A Study of BL-B01D1 in Patients With Multiple Solid Tumors, Including Recurrent or Metastatic Gynecological Malignancies

Phase 1

Recruiting

• Conditions: Solid Tumor; Gynecological Malignant Tumor
• Interventions: Drug: BL-B01D1

• Registration Number: NCT05803018
• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

Brief Summary

Phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy of BL-B01D1 for injection in patients with multiple solid tumors, including recurrent or metastatic gynecological malignancies

Detailed Description

Phase Ib: To explore the safety and initial efficacy of BL-B01D1 in a variety of solid tumors, including recurrent or metastatic gynecological malignancies, to further identify RP2D. To evaluate the initial efficacy of BL-B01D1. The pharmacokinetic characteristics and immunogenicity of BL-B01D1 were further evaluated. Phase II: To explore the efficacy of BL-B01D1 as a single agent RP2D in patients with multiple solid tumors such as recurrent or metastatic gynecological malignancies using Phase Ib clinical studies. To evaluate the safety and tolerance of BL-B01D1. To evaluate the pharmacokinetic characteristics and immunogenicity of BL-B01D1.

Study Timeline

• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-03-26
• Study First Posted: 2023-04-07
• Study Start: 2023-06-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-07
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Sign the informed consent voluntarily and follow the program requirements;

2. Age: ≥18 years old and ≤75 years old;

3. Expected survival time ≥3 months;

4. Recurrent or metastatic gynecological malignancies (including but not limited to ovarian cancer, endometrial cancer, cervical cancer, fallopian tube cancer) and other solid tumors confirmed by histopathology and/or cytology that have failed or been intolerant to standard treatment or currently have no standard treatment; The so-called intolerance refers to grade 3-4 adverse reactions after receiving standard treatment, and the patient refuses to continue the original treatment.

5. Agree to provide archived tumor tissue samples (10 unstained sections (anti-slip) surgical specimens (4-5μm thickness) or fresh tissue samples of primary lesion or metastasis within 3 years. If the subject is unable to provide tumor tissue samples, he/she can be enrolled in the study after evaluation by the investigator under the condition that other inclusion criteria are met;

6. There must be at least one measurable lesion consistent with the RECIST v1.1 definition;

7. Physical condition score ECOG 0 or 1;

8. The toxicity of previous antitumor therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0 (the investigators considered asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated blood glucose, etc., and toxicities without safety risks as determined by the investigators, such as hair loss, grade 2 peripheral neurotoxicity, or decreased hemoglobin but ≥90g/L);

9. No serious cardiac dysfunction, left ventricular ejection fraction ≥50%;

10. The level of organ function must meet the following requirements and meet the following standards:

    1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90 g/L;
    2. Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis;
    3. Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (based on Cockcroft and Gault's formula, see Appendix 5).

11. Coagulation function: International Normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;

12. Pregnancy tests must be performed within 7 days prior to the start of treatment for premenopausal women who are at risk of having children, serum or urine pregnancy tests must be negative and must be non-lactating; All enrolled patients should take adequate barrier contraception throughout the treatment cycle and 6 months after the end of treatment.

Exclusion Criteria

1. Antitumor therapy such as chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigators), and targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks prior to initial administration or within 5 half-lives, whichever is shorter; Mitomycin and nitrosourea were administered within 6 weeks before the first administration; Oral fluorouracil drugs such as Tizio, capecitabine, or palliative radiotherapy within 2 weeks before first administration; The duration of radiotherapy or surgery for brain metastases was 4 weeks.

2. History of severe cardiovascular and cerebrovascular diseases, including but not limited to:

   1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias and degree III atrioventricular block that require clinical intervention;
   2. Prolonged QT interval at rest (QTc > 450 msec in men or 470 msec in women);
   3. Myocardial infarction, unstable angina, angioplasty or stenting, coronary/peripheral artery bypass grafting, class III or Ⅳ congestive heart failure, cerebrovascular accident, or transient ischemic attack within 6 months prior to initial administration;

3. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel diseases, Hashimoto's thyroiditis, etc., except type I diabetes mellitus, hypothyroidism that can be controlled by alternative therapy alone, and skin diseases that do not require systemic treatment (e.g. Vitiligo, psoriasis);

4. There are other malignancies that have progressed or require treatment within 5 years prior to initial administration, with the following exceptions: basal cell carcinoma of the skin after radical treatment, squamous cell carcinoma of the skin, superficial bladder carcinoma, carcinoma in situ after radical resection, such as carcinoma in situ of the breast, and prostate cancer; Remarks: Subjects with localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6, and PSA < 10ng/mL (as measured) at the time of prostate cancer diagnosis were eligible to participate in this study after radical treatment and without biochemical recurrence of prostate-specific antigen (PSA));

5. Patients with interstitial lung disease (ILD) who were defined as ≥3 lung diseases according to CTCAE v5.0;

6. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within the first 6 months of screening; Thrombus formation associated with infusion set is excluded;

7. Patients with central nervous system (CNS) metastasis and/or cancerous meningitis (meningeal metastasis). But have received brain metastases (radiation or surgery; Patients with stable BMS with BMS < 10mm in length and diameter who had stopped radiotherapy and surgery 28 days before the first dose were admitted. Patients with cancerous meningitis (meningeal metastasis) were excluded even after treatment and judged to be stable. The definition of stability should meet the following four requirements:

   1. The seizure-free state persists for > 12 weeks with or without antiepileptic drugs;
   2. Glucocorticoid use is not required;
   3. Two consecutive MRI scans (at least 4 weeks between scans) showed stable imaging status;
   4. Asymptomatic and stable for more than 1 month after treatment;

8. Symptomatic and poorly controlled chest, abdomen and pelvic effusion and pericardial effusion;

9. Patients with a history of allergy to recombinant humanized antibody or mouse chimeric antibody or to any excipients of BL-B01D1;

10. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);

11. Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 103) IU/ml) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of detection) or novel coronavirus infection (novel coronavirus nucleic acid test positive);

12. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;

13. Other conditions deemed unsuitable for participation in this clinical trial by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Study treatment	BL-B01D1	Participants receive BL-B01D1 as intravenous infusion for 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

Name	Time	Method
Phase Ib: 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.
Phase II: Objective response rate (ORR)	Up to approximately 24 months	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
Phase Ib/II: 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.
Phase Ib: Objective response rate (ORR)	Up to approximately 24 months	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Phase Ib/II: Tmax	Up to approximately 24 months	Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated.
Phase II: Progression-free survival (PFS)	Up to approximately 24 months	The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.
Phase Ib/II: Cmax	Up to approximately 24 months	Maximum serum concentration (Cmax) of BL-B01D1 will be investigated.
Phase Ib: T1/2	Up to approximately 24 months	Half-life (T1/2) of BL-B01D1 will be investigated.
Phase Ib/II: Disease control rate (DCR)	Up to approximately 24 months	The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]).
Phase Ib: AUC0-t	Up to approximately 24 months	Blood concentration - Area under time line.
Phase Ib/II: 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.
Phase Ib/II: Duration of response (DOR)	Up to approximately 24 months	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
Phase Ib: CL	Up to approximately 24 months	To study the serum clearance rate of BL-B01D1 per unit time.
Phase Ib/II: Anti-drug antibody (ADA)	Up to approximately 24 months	Frequency and titer of anti-BL-B01D1 antibody (ADA) will be evaluated.

Trial Locations

Locations (1)

Fudan University ShangHai Cancer Center; 🇨🇳 Shanghai, Shanghai, China