A Clinical Study to Evaluate Efficacy and Safety of Serplulimab（HLX10） Combined With Bevacizumab（HLX04) and Chemotherapy (XELOX) in Patients With Metastatic Colorectal Cancer (mCRC)

NCT04547166 | Recruiting Phase 2

• 1 other identifier: HLX10-015-CRC301
• Study Type: interventional
• Target: 568
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a two-arm, randomized, double-blinded, multicenter phase III clinical study to evaluate the clinical efficacy of Serplulimab (HLX10) in Combination With Bevacizumab and Chemotherapy (XELOX) Versus Placebo in Combination With Bevacizumab and Chemotherapy (XELOX) in First-line Treatment of Patients With Metastatic Colorectal Cancer (mCRC)

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival (assessed by independent radiological review committee (IRRC) based on RECIST v1.1)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (6)

• OS

  From date of randomization until the date of first date of death from any cause, assessed up to 100 months

• PFS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• ORR

  through study completion, an average of 1 year

• Duration of response

  from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed up to 2 years

• DCR

  the proportion of patients with the best overall response of CR, PR, or stable disease (SD) persisting for 12 weeks

Study Arms (2)

Serplulima +Bevacizumab+XELOX

EXPERIMENTAL

Serplulimab (HLX10) in Combination With Bevacizumab and chemotherapy (XELOX)

Drug: HLX10; Drug: HLX04、

placebo + Bevacizumab+XELOX

PLACEBO COMPARATOR

placebo in combination with Bevacizumab and chemotherapy (XELOX)

Drug: HLX04、

Interventions

HLX10 DRUG

a single fixed dose of 300 mg, intravenous infusion (IV), every 3 weeks (Day 1 of each cycle \[D1\]), non-reducible.

Also known as: serplulimab

Serplulima +Bevacizumab+XELOX

HLX04、 DRUG

7.5mg/kg, IV, every 3 weeks (D1 of each cycle), non-reducible.

Also known as: Bevacizumab

Serplulima +Bevacizumab+XELOX; placebo + Bevacizumab+XELOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed unresectable metastatic/recurrent colorectal adenocarcinoma
• Life expectancy ≥ 12 weeks
• Have not received any previous systemic anti-tumor drug treatment for metastatic colorectal adenocarcinoma
• For participants who have previously received neoadjuvant/adjuvant therapy, the time from the last treatment to recurrence or progression must exceed 12 months.
• With at least one measurable lesion as assessed by the IRRC per RECIST v1.1, and the measurable lesion should not have been treated locally such as with radiotherapy (a lesion located in an area subjected to previous radiotherapy can also be regarded as a measurable lesion if PD is confirmed)
• Agree to provide sufficient previously preserved tumor tissue specimens or agree to undergo biopsy to collect tumor tissue for some gene test.
• Have an ECOG PS score of 0 or 1 within 7 days prior to receiving the first dose of the study drugs
• Have Adequate major organ functions.

You may not qualify if:

• Have confirmed MSI-H CRC (gene test)
• Subjects with oligometastatic liver disease and presenting the potential for becoming resectable
• Presence of central nervous system (CNS) or leptomeningeal metastases
• Have received radiotherapy within 6 months prior to the initiation of study treatment, except for palliative radiotherapy for bone disorders at least 14 days prior to initiation of study treatment; radiotherapy covering more than 30% of the bone marrow area within 28 days prior to randomization is not allowed.
• With a history of or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severe pulmonary dysfunction, or any condition that may interfere with the detection and management of suspected drug-related pulmonary toxicity
• Have received major surgery within 28 days prior to randomization. A major surgery in this study is defined as a surgery requiring at least 3 weeks of recovery to be able to receive the treatment in this study
• Previously received intestinal stent implantation, with the stent remaining in place at the screening period
• Uncontrolled hypertension despite clinical treatment (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg)
• With a history of hypertensive crisis or hypertensive encephalopathy
• With a history of significant/severe hemorrhage within 1 month prior to randomization, or have received blood transfusion within 2 weeks prior to randomization
• Requiring long-term treatment with daily administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Occasional use of NSAIDs to relieve medical symptoms such as headache or pyrexia is allowed
• With evidence showing the presence of meteorism that cannot be attributed to puncture or recent surgery
• Presence of severe, unhealed or split wounds and active ulcers or untreated fractures
• Presence of any of the following medical conditions within 6 months prior to randomization:
• Abdominal or tracheoesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, massive ascites as judged by the investigator (defined as patients requiring drainage or treatment within two weeks)

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (5)

Center for Cancer Prevention and Treatment of Sun Yat-sen University

Guangzhou, Guangdong, 510075, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

Linyi Cancer Hospital

Linyi, China

RECRUITING

Fudan University Affiliated Oncology Hospital

Shanghai, China

RECRUITING

National Cancer Center

Kashiwa, Japan

NOT YET RECRUITING

Related Publications (1)

• Wang ZX, Peng J, Liang X, Cheng Y, Deng Y, Chen K, Zhang M, Zhang J, Wang W, Cao B, Jin Y, Sun M, Lin Y, Luo S, Li Z, Yang L, Ke Y, Yu H, Li J, Wang Q, Zhu J, Wang F, Xu RH. First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial. Med. 2024 Sep 13;5(9):1150-1163.e3. doi: 10.1016/j.medj.2024.05.009. Epub 2024 Jun 12.

  PMID: 38870931 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ruihua Xu

  Center for Cancer Prevention and Treatment of Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Ruihua Xu

CONTACT

020-87343292; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 14, 2020
• Study Start: March 10, 2021
• Primary Completion: September 24, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: October 17, 2024

Record last verified: 2024-10

Locations

CN (4); JP (1)