Clinical trial NCT05990803: A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies
Official title: A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 Monotherapy, SI-B003 Monotherapy and BL-B01D1+SI-B003 Combination Therapy (BL-B01D1+SI-B003) in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: Gynecological malignancies
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2023-08-14
Enrollment: 130
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objective: To explore the efficacy, safety and tolerability of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in patients with recurrent or metastatic cervical cancer and other gynecological malignancies, and to further explore the optimal dose and mode of combination.

Detailed description: Objective: To explore the efficacy of BL-B01D1 monotherapy, SI-B003 monotherapy, and BL-B01D1+SI-B003 combination therapy in patients with recurrent or metastatic cervical cancer. To explore the safety and tolerability of BL-B01D1 monotherapy, SI-B003 monotherapy and BL-B01D1+SI-B003 combination therapy in patients with recurrent or metastatic cervical cancer and other gynecological malignancies, and to further explore the optimal dose and mode of combination therapy.

Eligibility criteria: Inclusion Criteria:

1. Subject volunteered to participate in the study and signed an informed consent;
2. Women aged ≥18 years and ≤75 years;
3. Expected survival time ≥3 months;
4. ECOG score 0-1;
5. Gynecological malignancies such as recurrent or metastatic cervical cancer confirmed by histopathology and/or cytology after failure or intolerance to standard treatment or for which no standard treatment is available;
6. Agree to provide 10 surgical specimens or fresh tissue samples of primary or metastatic tumors within 3 years;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
8. No blood transfusion, colony-stimulating factor, any cell growth factor injection, or albumin injection were allowed within 14 days before the first use of the study drug, and the organ function level must meet the requirements;
9. Urine protein ≤2+ or ≤1000g/24h;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
12. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, a serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Prior treatment with an ADC drug with a topoisomerase I inhibitor as a toxin;
2. Use of antineoplastic therapy within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil or palliative radiotherapy within 2 weeks before the first dose;
3. Cohort_B and Cohort_C with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis;
4. Cohort_B, Cohort_C, who had received an immunomodulatory drug within 14 days before the first dose of study drug;
5. Had a history of serious cardiovascular and cerebrovascular diseases;
6. Active autoimmune and inflammatory diseases;
7. Other malignant tumors that progressed or required treatment within 5 years before the first dose;
8. A history of ILD requiring steroid therapy, current ILD, or suspected ILD at screening that could not be ruled out by imaging;
9. History of poorly controlled diabetes mellitus, poorly controlled hypertension, or hypertensive crisis or hypertensive encephalopathy before the first medication;
10. New onset of deep vein thrombosis within 14 days before screening or pulmonary embolism within 6 months;
11. Patients with active central nervous system metastases;
12. Patients with massive, symptomatic, poorly controlled, or unstable effusions;
13. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B01D1's excipients;
14. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
15. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
16. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc;
17. Had participated in another clinical trial within 4 weeks before the first dose;
18. Who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
19. Patients with a history of intestinal obstruction within 6 months before the screening period;
20. Other circumstances that the investigator deemed inappropriate for participation in the trial.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Disease control rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of response (DOR)
timeFrame: Up to approximately 24 months
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Lingying Wu, PHD
role: PRINCIPAL_INVESTIGATOR
References: