PD1 Antibody Combined With mFOLFOX6 Neoadjuvant Therapy for Advanced Resectable Metastatic Colon Cancer

PD1 Antibody Combined With mFOLFOX6 Neoadjuvant Therapy for Advanced Resectable Metastatic Colon Cancer，Single Arm, Multicenter Phase II Clinical Study

Evaluate the efficacy and safety of PD1 monoclonal antibody combined with mFOLFOX6 neoadjuvant therapy for advanced resectable metastatic colon cancer with enriched pro-inflammatory pan macrophage subpopulations

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colon Cancer
• Intervention / Treatment: Drug: Serplulimab, mFOLFOX6

Detailed Description

In this study, patients with advanced resectable metastatic colon cancer requiring neoadjuvant chemotherapy were selected, and colon cancer patients enriched with TNFSF10+CXCL10+ panTAMs subgroup were screened, and neoadjuvant chemotherapy was performed with PD-1 monoclonal antibody combined with chemotherapy. To evaluate the efficacy and safety of PD-1 monoclonal antibody combined with neoadjuvant chemotherapy in the treatment of special types of colon cancer.

All patients in this study were examined in the tumor microenvironment before treatment, and only patients enriched with TNFSF10+CXCL10+ panTAMs subgroup were enrolled in the study. Due to the long detection time, the patient received mFOLFOX6 chemotherapy for one week in the first cycle. If the test results meet the enriched proinflammatory panmacrophage subpopulation, patients can eventually be enrolled and receive PD-1 monoclonal antibody (Serplulimab, Srulimab) combined with mFOLFOX6 (oxaliplatin, fluorouracil) regimen, 2 weeks for 1 cycle. The primary radical resection was performed after 5 cycles of neoadjuvant therapy. Local treatment of liver/lung metastases was performed at the same time or at different times. Continue mFOLFOX6 chemotherapy for 4-6 cycles or CAPEOX regimen for 4 cycles within 1-2 months after surgery. Liver and lung metastases allow local treatment in any of these treatment cycles, including but not limited to radiofrequency ablation, particle implantation, radiation therapy, and surgery. At the end of postoperative adjuvant therapy, NED status was achieved. Then, regular follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ning Li; Phone Number: 0086-13526501903; Email: lining97@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed the inform consent
• Age >=18 years old, female and male
• Locally advanced or metastatic colorectal adenocarcinoma (including sig-ring cell carcinoma, mucinous adenocarcinoma, etc.) confirmed by pathology (histology or cytology)
• Enriched with proinflammatory panmacrophage subsets
• At least one measurable or evaluable lesion according to RECIST 1.1; Measurable lesions should not have received local treatment such as radiotherapy (Metastases can still be used as target lesions to evaluate efficacy after biopsy. Periintestinal lymph node imaging determines metastasis, allowing for a minimum diameter of ≥ 10mm, and can also be used as target lesions.)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• The life expectancy is ≥6 months；And according to the MDT in the hospital, only neoadjuvant chemotherapy is needed
• Hemoglobin content (HB) ≥ 90g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;Platelet count (PLT) ≥ 100 × 109/L (did not use interleukin-11 or TPO within 14 days);White blood cell count (WBC) ≥ 4.0 × 109/L (no use of granulocyte stimulating factor within 14 days).
• Total serum bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN;Cr ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60ml/min, (Cockcroft Gault formula);Serum albumin ≥ 25 g/L (2.5 g/dL)
• For liver metastasis subjects, AST and ALT must be ≤ 5 x ULN, and white blood cells must be ≥ 4 × 109/L, platelets without blood transfusion ≥ 100 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 without granulocyte stimulating factor treatment × 109/L, hemoglobin ≥ 90 g/L
• Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%).
• Adequate coagulation function, defined as international standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;

Exclusion Criteria:

• Allergy to any investigational drug or its excipients, or a history of severe allergies, or contraindications to investigational drugs;
• Having a history of autoimmune diseases or being in an active phase;
• Symptomatic/Asymptomatic Brain Metastasis
• CT indicates clear ulcerative lesions or fecal occult blood positive for three or more consecutive times, and clinical considerations suggest the presence of gastrointestinal bleeding
• Abnormal thyroid function or taking thyroxine tablets
• Previously received allogeneic bone marrow transplantation or organ transplantation;
• Congenital pulmonary fibrosis, drug-induced pneumonia, organized pneumonia, or CT confirmed active pneumonia;
• HIV positive, active hepatitis B or C, active pulmonary tuberculosis;

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
Experimental: Serplulimab, mFOLFOX6; Serplulimab，200mg，iv，q2w，d1； mFOLFOX6（Oxaliplatin: 85 mg/m2，LV ：400mg/m2，Fluorouracil： 400mg/m2 d1，2400 mg/m2 continuous intravenous drip for 46-48 hours；q2w）	Drug: Serplulimab, mFOLFOX6; Serplulimab，200mg，iv，q2w，d1； mFOLFOX6（Oxaliplatin: 85 mg/m2，LV ：400mg/m2，Fluorouracil： 400mg/m2 d1，2400 mg/m2 continuous intravenous drip for 46-48 hours；q2w）; Other Names: HLX10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic complete response（pCR）	pCR is defined as the percentage of participants in the analysis population who have a pathologic complete response	1 month after resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator.	1 month after resection
2-year overall survival rate	Overall survival is defined as the time from randomization to death due to any cause	2-year
Incidence of Treatment-Emergent Adverse Events	All participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Event,Version 4.0(CTC AE4.0).	up to 6 months

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Suxia Luo, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: January 1, 2024

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: HLX10IIT114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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