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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Investigator's Choice Chemotherapy; Drug: HX008(Pucotenlimab)

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical University
    • Fuyang, Anhui, China
      • The Fifth Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • Anhui Provincial Cancer Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Peking University Cancer Hospital
    • Beijing, Beijing Municipality, China
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing Municipality, China
      • Peking University First Hospital
    • Beijing, Beijing Municipality, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Friendship Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • Gansu Provincial People's Hospital
  • Guangdong
    • Foshan, Guangdong, China
      • The Eighth Affiliated Hospital of Southern Medical University
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • The Sixth Affiliated Hospital, Sun Yat-sen University
    • Meizhou, Guangdong, China
      • Meizhou People's Hospital(Huangtang Hospital)
    • Shantou, Guangdong, China
      • The First Affiliated Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China
      • Guangxi Medical University Affiliated Tumor Hospital
  • Guizhou
    • Guiyang, Guizhou, China
      • Guizhou Provincial People's Hospital
  • Henan
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science and Technology
    • Nanchangcun, Henan, China
      • The Second People's Hospital of nayang City
    • Nanyang, Henan, China
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China
      • Wuhan Central Hospital
  • Hunan
    • Changde, Hunan, China
      • Changde First People's Hospital
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Huaian, Jiangsu, China
      • Huai'an first people's hospital
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Jiangsu Cancer Hospital
    • Nantong, Jiangsu, China
      • Affiliated Qidong Hospital of Nantong University
    • Suzhou, Jiangsu, China
      • Suzhou Ninth People's Hospotal
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • First Affiliated Hospital of Gannan Medical University
    • Ganzhou, Jiangxi, China
      • Ganzhou Municipal Hospital
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • China-Japan Union Hospital of Jilin University
  • Liaoning
    • Fushun, Liaoning, China
      • Liaoning Health Industry Group Fukuang General Hospital
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • General Hospital of the Northern Theater Command of the Chinese People's Liberation Army
  • Shangdong
    • Jinan, Shangdong, China
      • Qilu Hospital of Shandong University
    • Jinan, Shangdong, China
      • Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China
      • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Datong, Shanxi, China
      • The Fifth People's Hospital Of Datong
    • Taiyuan, Shanxi, China
      • First Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China
      • Shanxi Provincial Cancer Hospital
  • Shenyang
    • Dalian, Shenyang, China
      • Dalian University of Technology Affiliated Central Hospital (Dalian Central Hospital)
  • Sichuan
    • Chengdu, Sichuan, China
      • The First Affiliated Hospital of Chengdu Medical College
    • Chengdu, Sichuan, China
      • Chengdu Hospital of Integrated Traditional Chinese and Western Medicine
    • Deyang, Sichuan, China
      • Deyang People's Hospital
    • Mianyang, Sichuan, China
      • Mianyang Central Hospital
    • Nanchong, Sichuan, China
      • North Sichuan Medical College Affiliated Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Tianjin People's Hospital
  • Xi'an
    • Xi'an, Xi'an, China
      • The First Affiliated Hospital of Xi'an Jiaotong University
    • Xi'an, Xi'an, China
      • Second Affiliated Hospital of Xi'an JiaoTong University
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • Affiliated Cancer Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • The Second Affiliated Hospital of Kunming Medical University
    • Kunming, Yunnan, China
      • The First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • Second Affiliated Hospital of Zhejiang University School of Medicine
    • Ningbo, Zhejiang, China
      • Ningbo NO.2 Hospital
    • Quzhou, Zhejiang, China
      • The Affiliated Quzhou Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign the Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
2. Male or female, age ≥ 18 years on the day of signing the informed consent form;
3. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum, classified as Stage IV according to the AJCC (8th edition, 2017) TNM staging system for colorectal cancer;
4. Confirmed MSI-H/dMMR status by the central laboratory;
5. No prior systemic treatment for metastatic colorectal cancer; subjects received neoadjuvant/adjuvant therapy with disease progression should be completed > 6 months prior to the neoadjuvant/adjuvant therapy were enrolled.
6. Has at least one measurable extracranial lesion (Lesions with the longest diameter ≥ 10mm, or lymph nodes with a short diameter ≥ 15mm) according to Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST1.1), which has not been treated with local treatment(Lesions located in the area of previous radiation therapy can also optional if the progression is confirmed);
7. Eastern Cooperative Oncology Group (ECOG) of 0 or 1;
8. Estimated life expectancy of ≥12 weeks;

