Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Colorectal Neoplasms

Microsatellite Instability

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Bone Density Conservation Agents

Vitamins

Antibodies

Antibodies, Monoclonal

Bevacizumab

Irinotecan

Cetuximab

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Immunoglobulins

Calcium, Dietary

Folinic Acid

Subjects receive HX008 200 mg intravenous (IV) every 3 weeks (Q3W)

1. mFOLFOX6
2. mFOLFOX6+Bevacizumab
3. mFOLFOX6+Cetuximab
4. FOLFORI
5. FOLFORI+Bevacizumab
6. FOLFORI+Cetuximab

HX008

Drug: bevacizumab 5mg/kg given by IV every 14 days. Other Name: Avastin

Drug: cetuximab 400 mg/sqm initial dose, then 250 mg/sqm once weekly thereafter. Other Name: Erbitux

Drug: oxaliplatin 8 5 mg/sqm by IV, day1. Component of mFOLFOX6.

Drug: irinotecan 180 mg/sqm by IV, day1.Component of FOLFORI.

Drug: calcium Folinate 400 mg/sqm by IV, day1.Component of mFOLFOX6 or FOLFORI.

Drug: 5-fluorouracil 400 mg/sqm, day1,followed by 2400 mg/sqm iv infusion over 46\~48 h.Component of mFOLFOX6 or FOLFORI.

Investigator's Choice Chemotherapy

Jing Huang

Yifu He

Zhihui Liu

Yuxian Bai

Suxia Luo

Xinjun Liang

Xianli Yin

Qu Xiujuan, PhD

Hui Wang

Enxiao Li

The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), achieved by HX008 or Investigator's Choice Chemotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC).

A Study of HX008 Compared to Chemotherapy in the First-Line Treatment of Subjects With MSI-H/dMMR Metastatic Colorectal Cancer

A Randomized Phase III Study of HX008 (a Humanized Monoclonal Antibody Against PD-1) Compared to Investigator's Choice Chemotherapy in the First-Line Treatment of Subjects With Microsatellite Instability-High (MSI-H)/Deficient DNA Mismatch Repair (dMMR) Metastatic Colorectal Cancer

PFS, defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by IRC or death due to any cause, whichever occurs first.

PFS, defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by investigators or death due to any cause, whichever occurs first.

ORR, defined as the percentage of subjects achieving complete response (CR) and partial response (PR).

DCR, defined as the proportion of subjects achieving CR, PR, and Stable disease(SD) after treatment.

DOR, defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.

OS, defined as the duration from the start of treatment to death of any cause.

iPFS, defined as the time from randomization to the first documented disease immune progression per iRECIST assessed by IRC/investigators or death due to any cause, whichever occurs first.

iORR, defined as the proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

response, a partial response or stable disease according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria by IRC/investigators over the the total number of evaluable patients.

iDOR, defined as the time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

ORR2, defined as proportion of subjects with best overall response of CR or PR, in progressors who continue to receive HX008 in crossover group.

DCR2, defined as the proportion of subjects achieving CR, PR, and SD after treatment who continue to receive HX008 in crossover group.

DOR2, defined as the duration from the initial recording received HX008 in crossover group of objective disease response to the second onset of tumor progression, or death of any cause.

PFS2, defined as duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive).

iORR2, defined as the proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) in progressors who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

iDCR 2, defined as the percentage of patients whose best overall response is either a complete response, a partial response or stable disease who continue to receive HX008 in crossover group according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria by IRC/investigators over the the total number of evaluable patients.

iDOR2, defined as the time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

iPFS2, defined as duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive) who continue to receive HX008 in crossover group based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IRC/investigators.

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, etc.

Spots Global Cancer Trial Database for colorectal neoplasms intestinal neoplasms bevacizumab cetuximab irinotecan oxaliplatin antibodies antibodies monoclonal antine