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Metastatic Colorectal Cancer (CRC)Phase 1/2NCT07807800

A Study of DES-1357 in People With Deficient Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer (mCRC)

A Phase 1/2 study testing DES-1357 in people with Metastatic Colorectal Cancer (CRC), run by D. E. Shaw Research, LLC.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

This study is conducted sequentially in 3 parts. The primary objective for Part 1 is to determine the maximum tolerated dose of DES-1357 in participants with confirmed dMMR/MSI-H colorectal cancer (CRC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer (CRC)
What is being tested?
DES-1357
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
No sites listed yet
Study dates
3 Dec 2026to 2 Jul 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Individuals must meet all of the following criteria to be included in the study:
  • Have read, understood, and signed the Informed Consent Form (ICF).
  • Male or female aged greater than or equal to (>=) 18 years at the time of signing the ICF.
  • Histologically or cytologically confirmed carcinoma of the colon and/or rectum deemed unresectable and/or with evidence of metastases, that has been cytologically or genetically confirmed as dMMR, and/or MSI-H.
  • Demonstrated disease progression and/or intolerability to prior treatment with any of the following: pembrolizumab, nivolumab (±ipilimumab), dostarlimab, chemotherapy (ie, FOLFOX, FOLFIRI, CAPEOX, or FOLFOXIRI [±bevacizumab]), encorafenib/cetuximab, trastuzumab-based combinations, KRAS inhibitor/EGFR inhibitor, regorafenib, or TAS-102 (±bevacizumab)
  • Measurable disease according to RECIST version 1.1.
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  • Adequate organ function:
  • Absolute neutrophil count >=1,500 cells per/μL
  • Platelets >=100,000 cells/μL
  • Hemoglobin >=9 grams per deciliter (g/dL)
  • Total bilirubin less than or equal to (<=) 1.5*the Upper Limit of Normal (ULN) (<=3*ULN if attributable to known Gilbert's syndrome)
  • Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) <=5*ULN if liver metastasis present; if liver metastasis is not present, then AST/ALT <=3*ULN.
  • Measured creatinine clearance >=60 milliliter per minute (mL/min) per Cockcroft-Gault formula.
  • Prothrombin time (PT) or international normalized ratio and Partial Thromboplastin Time (PTT) <=1.5*ULN, unless receiving anti-coagulant therapy; Note: activated PTT can be used instead of PTT if it is the site's standard practice.
  • Have agreed to tissue sampling (biopsy [if available], baseline archival tissue, and/or fresh frozen tissue [if available]).
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • An estimated life expectancy of at least 3 months based on investigator judgment.
  • Women of childbearing potential (WOCBP) and men must agree to use 2 highly effective methods of contraception or practice abstinence from 4 weeks before the first dose of DES-1357, throughout the study, and for 6 months after the last dose of DES-1357; men must refrain from donating or banking sperm during the same period.
  • Negative serum pregnancy test result at screening and on Cycle 1 Day 1 for WOCBP.
  • Female participants who are not WOCBP should meet at least 1 of the following criteria:
  • have undergone a documented hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy; have medically confirmed ovarian failure, or achieved postmenopausal status (defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, or have a serum follicle-stimulating hormone level within the laboratory's reference range for postmenopausal women).

