SHR-8068 Combined With Adbelizumab and BP102 in the Treatment of Advanced Colorectal Cancer

NCT06373133 | Not Yet Recruiting Phase 1

• 1 other identifier: 2024 (82)
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the efficacy and safety of SHR-8068 and Adebrelimab in Combination With Bevacizumabin in the treatment of microsatellite stable (MSS) advanced colorectal cancer.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity

  The dose is considered tolerable if the incidence of DLT is less than 33.3%.

  The first 21 days of the first cycle of medication

• PFS

  Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment.

  Up to 2 years

Study Arms (1)

SHR-8068+Adebrelimab+BP102

EXPERIMENTAL

The first 9 subjects will be treated with low dose SHR-8068 (1mg/kg, q6w), and the subsequent subjects will be treated with high dose SHR-8068 (4mg/kg, q12w) if the toxicity of DLT is tolerable during the observation period.

Drug: SHR-8068; Drug: Adebrelimab; Drug: BP102

Interventions

SHR-8068 DRUG

1mg/kg，ivgtt, d1, q6w or 4mg/kg，ivgtt, d1, q12w

Also known as: Anti-CTLA4 monoclonal antibody

SHR-8068+Adebrelimab+BP102

Adebrelimab DRUG

1200mg, ivgtt, d1, q3w

Also known as: SHR-1316

SHR-8068+Adebrelimab+BP102

BP102 DRUG

7.5mg/kg, ivgtt, d1, q3w

Also known as: Bevacizumab

SHR-8068+Adebrelimab+BP102

Eligibility Criteria

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

You may qualify if:

• pathologically confirmed metastatic colorectal adenocarcinoma;
• Age of 18-75 years old, both sexes;
• predicted survival time ≥12 weeks;
• Eastern Cooperative Oncology Group performance status (ECOG) score 0-2;
• Participants who had failed second-line or higher standard-of-care systemic therapy and should have been treated with oxaliplatin, irinotecan, and fluorouracil were allowed to enroll if first-line therapy included three agents;
• liver tumor burden ≤50% as assessed by enhanced CT or MRI;
• There were no serious complications (perforation, obstruction, massive bleeding, etc.) in the primary lesion;
• According to RECIST1.1 criteria, there should be at least one measurable objective tumor lesion, the maximum diameter of which must be ≥1cm by spiral CT, and the maximum diameter of which must be ≥2cm by conventional CT or MRI; This procedure was performed within 28 days before enrollment.
• Study participants had to have adequate organ function, as assessed by the following laboratory results within 1 week before enrollment (no blood transfusion, granulocyte colony-stimulating factor, or other medical support within 14 days before study drug administration) :
• Blood routine examination: hemoglobin ≥90g/L; Platelet (PLT) ≥75×109/L; White blood cell (WBC) ≥3.0×109/L; Neutrophil (ANC) ≥1.5×109/L;
• Blood biochemical examination: total bilirubin (TBI) ≤1.5× upper limit of normal (UNL); Serum creatinine (Cr) ≤1.5× upper limit of normal; Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤5×UNL;
• study participants with active hepatitis B or active hepatitis C, who must have received antiviral therapy for at least 14 days before the first dose of the study drug, If they have a hepatitis B virus (HBV) DNA titer test (not higher than 500 IU/mL or 2500 copies \[cps\]/mL) and a hepatitis C virus (HCV) RNA test (not higher than the lower limit of detection of the assay), can be enrolled in the trial, and are willing to continue to receive effective antiviral therapy during the study;
• Patients volunteered to participate and provided written informed consent.

You may not qualify if:

• a history of other malignancies with disease-free survival \<5 years (except cured basal cell carcinoma of the skin, cured carcinoma in situ of the cervix, and gastrointestinal cancer proven cured by endoscopic mucosal resection);
• participated in other drug clinical trials within four weeks;
• patients with known CNS metastases or a history of CNS metastases before screening. For patients with clinically suspected central nervous system metastasis, contrast-enhanced CT or contrast-enhanced magnetic resonance imaging (MRI) was required within 28 days before informed consent to rule out central nervous system metastasis.
• patients with a long history of chronic diarrhea or complete intestinal obstruction;
• urinalysis showed urinary protein ≥2+ or 24-hour urinary protein ≥1g;
• Drug-uncontrolled hypertension (systolic blood pressure \> 140 MMHG or diastolic blood pressure \> 90mmHg);
• a history of severe bleeding (\> 30ml per episode) within 3 months or hemoptysis (\> 5ml per episode) within 1 month or thromboembolic events (including pulmonary embolism, cerebral infarction, etc.) within 12 months;
• had undergone surgical treatment (excluding biopsy) within 6 weeks or had unhealed surgical incisions;
• long-term unhealed wounds or incompletely healed fractures;
• imaging shows that the tumor has invaded the vital blood vessels or the patient's tumor has a high possibility of invading the vital blood vessels during treatment, which may cause fatal bleeding;
• with a history of unstable angina pectoris; Newly diagnosed angina pectoris within 3 months before screening or myocardial infarction within 6 months before screening; Arrhythmias (including QTcF ≥450 ms in men and ≥470 ms in women) required long-term use of antiarrhythmic drugs and New York Heart Association (NYHA) grade ≥II cardiac dysfunction.
• patients with abnormal coagulation function and bleeding tendency (INR within the normal range without anticoagulant therapy must be met within 14 days before the first medication); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; Low-dose warfarin (1 mg orally once daily) or low-dose aspirin (at a dose of up to 100 mg daily) for preventive purposes were allowed if the International Normalized Ratio of prothrombin time (INR) was 1.5 or less.
• participants with an active or prior autoimmune disease or risk (e.g., organ transplant requiring immunosuppressive therapy) that may relapse. However, participants with type 1 diabetes, hypothyroidism for which they were receiving hormone-replacement therapy only, or skin conditions for which no systemic treatment was required (e.g., vitiligo, psoriasis, or alopecia) were allowed.
• have had a history of interstitial lung disease or noninfectious pneumonia, such as symptomatic disease or a previous pulmonary history that may preclude assessment or management of study-drug-related pulmonary toxicity;
• Participants with a history of active pulmonary tuberculosis infection within 1 year before the first dose of the study drug and a history of active pulmonary tuberculosis infection more than 1 year before were considered eligible if they had no evidence of current active pulmonary tuberculosis, as assessed by the investigator;

Sponsors & Collaborators

• West China Hospital: lead

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 18, 2024

Record last verified: 2024-04