 2 Dose (RP2D) of VVD-133214 in combination with pembrolizumab
Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months)
The RP2D will be based on incidence, severity and frequency of adverse events, anti-tumor activity, PK/PD, and assessment of disease biomarkers for two doses of VVD-133214 combined with the standard of care (SoC) dose of pembrolizumab
From start of study treatment until end of follow-up (up to approximately 36 months)
Maximum plasma concentration observed (Cmax) following single and multiple doses of VVD-133214
Time Frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Predose and multiple timepoints post-dose, up to approximately 36 months
Time of maximum plasma concentration observed (Tmax) following single and multiple doses of VVD-133214
Time Frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Predose and multiple timepoints post-dose, up to approximately 36 months
Area under the plasma concentration-time curve (AUC) following single and multiple doses of VVD-133214
Time Frame: Predose and multiple timepoints post-dose, up to approximately 36 months
Predose and multiple timepoints post-dose, up to approximately 36 months
Overall response rate (ORR) according to RECIST v1.1 as assessed by the Investigator
Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months)
From start of study treatment until end of follow-up (up to approximately 36 months)
Disease control rate (DCR) according to RECIST v1.1 as assessed by the Investigator
Time Frame: From start of study treatment until end of follow-up (up to approximately 36 months)
From start of study treatment until end of follow-up (up to approximately 36 months)
Duration of response (DOR) according to RECIST v1.1 as assessed by the Investigator
Time Frame: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Median progression-free survival (mPFS) according to RECIST v1.1 as assessed by the Investigator
Time Frame: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vividion Therapeutics, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 11, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 15, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VVD-133214-02
  • 2026-525507-26-00 (Ctis)
  • 23236 (Other Identifier: Bayer ID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access.

As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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