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A Study of BL-B01D1 + Axitinib Without or With Pembrolizumab in Patients With Locally Advanced or Metastatic Renal Cancer

Phase 2
Not yet recruiting
Conditions
Renal Cancer
Interventions
Registration Number
NCT06962787
Lead Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.
Brief Summary

This Phase II study is a clinical study to explore the efficacy and safety of BL-B01D1 + axitinib without or with pembrolizumab (BL-B01D1 + axitinib ± pembrolizumab) in patients with locally advanced or metastatic renal cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
120
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Study treatmentBL-B01D1Participants receive BL-B01D1+ axitinib ± pembrolizumab in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Study treatmentaxitinibParticipants receive BL-B01D1+ axitinib ± pembrolizumab in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Study treatmentpembrolizumabParticipants receive BL-B01D1+ axitinib ± pembrolizumab in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Primary Outcome Measures
NameTimeMethod
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.

Secondary Outcome Measures
NameTimeMethod
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.

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.

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.

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.

CmaxUp to approximately 24 months

Maximum serum concentration (Cmax) will be investigated.

CtroughUp 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.

Drug-drug Interactions (DDI)Up to approximately 24 months

Drug-drug Interaction (DDI) refers to the pharmacokinetic and pharmacodynamic changes that occur between drugs when multiple drugs are used simultaneously.

Treatment Emergent Adverse Event (TEAE)Up to approximately 24 months

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.

TmaxUp to approximately 24 months

Time to maximum serum concentration (Tmax) will be investigated.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

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