9. Adequate organ and hematopoietic function (no blood transfusion within 14 days prior to hematology tests, and no use of any hematopoietic growth factors or/and thrombopoietic agents within 7 days), based on the following laboratory tests (retesting is allowed only once during the screening period. If the retest results meet the inclusion criteria, the baseline values will be based on the retest results.):

   1. Absolute neutrophil count (ANC)≥1.5×10^9/L
   2. White blood cell count (WBC)≥3×10^9/L
   3. Platelet count (PLT)≥100×10^9/ L
   4. Hemoglobin (HGB)≥90 g/L
   5. Serum creatinine (Scr) ≤1.5×ULN
   6. Alanine aminotransferase (ALT) 、Aspartate aminotransferase (AST) ≤2.5× (upper limit of normal, ULN) . Patients with liver metastases require ALT and AST≤5×ULN,
   7. TBIL≤1.5×ULN
   8. International normalized ratio (INR) ≤ 2×ULN; or activated partial thromboplastin time (APTT)≤ 1.5×ULN;(except for patients on anticoagulant therapy);
10. Women of childbearing age must have a negative pregnancy test within 72 hours before the first dose of trial treatment. Reproductive men and women of childbearing age are willing to take adequate contraceptive measures (such as oral contraceptives, intrauterine contraceptives, sexual abstinence, or barrier contraceptives combined with spermicide) from signing the informed consent form to 12 months after the last administration of the trial drug;
11. Participants must have good compliance.

Exclusion Criteria:

1. Prior systemic treatment for metastatic colorectal cancer (subjects who received neoadjuvant/adjuvant therapy with disease progression should be completed > 6 months prior to the neoadjuvant/adjuvant therapy were enrolled.)
2. Subjects diagnosed with any other malignancy within 5 years prior to randomization, except for malignancies with a low risk of metastasis and death (5-year survival rate > 90%), such as adequately basal cell or squamous cell skin cancer or carcinoma in situ of the cervix and other carcinomas in situ;
3. Had prior treatment with any anti-PD-1, anti-PD-L1, PD-L2, or CTLA-4 agent or any other drug targeting T cell co-stimulation or immune checkpoint pathway;
4. Has active autoimmune disease (except for psoriasis), that has required systemic treatment in the past 2 years((eg, corticosteroids or immunosuppressive drugs). Except for alternative therapies (eg, thyroxine, insulin or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency);

5. Need to receive systemic corticosteroids (dose equivalent to > 10 mg prednisone/day) or other immunosuppressive drugs within 14 days before enrollment or during the study period. Those under the following conditions are eligible:

