A Phase IIa Study to Investigate the Efficacy and Safety of BRY812 for Injection in Patients With LIV-1 Positive Advanced Gynecologic Malignancies
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 56
- Primary Endpoint
- Efficacy assessment (RECIST v1.1)
Overview
Brief Summary
This study is a single-arm, open-label, multicenter Phase IIa trial designed to evaluate the efficacy, safety, and pharmacokinetic profile of BRY812 for Injection in patients with LIV-1-positive advanced gynecological malignancies. The study comprises two cohorts. For Cohort 1 (ovarian cancer), a Simon's two-stage design is adopted. In the first stage, 13 evaluable subjects will be enrolled. If fewer than 3 subjects achieve an objective response among these 13, enrollment in this cohort will be terminated. Otherwise, the cohort will proceed to the second stage, and additional 23 evaluable subjects will be enrolled, bringing the total to 36. If at least 10 out of the 36 evaluable subjects achieve an objective response, the cohort will be considered worthy of further investigation. Cohort 2 (endometrial cancer and ovarian clear cell carcinoma) plans to enroll approximately 20 subjects in a single stage.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •(1) Subjects who voluntarily sign the informed consent form, understand the nature, objectives, and procedure of the study and are able to complete the study according to the protocol;
- •(2) Female patients, ≥ 18 years of age (based on the date of signing the informed consent form);
- •(3) LIV-1 positive, as assessed by a central laboratory
- •(4) Patients with histologically or cytologically confirmed locally advanced or metastatic gynecological malignancies are enrolled into two cohorts:
- •Cohort 1 (Ovarian Cancer):
- •Diagnosis of high-grade serous epithelial ovarian cancer (EOC). Must have received 1 to 3 prior lines of systemic anticancer therapy.
- •Cohort 2 (Endometrial Cancer and Ovarian Clear Cell Carcinoma):
- •For Endometrial Cancer: Diagnosis of recurrent or metastatic advanced endometrial carcinoma (all histologies except sarcoma). Patients must have received up to 3 prior lines of systemic therapy, platinum-based chemotherapy and anti-PD-1/PD-L1 therapy .
- •For Ovarian Clear Cell Carcinoma: Pathologically confirmed ovarian clear cell carcinoma. The definitions for prior therapy lines (1-3 lines) are the same as for Cohort
- •(5) According to RECIST v1.1 (Response Evaluation Criteria in Solid Tumors), there is at least 1 measurable lesion;
Exclusion Criteria
- •(1) Subjects who have previous severe hypersensitivity to BRY812 or known hypersensitivity to any component or excipient of the study drug;
- •(2) Subjects who have previously received drugs which target LIV-1, or MMAE-containing drugs, including but not limited to antibody-drug conjugates (ADCs) that utilize MMAE as the cytotoxic payload;
- •(3) Subjects who have any active infection requiring systemic therapy by intravenous infusion within 2 weeks prior to the first dose of study drug;
- •(4) Subjects who have previous or current presence of two or more primary tumors (excluding cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin, and other tumors that have been stable for more than 5 years after treatment);
- •(5) Subjects who have symptoms of active central nervous system metastases, except those with brain parenchymal metastases assessed as stable by the investigator based on the following conditions:
- •No seizures within \> 12 consecutive weeks with or without the treatment of antiepileptic drugs;
- •Glucocorticoids are not required within the 2 weeks prior to the first dose;
- •Two consecutive MRI scans (at least 4 weeks apart) show a stable state on imaging;
- •The conditions remain stable and asymptomatic for more than 1 month after treatment;
- •(6) Subjects with serious cardiovascular and cerebrovascular diseases and lung diseases, including but not limited to:
Arms & Interventions
BRY812
Intervention: BRY812 for injection (Drug)
Outcomes
Primary Outcomes
Efficacy assessment (RECIST v1.1)
Time Frame: Baseline, every 6 weeks after first dose up to 24 weeks, every 12 weeks thereafter, through study completion, an average of 6 months
The Objective Response Rate (ORR) and other efficacy outcomes will be evaluated by an Independent Review Committee (IRC) using RECIST 1.1 criteria
Secondary Outcomes
- Immunogenicity assessment(Immediately after the intervention, through study completion, an average of 6 months)
- Safety assessment (NCI CTCAE v5.0)(Immediately after the intervention, through study completion, an average of 6 months)
- Pharmacokinetic assessment(Immediately after the intervention, through study completion, an average of 6 months)