Triplezumab Combined With CAPEOX Regimen in Neoadjuvant Therapy for Locally Advanced Colon Cancer

Triplezumab Combined With CAPEOX Regimen Was Used in a Phase II Clinical Study of Neoadjuvant Therapy for Locally Advanced Colon Cancer With MSI-H /dMMR

According to the 2019NCCN guidelines, immunocheckpoint inhibitors are recommended for first-line treatment of metastatic colon cancer patients with high microsatellite instability (msi-h) or mismatched gene deletion (dMMR) who are not suitable for intensive treatment, and for all patients with second-line or above msi-h /dMMR treatment.This study is a single-center, single-arm phase II study of the use of triplezumab (JS001) combined with CAPEOX regimen in the neoadjuvant therapy of msi-h /dMMR for locally advanced colon cancer. The subjects received neoadjuvant therapy with triplezumab (JS001) combined with CAPEOX regimen, with one treatment cycle every 3 weeks and two cycles of surgery followed by pathological evaluation.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced Colon Cancer
• Intervention / Treatment: Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • Yefeng
      • Contact: Ye feng, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign written informed consent.
2. Age ≥18 years.
3. ECOG physical condition score ≤1.
4. Pathological diagnosis of msi-h /dMMR colon cancer.
5. The TNM stage of colon cancer was ct3/4nxm0 or ctxn1/2m0.
6. Never received anti-tumor treatment including but not limited to radiotherapy, chemotherapy and surgery.

7. The patient must have adequate organ function and meet the following laboratory test values during the screening period within 7 days before enrolling:

   • Absolute neutrophil cell count (ANC) ≥1.5x109/L, platelet ≥100x109/L, hemoglobin ≥90g/L.(in (Patients with no blood transfusion or growth factor support should be given for 7 days prior to blood collection.)
   • Serum creatinine ≤1.5× upper normal range (ULN) or estimated creatinine clearance ≥50mL/min.
   • Total bilirubin ≤1.5×ULN;If there is Gilbert syndrome or if the indirect bilirubin concentration indicates an extrahepatic source of bile The rise of erythrosin is ≤3×ULN.
   • Glutamate aminotransferase and glutamate aminotransferase (AST and ALT)≤3×ULN.
   • Aptt ≤1.5×ULN, and INR or PT≤1.5×ULN.
8. Fertile women must be willing to participate in the final CAPEOX programme during the study period and in conjunction with the triplezumab (JS001) Contraceptive measures were taken at least 120 days after administration, and urine or serum pregnancy tests were negative for 7 days prior to enrollment.
9. Unsterilized male subjects must be willing to participate during the study and at the end of the triplezumab (JS001) combined CAPEOX regimen Use contraception for at least 120 days after the first dose.
10. Good compliance, agreed to cooperate with the survival follow-up.

Exclusion Criteria:

1. Signs of distant metastasis.
2. The presence of complete obstruction, massive bleeding, or perforation associated with a colon tumor.
3. Previous use of immunocheckpoint inhibitors targeting ctla-4, pd-1 or pd-l1.
4. Have radiotherapy plan before or after operation.
5. A history of research on drug ingredients and severe allergic reactions to any monoclonal antibody.
6. Severe infection in the active stage or poorly controlled clinically.
7. Symptomatic congestive heart failure (New York heart association grade ii-iv) or symptomatic, poorly controlled arrhythmia often; Any arterial thromboembolic events that occurred or occurred within 6 months prior to inclusion included myocardial infarction, unstable angina cerebrovascular accident or transient ischemic attack; Deep vein thrombosis, pulmonary embolism, or any other serious condition occurred 3 months prior to enrollment, History of thromboembolism (implantable venous infusion port or catheter-induced thrombosis, or superficial venous thrombosis is not seen severe thromboembolism).
8. Subjects with any active, known or suspected autoimmune disease.History of autoimmune disease, including but not limited myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis related to antiphospholipid syndrome, wegener's granulomatosis, sjogren's syndrome, guillain-barre complex signs, multiple sclerosis, vasculitis, or glomerulonephritis.
9. Patients with autoimmune hypothyroidism who receive stable dose hormone replacement therapy are eligible to participate in this study investigate.
10. Patients with vitiligo or who have had complete remission of childhood asthma may be included without any intervention in adulthood.
11. Asthma patients requiring intermittent use of bronchodilators, inhaled steroids, or topical injections were not excluded from the study outside.
12. Use of corticosteroids (>10mg/ day prednisone or equivalent) or other within 14 days prior to initial administration subjects who received systemic therapy with immunosuppressive agents.In the absence of active autoimmune disease, inhalation or topical administration of corticosteroids and adrenal hormone replacement at dose ≤10mg/ day of prednisone.
13. Subjects with highly suspected interstitial lung disease, or interstitial lung disease requiring steroid hormone therapy, or other severe cases were excluded diseases that seriously affect lung function.
14. Get a live vaccine 4 weeks before joining.
15. Patients with other active malignancies within 5 years prior to the first use of the study drug.Localized tumors that have been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc into the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: The experimental group	Drug: Toripalimab; Toripalimab union CAPEOX scheme： Toripalimab 240mg, ivgtt, Q3w Oxaliplatin 130mg/m2,ivgtt, Q3w capecitabine 1000mg/m2, p.o Q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effectiveness of neoadjuvant therapy	The main pathological response rate of neoadjuvant therapy	6 weeks

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Anticipated): March 4, 2021
• Study Completion (Anticipated): March 4, 2021

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 11, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: JS001-ISS-CO24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No