Who cannot join

  • Individuals meeting any of the following criteria at screening or baseline are ineligible to participate in this study:
  • Cytologically and/or genetically confirmed proficient mismatch repair (pMMR) and/or MSS.
  • Evidence of severe gastrointestinal malabsorption as determined by the investigator.
  • History or presence of dysphagia.
  • Symptomatic or clinically significant bowel obstruction, perforation, or high risk for obstruction as determined by the investigator.
  • Hypersensitivity to any component of DES-1357.
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  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) greater than (>) 470 milliseconds (msec) based on triplicate 12-lead ECGs obtained at screening.
  • Has an active infection.
  • Has known Human Immunodeficiency Virus (HIV) infection that is not under control. All of these criteria are required: undetectable viral RNA, CD4+ counts/levels >=350, no history of Acquired Immune Deficiency Syndrome (AIDS)-defining opportunistic infection within the past 12 months, and clinically stable for at least 3 months on the same anti-HIV medications.
  • Has active or uncontrolled hepatitis B or C infection. Participants are eligible if they:
  • Have been curatively treated for hepatitis C virus infection as demonstrated clinically and by viral serologies
  • For hepatitis B, if the participant has a positive hepatitis B surface antigen result, viral load must be below 2000 international units per milliliter (IU/mL) in the absence of antiviral therapy for the last 12 weeks, and AST/ALT <=3*ULN
  • Uncontrolled diabetes as determined by the investigator.
  • Cardiovascular and/or cerebrovascular event in the prior 6 months before screening.
  • Has received prior treatment with a Werner Syndrome Helicase (WRN) inhibitor.
  • Has been diagnosed with Werner Syndrome.
  • Primary Central Nervous System (CNS) tumor/CNS metastasis.
  • Ongoing toxicities from prior anti-cancer therapy that have not resolved to baseline or grade <=1 (according to NCI-CTCAE version 6.0), except for alopecia and endocrinopathies that are stable under medication.
  • Is pregnant or breastfeeding, is planning to become pregnant during the study.
  • Is planning to donate/bank or retrieve eggs (ova, oocytes) or donate sperm during the study.

About this study

Official title: A Phase 1/2 Adaptive Study of DES-1357 in Participants With Deficient Mismatch Repair (dMMR) and/or Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer (mCRC)

This study is conducted sequentially in 3 parts. The primary objective for Part 1 is to determine the maximum tolerated dose of DES-1357 in participants with confirmed dMMR/MSI-H colorectal cancer (CRC). The primary objective for Part 2 is to assess the chronic tolerability and to identify the recommended Phase 2 dose (RP2D), to evaluate preliminary antitumor activity of the selected dose level of DES-1357, and to assess the pharmacokinetics (PK) and pharmacodynamics of DES-1357. The primary objective for Part 3 is to evaluate antitumor activity of the selected dose level of DES-1357.

Being tested
DES-1357
Keywords
Mismatch Repair Deficiency, Microsatellite Instability High, Colorectal cancer, Colorectal Neoplasms
Medical subject headings
Colorectal Neoplasms, Turcot syndrome

What participants receive

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

  • DES-1357Drug

    DES-1357 oral capsules.

Study groups in NCT07807800
Study groupRoleWhat they receive
Part 1: Dose EscalationExperimentalParticipants will receive DES-1357 orally once daily (QD) in 21-day treatment cycles with a starting dose of 150 milligrams (mg). The planned escalation dose levels are 300 and 600 mg to identify the maximum tolerated dose (MTD) for DES-1357.
Receives: Drug: DES-1357
Part 2: Dose Optimization - Dosing Schedule AExperimentalParticipants will receive DES-1357 orally QD in Dosing Schedule A. The dosing schedules will be selected based on the escalation ranges of Part 1, to determine the RP2D for expansion in Part 3.
Receives: Drug: DES-1357
Part 2: Dose Optimization - Dosing Schedule BExperimentalParticipants will receive DES-1357 orally QD in Dosing Schedule B. The dosing schedules will be selected based on the escalation ranges of Part 1, to determine the RP2D for expansion in Part 3.
Receives: Drug: DES-1357
Part 3: Dose ExpansionExperimentalParticipants will receive DES-1357 orally QD at the RP2D determined in Part 2 to further assess its efficacy and safety.
Receives: Drug: DES-1357

What is being measured

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

  1. Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

    A DLT is a toxicity that occurs during cycle 1 that meets the protocol-defined DLT criteria and is graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0

    Measured: Part 1: Cycle 1 (Cycle length=21 days)

  2. Part 2: Incidence and Severity of Treatment- related Treatment Emergent Adverse Events (TEAEs) Through at least 3 Cycles of DES-1357

    A TEAE is defined as an AE with onset dates on or after the start of the study treatment or AEs that started prior to the start of the study treatment but worsened in severity after start of the study treatment.

