QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer

NCT04527068 | Unknown Phase 2

• 1 other identifier: BEVTOR202008
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm,open-label, prospective, single-center Study of QL1101 and JS001 in patients with pMMR/MSS refractory metastatic colorectal cancer. QL1101 is a biosimilar of bevacizumab (Avastin) produced and provided by Qilu Pharmaceutical Co., Ltd., which has been marketed in China.It's a humanized monoclonal IgG1 antibody prepared by recombinant DNA technology. By binding to human vascular endothelial growth factor (VEGF), it inhibits the binding of VEGF to its receptor, blocks the signal transduction pathway of angiogenesis, and inhibits tumor cell growth. Be produced and provided by Shanghai Junshi Bioscience Co., Ltd. ,JS001(Tripleitriumab) is the first China-developed humanized monoclonal antibody against programmed death 1 (PD-1) approved for marketing in China. Antiangiogenic drugs combined with PD-1 monoclonal antibodies may reverse the insensitivity of pMMR/MSS refractory colorectal cancer to PD-1 inhibitors. The primary objective of this study is to investigate the safety and efficacy of the subjects who given the combination therapy.

Conditions

Refractory Metastatic Colorectal Cancer; pMMR; MSS

Keywords

metastatic colorectal cancer; refractory; QL1101; JS001; tripleitriumab; bevacizumab; pMMR; MSS; immunotherapy; PD-1; VEGF; antiangiogenic; mCRC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. PFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%.

  From the first use of research drugs to documented disease progression per RECIST 1.1 and iRECIST or death from any cause, whichever occurs first, assessed up to 18 months

Secondary Outcomes (4)

• Overall survival (OS)

  From the first use of research drugs to death from any cause, assessed up to 18 months

• Overall response rate(ORR)

  up to 18 months

• Disease Control Rate (DCR)

  up to 18 months

• Duration of Response (DOR)

  From the date of first tumor assessment with the response status being CR or PR to the date of 1st documented progressive disease, assessed up to 12 months

Study Arms (1)

Bevacizumab +Tripleitriumab

EXPERIMENTAL

Participants receive bevacizumab 7.5mg/kg and tripleitriumab 240mg in day 1 intravenously every 3week until disease progression or unacceptable toxicity

Drug: Bevacizumab; Drug: Tripleitriumab

Interventions

Bevacizumab DRUG

7.5 mg/kg intravenously every 3week

Also known as: QL1101

Bevacizumab +Tripleitriumab

Tripleitriumab DRUG

240mg intravenously every 3week

Also known as: JS001

Bevacizumab +Tripleitriumab

Eligibility Criteria

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

You may qualify if:

• Patients with unresectable advanced (metastatic or locally advanced) colorectal cancer confirmed by histology or cytology
• The results of tissue samples or liquid biopsy measured by the pathology department or laboratory department of a tertiary hospital and a qualified genetic testing company meet any of the following:
• The test result of immunohistochemistry is mismatch repair protein integrity (pMMR)
• The test result of NGS or liquid biopsy + NGS is MSI-L or MSS
• The test result of PCR is MSI-L or MSS
• Previous treatment must meet all of the following conditions:
• Thymidylate synthase inhibitors,such as 5-FU, capecitabine, UFT,raltitrexed,Tegafur,Gimeracil and Oteracil Porassium Capsules,have been accepted for disease metastasis or as adjuvant therapy. Thymidylate synthase inhibitors can be combined with oxaliplatin or irinotecan
• Have received the irinotecan-containing regimen (single or combination) for the treatment of metastatic tumors and the treatment has failed, or has a record of unsuitable irinotecan-containing regimen treatment
• Failure is defined as disease progression (clinical or radiological) or intolerance to irinotecan-containing regimens. Intolerance is defined as discontinuation of use due to any of the following reasons: severe allergic reaction or delayed recovery from toxicity, which prevents retreatment
• Recorded conditions that are not suitable for irinotecan treatment include (but are not limited to) known hypersensitivity to irinotecan, abnormal glucuronidation of bilirubin, Gilbert syndrome, or received pelvic or abdominal radiation therapy.
• Has received the oxaliplatin-containing regimen (single or combination) for the treatment of metastatic tumors and the treatment has failed, or recurred within 6 months after completion of oxaliplatin-containing adjuvant therapy,or has a record of unsuitable oxaliplatin-containing regimen treatment
• Failure is defined as disease progression (clinical or radiological) or intolerance to oxaliplatin-containing regimens, where intolerance is defined as discontinuation of use due to any of the following reasons: severe allergic reaction, persistent severe neurotoxicity or delayed recovery of toxicity prevents retreatmen
• Recorded conditions that are not suitable for treatment with oxaliplatin-containing regimens include but are not limited to known hypersensitivity to oxaliplatin or other platinum compounds, renal insufficiency, or sensory neuropathy of grade ≥2
• For patients with RAS wild type colorectal cancer: patients who have received cetuximab or panizumab regimens (monotherapy or combination) for tumor metastasis and failed, or have been recorded to be unsuitable for treatment with cetuximab or panizumab regimens
• Failure is defined as disease progression (clinical or radiological) or intolerance to cetuximab or panizumab therapy, where intolerance is defined as discontinuation of use due to any of the following reasons: severe infusion reaction, delayed recovery of persistent skin toxicity or toxicity, preventing retreatment

You may not qualify if:

• Have received any systemic chemotherapy within 28 days before the first study drug, or have received immunotherapy (such as interleukin, interferon, thymosin), hormone therapy, targeted therapy, or any research therapy within 14 days or 5 half-lives before the first study drug, whichever is the shorter, but immune checkpoint inhibitors are allowed to be pretreated
• Received any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days prior to the use of the drug for the first study
• Patients with primary malignancies other than bowel cancer within 5 years before randomization, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection,ductal carcinoma in situ after radical resection,and papillary thyroid cancer
• Patients whose toxicity and side effects (due to previous anticancer treatments) have not returned to baseline or stable levels, unless such AE is not considered to pose safety risks (such as hair loss, neuropathy and abnormal results of specific laboratory tests)
• Uncontrolled hypertension after treatment (systolic blood pressure ≥ 140mmHg and / or diastolic blood pressure ≥ 90mmHg). Have a history of hypertensive crisis or hypertensive encephalopathy
• Any unstable systemic diseases: including but not limited to cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc. within 6 months before screening), deep vein thrombosis, cardiogenic chest pain (moderate pain in the 28 days before screening leads to instrumental limitation of activities of daily living), myocardial infarction (within 6 months before screening), coronary angioplasty or history of stent placement (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade III within 6 months before screening), symptomatic pulmonary embolism (within 28 days before screening) ), ventricular arrhythmia events with severity ≥ 2 (within 6 months before screening), syncope, seizures or falls (within 28 days before screening), poorly controlled diabetes or poorly controlled electrolyte disorders
• Clinically significant third space effusion (such as a large amount of pleural effusion, ascites, pericardial effusion that cannot be controlled by pumping or other treatments)
• Symptomatic central nervous system metastasis; patients with asymptomatic brain metastasis or stable symptoms after brain metastasis can participate in this study as long as they meet all the following criteria: there are measurable lesions outside the central nervous system; no midbrain, pons, cerebellum, medulla oblongata or spinal cord metastasis; no previous history of intracranial hemorrhage
• The following medical history within 6 months before screening: peptic ulcer, gastrointestinal perforation, corrosive esophagitis or gastritis, inflammatory bowel disease or diverticulitis, abdominal fistula, or intra-abdominal abscess
• Patients with tracheo-esophageal fistula
• Patients with partial or complete bowel obstruction
• Untreated patients with chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA \> 500IU/mL (or the lower limit of detection) and patients with hepatitis C virus (HCV) RNA positive should be excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBVDNA \<500IU/mL or the lower limit of detection) and cured hepatitis C patients can be selected
• Human immunodeficiency virus (HIV) antibodies or syphilis testing positive
• Severe chronic or active infections (according to CTCAE version 5.0, ≥ grade 3) require systemic antibacterial, antifungal or antiviral treatment, including tuberculosis j infections. Patients with a history of active tuberculosis infection ≥ 1 year before screening should also be excluded, unless proof can be provided that appropriate treatment has been completed
• Patients with Child - Pugh B or more severe liver cirrhosis

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

the Second Affiliated Hospital of Medical College of Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

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

• Ying Yuan, M.D.

  The Second Affiliated Hospital of Medical College of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanguang Hu, M.D.

CONTACT

+86-13858110651; huhanguang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2020
• First Posted: August 26, 2020
• Study Start: September 20, 2020
• Primary Completion: September 1, 2021
• Study Completion: February 1, 2022
• Last Updated: September 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)