Cadonilimab as Neoadjuvant Therapy in Resectable Stage II-III MSI-H/dMMR Colorectal Cancer

NCT05913570 | Unknown Phase 2

• 1 other identifier: 2023-061-002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H.

Conditions

Colorectal Cancer; Mismatch Repair-deficient (dMMR); Microsatellite Instability-high (MSI-H); Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rates

  Proportion of patients experiencing a pCR to perioperative PD-1/CTLA-4 bi-specific antibody

  1 year

Secondary Outcomes (5)

• Major pathological response rates

  1 year

• R0 resection rates

  1 year

• Relapse-free survival (DFS)

  3 years

• The incidence of Treatment-related Adverse Events

  1 year

• Number of participants with any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose

  1 year

Study Arms (1)

Experimental: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody

EXPERIMENTAL

Neoadjuvant therapy with Cadonilimab

Drug: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody

Interventions

Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody DRUG

10mg/kg, Q3W for 4 cycles

Also known as: Neoadjuvant therapy with Cadonilimab

Experimental: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Male or female subjects \> 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histological or cytological documentation of adenocarcinoma of the colon or rectum; Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) in local site; For colon cancer must be determined by CT or MRI scans as locally advanced (T4) or cN1-2 \[with the definition of a clinically positive lymph node being any node ≥ 1.0 cm\]). Participants should be eligible for radical resection of R0.
• At least one measurable lesion as defined by RECIST 1.1
• Willing and able to provide 2ml blood and archived tumor tissue sample for MSI status testing. Patients who do not have adequate archival tumor tissue available should undergo a fresh tumor biopsy
• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.
• Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 120 days following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel.

You may not qualify if:

• Previous any systemic anticancer therapy for colorectal cancer disease, including chemotherapy, radiothapy or immunotherapy
• Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
• Subjects with known allergy to monoclonal antibodies
• Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 2 years prior to study drug treatment.
• Concurrent with active autoimmune disease or Participants with a history of autoimmune disease who may recur
• Subjects receiving immunosuppressive agents (such as steroids, or corticosteroids at physiologic replacement doses, equivalent to ≤ 10 mg prednisone daily ) for any reason within 14 days before the study drug treatment.
• Uncontrolled hypertension or hyperglycemia within 14 days before the study drug treatment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrent within 14 days of study drug treatment)
• History of interstitial lung disease, noninfectious pneumonia, or poorly controlled lung disease (including pulmonary fibrosis, acute lung disease).
• Active systemic bacterial, viral, or fungal infection， requiring systemic treatment within 14 days before study drug treatment.
• Positive test for hepatitis B virus surface antigen with HBV DNA\> 500 IU/mL（\> 2500copies/mL）at screening or untreated Chronic hepatitis B
• Positive test for hepatitis C virus ribonucleic acid (if antihepatitis C virus antibody tested positive) at screening;
• Known history of testing positive for human immunodeficiency virus (HIV)
• Major surgery for any reason, except diagnostic biopsy, within 28 days of the first administration of study drug. The subject must fully recovered from prior treatment before the first administration of study drug
• Previous allogeneic stem cell transplantation or organ transplantation

Sponsors & Collaborators

• LiuYing: lead

Study Sites (1)

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

Zhengzhou, Henan, 450008, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Ying Liu, MD

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Liu, MD

CONTACT

+86-13783604602; Yaya7207@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Cadonilimab was approved in China in June 2022 for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 22, 2023
• Study Start: June 20, 2023
• Primary Completion: December 20, 2023
• Study Completion: December 20, 2023
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)