    Measured: Part 2: From the first dose of DES-1357 through at least 3 treatment cycles (Cycle length=21days)

  3. Part 2: Best Overall Response (BOR)

    Best overall response is defined as the single best patient level response category (Complete Response [CR], Partial Response [PR], Stable Disease [SD], Progressive disease [PD], or Not Evaluable [NE]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    Measured: Part 2: From baseline through disease progression or end of treatment (EOT); tumor assessments every 8 weeks and at the EOT visit; assessed up to approximately 11 months

  4. Part 2: Maximum Observed Concentration (Cmax) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  5. Part 2: Time to Maximum Concentration (Tmax) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  6. Part 2: Area Under the Curve (AUC) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  7. Part 2: Half Life (t1/2) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  8. Part 2: Clearance (CL) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  9. Part 2: Volume of Distribution (Vd) of DES-1357

    Measured: Part 2: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  10. Part 2: Change in Pharmacodynamic Markers Levels Following Treatment With DES-1357

    Blood and tumor tissue samples will be collected for pharmacodynamic assessments. Biomarker evaluations may include circulating tumor Deoxyribonucleic Acid (ctDNA), carcinoembryonic antigen (CEA), Werner Syndrome Helicase (WRN) expression, phospho-H2AX expression, and other exploratory molecular analyses performed using immunohistochemistry and Ribonucleic Acid (RNA) sequencing methods.

    Measured: Part 2: Blood Samples: At Day 1 (pre-dose) of Cycles 1, 2, 3, 5, 7, and 9; Tumor tissue: At Screening and Cycle 1 Day 15 (±3 days, pre-dose) (Cycle length=21days)

  11. Part 3: Objective Response Rate (ORR) by Independent Review Committee (IRC)

    ORR is defined as the percentage of participants with a confirmed objective response (CR or PR) as determined per RECIST Version 1.1.

    Measured: Part 3: From baseline through EOT; tumor assessments every 8 weeks and at the EOT visit; assessed up to approximately 8 months

Secondary outcomes (17)

  1. Part 1: Number of Participants With Treatment-related Adverse Events (AEs) Including TEAEs and Serious AEs

    Participants with treatment related AEs, TEAEs and SAEs will be reported, plus treatment-related delays, dose reductions, and/or treatment discontinuations.

    Measured: Part 1: From the first dose of DES-1357 through 30 days after the last dose (Cycle length=21 days)]

  2. Part 2: ORR According to RECIST Version 1.1

    ORR is defined as the percentage of participants with a confirmed objective response (CR or PR) as determined per RECIST Version 1.1.

    Measured: Part 2: From baseline through EOT; tumor assessments every 8 weeks and at the EOT visit; assessed up to approximately 11 months

  3. Part 2 and Part 3: Disease Control Rate (DCR) According to RECIST Version 1.1

    DCR is defined as the percentage of participants who achieve best response of CR, PR, or SD per RECIST version 1.1.

    Measured: Part 2 and Part 3: From baseline through EOT; tumor assessments every 8 weeks and at the EOT visit; assessed up to approximately 11 months

  4. Part 3: Duration of Response (DOR) According to RECIST Version 1.1

    DOR is defined as the time from the first objective response (CR or PR) to the first documented PD per RECIST version 1.1 or death.

