Neoadjuvant ADG126 and Pembrolizumab in Locally Advanced Colorectal Cancer

July 22, 2025 updated by: National University Hospital, Singapore

Phase II Trial of Neoadjuvant ADG126 and Pembrolizumab in Locally Advanced Colorectal Cancer

This is a single site, open-label, single-arm phase II study to determine feasibility, tolerability, and preliminary efficacy of neoadjuvant ADG126 and pembrolizumab in stage II or III colorectal cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This clinical trial aims to enrol patients with stage II or III colorectal cancer. At least 16, and up to 20 patients will be recruited. Patients will be given two cycles of neoadjuvant immunotherapy (ADG 126 and pembrolizumab). They will be assessed for response at 4 weeks or if they develop clinical symptoms of progression. Patients will undergo surgery 2 weeks (± 1 week) after the second dose of study treatment and within 8 weeks of study enrolment.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • 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 Backup

Study Locations

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Willing and able to provide written informed consent for the trial.
  2. Be ≥ 21 years of age on the date of signing informed consent.
  3. ECOG performance status of 0 or 1.
  4. Histologically confirmed colorectal adenocarcinoma. Rectal cancers allowed if the treatment plan was upfront surgery with no need for any neoadjuvant chemotherapy or radiation.
  5. Clinical stage II (T3-4, N-) or stage III (Tany, N+).
  6. No evidence of distant metastases.
  7. Radiologically measurable or clinically evaluable disease.

  8. Negative pregnancy test done 72 hours before registration, for women of childbearing potential.

    Subjects of childbearing potential must be willing to use an adequate method of contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormone contraceptives, or double barrier method (diaphragm plus condom). Contraception, for the course of the study starting with the first dose of study medication through 150 days after the last dose of study medication. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    Non-childbearing potential is defined as follows:

    • ≥45 years of age and has not had a menstrual period for >1 year
    • Patients who have been amenorrhoeic for <2 years without a history of hysterectomy and oophorectomy must have a follicle-stimulating hormone value in the postmenopausal range upon screening evaluation
    • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure; otherwise, the patient must be willing to use 2 adequate barrier methods throughout the study.

  9. Demonstrate adequate organ function as defined below, all screening labs should be performed within 28 days of treatment initiation.

    1. Haematological

      • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL.
      • Platelets greater than or equal to 100,000/mcL.
      • Haemoglobin greater than or equal to 9 g/dL.

    2. Renal

      · Serum creatinine OR Measured or calculated creatinine clearance (by Cockcroft-Gault equation), Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance greater than or equal to 60 mL/min for subject with creatinine levels greater than 1.5 x ULN

    3. Hepatic

      • Serum total bilirubin less than or equal to 1.5 x ULN OR Direct bilirubin less than or equal to ULN for subjects with total bilirubin levels greater than 1.5 x ULN.
      • AST and ALT less than or equal to 2.5 x ULN.
    4. Coagulation · International Normalised Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT). For patients not taking warfarin: INR less than or equal to 1.5 or PT less than or equal to 1.5 x ULN; and either PTT or aPTT less than or equal to 1.5 x ULN. Patients on warfarin may be included on a stable dose with a therapeutic INR less than 3.5.

Exclusion Criteria:

  1. Recurrent colorectal cancer.
  2. Prior radiation therapy, chemotherapy, immunotherapy, or surgery for colorectal cancer.
  3. Tumour is causing symptomatic bowel obstruction (patients who have a temporary diverting stoma are eligible).
  4. Other invasive malignancy ≤5 years prior to registration.
  5. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of non-physiologic dose immunosuppressive therapy within 7 days prior to first dose of trial treatment.
  6. Active autoimmune disease requiring systemic treatment within the past 2 years or documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents at non-physiologic doses.
  7. Active infection requiring systemic therapy.
  8. Received prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  9. Experienced ≥ Grade 3 immune-related adverse event with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
  10. Other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
  11. Known history of Human Immunodeficiency Virus.
  12. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  13. Women who are pregnant or breastfeeding, or men expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening visit through 150 days after the last dose of study medication.
  14. Concurrent medical or psychiatric condition or disease which, in the investigator's judgement, would make them inappropriate candidates for entry into the study. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  15. Received a live vaccine within 30 days of planned start of study medication.
  16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrolment.
  17. History of interstitial lung disease.
  18. Known hypersensitivity to ADG126 or pembrolizumab components or excipients.

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: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ADG126 in combination with pembrolizumab
ADG 126 will be administered with Pembrolizumab on Day 1 and Day 22 or Pembrolizumab on Day 22 alone depending on the dose level.
Drug: ADG126
Administered via intravenous infusion on Day 1 only (Q6W) or Day 1 and Day 22 (Q3W).
Drug: Pembrolizumab
Administered via intravenous infusion on Day 1 and Day 22.
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Major Pathologic Response (MPR)
Time Frame: Up to 4 months
MPR is defined as less than or equal to 10% of residual viable tumour in the surgical specimen.
Up to 4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Pathologic Complete Response (pCR)
Time Frame: Up to 4 months.
pCR is defined as the absence of any residual viable tumour in the surgical specimen.
Up to 4 months.
Objective Response Rate (ORR)
Time Frame: Up to 4 months.
Determined by the investigator according to RECIST 1.1 criteria.
Up to 4 months.
Disease-free survival (DFS)
Time Frame: Up to 5 years from surgery.
DFS is defined as the time from surgery to the first occurrence of disease relapse or death from any cause.
Up to 5 years from surgery.
Adverse Events and Serious Adverse Events
Time Frame: From screening to 30 days after last day of study participation.
Graded using NCI CTCAE toxicity grading v5.0
From screening to 30 days after last day of study participation.

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Collaborators

Adagene Inc

Investigators

  • Principal Investigator: Wei Peng Yong, MD, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 14, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

February 24, 2025

First Submitted That Met QC Criteria

February 24, 2025

First Posted (Actual)

February 26, 2025

Study Record Updates

Last Update Posted (Actual)

July 25, 2025

Last Update Submitted That Met QC Criteria

July 22, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR01/01/24

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Locally Advanced Colorectal Cancer

Clinical Trials on ADG126

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe