Renal Cancer
Conditions
Brief summary
This Phase II study is a clinical study to explore the efficacy and safety of BL-B01D1 in combination with tyrosine kinase inhibitor (TKI) with or without pembrolizumab (BL-B01D1+TKI±Pembrolizumab) in patients with locally advanced or metastatic renal cancer.
Interventions
DRUGBL-B01D1
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGAxitinib
Oral administration, and twice daily with an interval of 12 hours.
DRUGLenvatinib
Oral administration, and once daily.
DRUGPembrolizumab
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject volunteered to participate in the study and signed an informed consent; 2. Male or female aged ≥18 years and ≤75 years; 3. Expected survival time ≥3 months; 4. ECOG score 0 or 1; 5. Patients with locally advanced or metastatic renal cell carcinoma confirmed by histopathology and/or cytology; 6. Agree to provide archived tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years; 7. At least one measurable lesion meeting the RECIST v1.1 definition was required; 8. Organ function level must meet the requirements; 9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0; 10. Fertile female subjects, or male subjects with fertile partners, must use highly effective contraception from 7 days before the first dose until 7 months after the first dose. Female subjects of childbearing potential had to have a negative serum pregnancy test within 7 days before the first dose.
Exclusion criteria
1. Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil; 2. Prior treatment with an ADC drug containing a camptothecin derivative (topoisomerase I inhibitor) as a toxin; 3. Use of immunomodulatory drugs within 14 days before the first dose of study drug; 4. The history of severe cardiovascular and cerebrovascular diseases within six months before screening; 5. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia; 6. Active autoimmune and inflammatory diseases; 7. Systemic corticosteroids or immunosuppressive agents are required within 2 weeks before the first dose; 8. Other malignant tumors within 5 years before the first dose; 9. A history of non-infectious ILD requiring steroid treatment, or current ILD/interstitial pneumonia or suspected ILD; 10. Poorly controlled diabetes before starting study treatment; Severe complications of diabetes mellitus; 11. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; 12. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment; 13. Patients with active central nervous system metastasis; 14. Patients with massive or symptomatic effusions or poorly controlled effusions; 15. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to BL-B01D1 or any excipients of pembrolizumab; 16. Previous history of allogeneic stem cell, bone marrow or organ transplantation; 17. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection; 18. Had a serious infection within 4 weeks before the first dose of study drug; There was pulmonary infection or active pulmonary inflammation at the time of screening; 19. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose); 20. With a history of psychotropic drug abuse and inability to quit or a history of severe neurological or psychiatric illness; 21. Imaging examination showed that the tumor had invaded or wrapped the large thoracic vessels; 22. Serious unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent; 23. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent; 24. Subjects scheduled to receive live vaccine or within 28 days before the first dose; 25. Patients with other serious physical and laboratory abnormalities or poor compliance that may increase the risk of participating in the study, or interfere with the results of the study, and patients who were deemed by the investigators to be unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 24 months | Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS). |
| Recommended Phase II Dose (RP2D) | Up to approximately 24 months | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B01D1. |
| Frequency of Treatment Emergent Adverse Event (TEAE) | Up to approximately 24 months | Frequency of TEAE will be investigated. TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to approximately 24 months | Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) will be investigated. |
| Duration of Response (DOR) | Up to approximately 24 months | Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-B01D1 antibody (ADA) will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) will be investigated. |
| Overall survival (OS) | Up to approximately 24 months | Overall survival (OS) is defined as the time between the subject's randomization date and subject's death. |
| Progression-free survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects are randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed