An Open Label, Multi-cohort, Multicenter Phase II Study to Evaluate the Efficacy and Safety of Envofolimab in Combination With BD0801 Injection With/Without Chemotherapy in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 2
- Intervention
- Envofolimab
- Conditions
- Advanced Solid Tumor
- Sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- Enrollment
- 86
- Locations
- 24
- Primary Endpoint
- Part I: MTD（Maximum tolerable dose）or RD（Recommended dose）
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open label, multi-cohort, multicenter Phase II study, the purpose of this study is to assess the efficacy and safety of envofolimab in combination with BD0801 injection with/without chemotherapy for the treatment of advanced solid tumors
Detailed Description
The efficacy of immune checkpoint inhibitors combined with antivascular agents has been preliminarily demonstrated in a variety of solid tumors. Based on the huge clinical needs, the efficacy of envofolimab combined with BD0801 in patients with advanced hepatocellular carcinoma, non-small cell lung cancer and advanced colorectal cancer deserves further exploration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients voluntarily signed informed consent;
- •Age≥18 age years old, male or female;
- •Patients diagnosed with unresectable or advanced solid tumors confirmed by histopathology or cytology; Cohort A: Patients must have progressed on standard of therapy, patients with NSCLC, CRC and HCC (include intrahepatic cholangiocarcinoma or mixed hepatocellular carcinoma-cholangiocarcinoma in safety run-in phase) are enrolled preferentially; Cohort B: Patients with histopathologically or cytologically or clinically diagnosed advanced HCC (Barcelona Clinic Liver Cancer (BCLC) Stage C; or BCLC Stage B patients who are not suitable for locoregional therapy (such as TACE) may also be enrolled), Child-Pugh liver function grade A and patients received at least one standard first-line systemic treatment and no more than 3 systemic regimens for HCC; Cohort C: Histologically confirmed NSCLC (except for patients with central and cavernous lung squamous cell carcinoma). Patients received at least one standard first line systemic treatment are required, if patients with EGFR、ALK or ROS1 gene positive, first line of target therapy will be required ( if patients with known EGFR mutation, they should be T790M negative or with osimertinib treatment failure); C1: Required prior anti-PD-1/PD-L1 therapy. C2: Never used prior anti-PD-1/PD-L1 therapy. Cohort D: Patients with advanced CRC confirmed with histology, the results of tissue samples must meet any of the following (
- •the test result of immunohistochemistry is mismatch repair protein integrity (pMMR)
- •the test result of NGS is MSI-L or MSS 3 the test of result of PCR is MSI-L or MSS). Has received the oxaliplatin and 5-Fu containing regimen for the treatment of metastatic tumors.
- •ECOG score 0 or 1;
- •At least one measurable lesion as per RECIST V1.1;
- •Normal major organ and marrow functions as defined and no blood transfusion and blood product within 2 weeks before screening, no use of hematopoietic stimulating factors;
- •Life expectancy≥12 weeks;
- •Women of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first dose. Male or female patients of childbearing potential voluntarily use effective contraceptive methods from signing the informed consent form to 6 months after initiation of the study drug, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients are considered to be of childbearing potential unless they are postmenopausal (continuous menopause for 12 month), had undergone artificial menopause, or had undergone surgical sterilization (e.g., hysterectomy, surgical adnexectomy);
Exclusion Criteria
- •Patients who have participated in clinical trials of other investigational drugs or investigational devices within 28 days prior to the first dose or received any systemic treatments within 2 weeks, include but not limited chemotherapy, radiotherapy (palliative radiotherapy is allowed at least 1 week before the study drug treatment), targeted therapy, Chinese herbal medicine or proprietary Chinese medicine for cancer control;
- •Patients with a history of Envofolimab or BD0801 treatment;
- •Patients who have ascites requiring drainage or diuretic treatment or pleural effusion or pericardial effusion requiring drainage and/or accompanied by shortness of breath within 2 weeks before the first dose of study drug treatment;
- •Cholangiocarcinoma, mixed cell carcinoma, or fibroblastic layer cell carcinoma are known for Cohort B;
- •Patients with other active malignancies within 2 years prior to the first administration of the study drug randomization, curable localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, and carcinoma in situ of the breast can be included in the group;
- •Patients whose toxicity and side effects (due to previous anticancer treatments) have not recovered to≤grade 1, unless such AE is not considered to pose safety risks (such as hair loss and neuropathy≤grade 2 caused by oxaliplatin)
- •Patients with previous and current central nervous system (CNS)metastasis;
- •Patients with a history of hepatic encephalopathy;
- •Patients with active tuberculosis (TB), who are receiving anti-TB treatment or received anti-TB treatment within 3 months prior the first study drug administration;
- •Abdominal fistula, gastrointestinal perforation, abdominal abscess and intestinal obstruction with clinical symptoms (including occlusive disease);
Arms & Interventions
A: Solid tumor
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）
Intervention: Envofolimab
D：NSCLC
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）+Docetaxel(75mg/m2，Q3W)
Intervention: Envofolimab
A: Solid tumor
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）
Intervention: BD0801
B: HCC
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）
Intervention: Envofolimab
B: HCC
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）
Intervention: BD0801
D：NSCLC
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）+Docetaxel(75mg/m2，Q3W)
Intervention: BD0801
D：NSCLC
Envofolimab（300mg，Q3W）+BD0801（2mg/kg，Q3W）+Docetaxel(75mg/m2，Q3W)
Intervention: Docetaxel
D：CRC
Envofolimab（200mg，Q2W）+BD0801（2mg/kg，Q2W）+FOLFIRI（Irinotecan 180 mg/m2，Leucovorin 400mg/m2，5-Fluorouridine 2400 mg/m2，Q2W）
Intervention: Envofolimab
D：CRC
Envofolimab（200mg，Q2W）+BD0801（2mg/kg，Q2W）+FOLFIRI（Irinotecan 180 mg/m2，Leucovorin 400mg/m2，5-Fluorouridine 2400 mg/m2，Q2W）
Intervention: Irinotecan
D：CRC
Envofolimab（200mg，Q2W）+BD0801（2mg/kg，Q2W）+FOLFIRI（Irinotecan 180 mg/m2，Leucovorin 400mg/m2，5-Fluorouridine 2400 mg/m2，Q2W）
Intervention: Leucovorin calcium
D：CRC
Envofolimab（200mg，Q2W）+BD0801（2mg/kg，Q2W）+FOLFIRI（Irinotecan 180 mg/m2，Leucovorin 400mg/m2，5-Fluorouridine 2400 mg/m2，Q2W）
Intervention: 5-Fluorouridine
Outcomes
Primary Outcomes
Part I: MTD（Maximum tolerable dose）or RD（Recommended dose）
Time Frame: 6 months
MTD: A maximum dose of acceptable safety, at least 6 patients treated with this dose, and less than 1/3 of patients experienced DLT(Dose limited toxicity). RD:The following will be taken into account to make decision about RD: MTD, if is reached; PK characteristics, efficacy and safety results.
Part II: ORR(Objective Response Rate ) by investigator
Time Frame: 1.5 years
Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria
Secondary Outcomes
- PFS(Progression Free Survival) by investigator(1.5 years)
- ORR in subgroup of different TMB、PDL-1 and MSI status(1.5 years)
- OS（Overall Survival)(2.5 years)
- The incidence of AEs（adverse events) and SAEs（serious adverse events)(2 years)
- DOR(Duration Of Response) by investigator(1.5 years)
- DCR(Disease Control Rate) by investigator(1.5 years)