   1. Locally external use or inhaled corticosteroids;
   2. short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of nonautoimmune allergic diseases;
6. Has had prior radiation therapy or has not recovered (≤ Grade 1 or at Baseline) from Adverse events(AEs) due to a previous radiation therapy;
7. Has received a significant surgery, open biopsy, or severe trauma within 4 weeks prior to randomization; Definition of major surgery: the minimum of 3 weeks of post-operative recovery time is required to undergo this study, any wound-related AE must be resolved prior to randomization;
8. Has severe infection within 4 weeks or active infection requiring IV infusion or oral administration of antibiotics within 2 weeks prior to randomization;
9. Treatment with investigational products or devices from other clinical trials within 4 weeks prior to randomization;
10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or found during screening;
11. Has uncontrolled ascites requiring repeated drainage, pleural effusion, or pericardial effusion;
12. Has incomplete intestinal obstruction, active gastrointestinal hemorrhage, or perforation;
13. Has a history or current interstitial pneumonia, or current non--infectious pneumonitis treatment with corticosteroids
14. Participants with inadequately controlled cardiovascular diseases judged by the investigator as unsuitable for participation in this trial, including but not limited to: (1) NYHA Class II or above cardiac function, (2) Angina unstable;
15. Subjects with active tuberculosis;
16. History of human immunodeficiency virus infection, acquired or congenital immunodeficiency disease, organ transplantation, or stem cell transplantation;
17. Active chronic hepatitis B or active hepatitis C. Except for hepatitis B virus carriers or those with stable disease after drug treatment, and participants with HBV DNA titer ≤ 500 IU/mL or < 2500 copies/mL are eligible. Active hepatitis C is defined as known positive hepatitis C antibody with known hepatitis C RNA quantitative results above the lower limit of detection of the analytical method;
18. Known to be allergic to macromolecular protein agents or monoclonal antibodies. Known to have a history of severe allergies to any of the chemotherapy drugs in the study ;
19. Alcohol dependence or drug abuse within the past 1 year;
20. Has received a live vaccine within 30 days prior to the first dose of trial treatment. Subjects are permitted to receive inactivated vaccines including those for seasonal influenza, intranasal influenza vaccines are not allowed;
21. Presence of other serious physical or mental illness or abnormal laboratory tests that may increase the risk of subjects in the study, or interfere with the study results, and the researchers believe that patients who are not suitable to participate in the trial for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Investigator's Choice Chemotherapy; mFOLFOX6; mFOLFOX6+Bevacizumab; mFOLFOX6+Cetuximab; FOLFORI; FOLFORI+Bevacizumab; FOLFORI+Cetuximab; CAPEOX; CAPEOX+ Bevacizumab	Drug: Investigator's Choice Chemotherapy; Drug: bevacizumab 5mg/kg given by IV every 14 days. Other Name: Avastin Drug: cetuximab 400 mg/m2 for the first dose, then 250 mg/sqm, intravenous infusion, repeated weekly; or Cetuximab 500 mg/ sqm, intravenous infusion, D1, repeated every 2 weeks. Other Name: Erbitux Drug: oxaliplatin 85 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. Drug: oxaliplatin 130 mg/sqm, intravenous infusion over 2 h ± 30 min, Day 1. Component of CAPEOX. Drug: capecitabine 1000 mg/sqm administered orally twice daily, Days 1-14. Component of CAPEOX. Drug: bevacizumab 7.5 mg/kg, intravenous infusion, D1, repeated every 3 weeks
Experimental: HX008(Pucotenlimab); Subjects receive HX008 200 mg intravenous (IV) every 3 weeks (Q3W)	Drug: HX008(Pucotenlimab); Drug: HX008(Pucotenlimab) 200 mg ,Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Independent Review Committee(IRC)	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life assessment		2 years
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigators	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.	2 years
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by IRC or investigators	ORR, defined as the percentage of subjects achieving complete response (CR) and partial response (PR).	2 years
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by IRC or investigators	DCR, defined as the proportion of subjects achieving CR, PR, and Stable disease(SD) after treatment.	2 years
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by IRC or investigators	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.	2 years
Overall Survival (OS)	OS, defined as the duration from the start of treatment to death of any cause.	2 years
Immune Progression-free Survival (iPFS)-Experimental group per iRECIST assessed by IRC/investigators	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.	2 years
Immune Objective Response Rate (iORR)-Experimental group per iRECIST assessed by IRC/investigators	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.	2 years
Immune Disease Control Rate (iDCR) -Experimental group per iRECIST assessed 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.	2 years
Immune Duration of Response (iDOR)-Experimental group per iRECIST assessed by IRC/investigators	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.	2 years
Objective tumor response rate 2 (ORR2) (crossover phase) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by 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.	2 years
Disease Control Rate 2 (DCR 2) (crossover phase) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by investigators	DCR2, defined as the proportion of subjects achieving CR, PR, and SD after treatment who continue to receive HX008 in crossover group.	2 years
Duration of Response 2 (DOR2) (crossover phase) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by investigators	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.	2 years
Progression-free Survival 2 (PFS2) per Response Evaluation Criteria in Solid Tumors	PFS2, defined as duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive).	2 years
Immune Objective Response Rate 2 (iORR2) (crossover phase) per iRECIST assessed by investigators	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 investigators.	2 years
Immune Disease Control Rate 2 (iDCR2) (crossover phase) per iRECIST assessed by 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 investigators over the the total number of evaluable patients.	2 years
Immune Duration of Response 2 (iDOR2) (crossover phase) per iRECIST assessed by investigators	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 investigators.	2 years
Immune Progression-free Survival 2 (iPFS2) (crossover phase) per iRECIST assessed by 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 investigators.	2 years
Safety: AEs, laboratory test parameters, etc.		2 years

Collaborators and Investigators

• Sponsor: Taizhou Hanzhong biomedical co. LTD

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 20, 2028

Study Registration Dates

• First Submitted: November 26, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal Neoplasms Intestinal Neoplasms Bevacizumab Cetuximab Irinotecan Oxaliplatin Antibodies Antibodies Monoclonal Antine
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: HX008-III-CRC-01

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