    Measured: Part 3: From first documented objective response until first documented PD or death; assessed up to approximately 8 months

  5. Part 1 and Part 3: Maximum Observed Concentration (Cmax) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  6. Part 1 and Part 3: Time to Maximum Concentration (Tmax) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  7. Part 1 and Part 3: Area Under the Curve (AUC) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  8. Part 1 and Part 3: Half Life (t1/2) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  9. Part 1 and Part 3: Clearance (CL) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  10. Part 1 and Part 3: Volume of Distribution (Vd) of DES-1357

    Measured: Part 1 and Part 3: Cycle 1 Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose; Cycle 1 Day 15: predose, 1, 2, 4, 8, 12 and 24 hours postdose; Cycle 1 Days 3, 5, and 21: at predose (Cycle length=21 days)

  11. Part 1 and Part 3: Change in Pharmacodynamic Markers Level of DES-1357

    Blood and tumor tissue samples will be collected for pharmacodynamic assessments. Biomarker evaluations may include ctDNA, CEA, WRN expression, phospho-H2AX expression, and other exploratory molecular analyses performed using immunohistochemistry and RNA sequencing methods.

    Measured: Part 1 and Part 3: Blood Samples: At Day 1 (pre-dose) of Cycles 1, 2, 3, 5, 7, and 9; Tumor tissue: At Screening and Cycle 1 Day 15 (±3 days, pre-dose) (Cycle length=21days)

  12. Part 2: ORR by an IRC According to RECIST Version 1.1

    Part 2: ORR is defined as the percentage of participants with a confirmed objective response (CR or PR) as determined per RECIST Version 1.1.

    Measured: Part 2: From baseline through EOT; tumor assessments every 8 weeks and at the EOT visit; assessed up to approximately 11 months

  13. Part 2: DCR by an IRC According to RECIST Version 1.1

    Part 2: DCR is defined as the percentage of participants who achieve best response of CR, PR, or SD per RECIST version 1.1.

    Measured: Part 2: From baseline through EOT; tumor assessments every 8 weeks and at the EOT; assessed up to approximately 11 months

  14. Part 2 and Part 3: Characterization of Biomarker Profiles Following Treatment With DES-1357

    Blood and tumor tissue samples will be collected for biomarker analyses. Biomarker assessments may include Deoxyribonucleic Acid (DNA) damage/replication stress markers, ctDNA, WRN expression, and other relevant molecular biomarkers.

    Measured: Part 2 and Part 3: Blood Samples: At Day 1 (pre-dose) of Cycles 1, 2, 3, 5, 7, and 9; Tumor tissue: At Screening and Cycle 1 Day 15 (±3 days, pre-dose) (Cycle length=21days)

  15. Part 3: European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ C30) Questionnaire

    Quality-of-life will be assessed through a participant-reported outcome using EORTC QLQ C30

    Measured: Part 3: Screening, and at Cycle 1 Days 1, 8, 15, 21 and at Day 21 for subsequent cycles up to 37 days after last dose of DES-1357 (Cycle length=21days)

  16. Part 3: Progression-Free Survival (PFS)

    PFS is defined as the time from the first dose of DES-1357 to the earlier of the date of the first documented disease progression (per RECIST version 1.1) or death due to any cause.

    Measured: Part 3: From first dose of DES-1357 up to first documented disease progression or death; assessed for up to approximately 8 months

  17. Part 3: Overall Survival (OS)

    OS is defined as the time from the date of the first dose of study treatment to the date of death due to any cause.

    Measured: Part 3: From first dose of DES-1357 to date of death due to any cause; assessed for up to approximately 8 months

Timeline

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

  1. First posted8 Sep 2026
  2. Study start3 Dec 2026 (estimated)
  3. Primary completion2 Jul 2028 (estimated)
  4. Study completion2 Jul 2028 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
88 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07807800
Sponsor's protocol ID
DES-1357-101
Other IDs
2026-527769-30-00
Status last verified
Sep 2026
First submitted
2 Sep 2026
Last updated
8 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DES-1357 in people with Metastatic Colorectal Cancer (CRC), run by D. E. Shaw Research, LLC.

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 21 inclusion and 20 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: opening soon, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Part 1: Cycle 1 (Cycle length=21 days)). The study lists 11 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 NCT07807800.

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 Sep 2026.

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