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This is a single-arm, multicenter, Phase II clinical study aiming to explore the efficacy and safety of Sacituzumab Govitecan combined with Bevacizumab as a second-line or later treatment for patients with metastatic triple-negative breast cancer (mTNBC). The study will be conducted in 6-8 centers in China.
The study is divided into two phases: a Safety Run-in Phase and a Dose Expansion Phase.
In the Safety Run-in Phase (3-12 patients), three dose levels are planned to determine the recommended dose. The starting dose (Level 1) is Sacituzumab Govitecan 10 mg/kg (Days 1, 8) plus Bevacizumab 7.5 mg/kg (Day 1) every 21 days. Based on the occurrence of Dose-Limiting Toxicities (DLT) in the first cycle, the Safety Monitoring Committee (SMC) will decide whether to continue the current dose or de-escalate to Level 2 (Sacituzumab Govitecan 10 mg/kg + Bevacizumab 5 mg/kg) or Level 3 (Sacituzumab Govitecan 7.5 mg/kg + Bevacizumab 5 mg/kg).
In the Dose Expansion Phase, 40-50 patients will be enrolled to receive the combination therapy at the recommended dose determined in the run-in phase. Efficacy will be evaluated every 2 cycles according to RECIST 1.1, and safety will be assessed continuously until disease progression or intolerable toxicity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sacituzumab Govitecan + Bevacizumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sacituzumab Govitecan (SG) | Drug | Administered via intravenous infusion on Day 1 and Day 8 of each 21-day cycle. In the Safety Run-in phase, the starting dose is 10 mg/kg, with a potential de-escalation to 7.5 mg/kg based on Dose-Limiting Toxicity (DLT). In the Expansion phase, patients receive the determined recommended dose |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival | From start of treatment until disease progression or death, assessed up to approximately 32 months (based on study completion date of Dec 2026) | |
| Incidence and Severity of Adverse Events (Safety) | From start of treatment through 90 days after the last dose of study drug. |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate | From start of treatment until disease progression or intolerance, assessed every 2 cycles, assessed up to approximately 32 months | |
| Overall Survival | From start of treatment until death, assessed up to approximately 32 months |
| Measure | Description | Time Frame |
|---|---|---|
| Trop-2 Expression Level | Assessment of Trop-2 expression in tumor tissue using Immunohistochemistry (IHC). Results are reported as Histochemical Score (H-score, ranging from 0 to 300). This measure will be analyzed to explore the association with efficacy outcomes (PFS, ORR). | From baseline up to approximately 32 months |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital, Chinese Academy of Medical Sciences | Beijing | Beijing Municipality | China |
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| ID | Term |
|---|---|
| C000608132 | sacituzumab govitecan |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Bevacizumab | Drug | Administered by intravenous infusion on the first day of each 21-day cycle. In the safety trial phase, the starting dose is 7.5 mg/kg and can be reduced to 5 mg/kg depending on dose-limiting toxicity (DLT). During the expansion phase, patients receive the determined recommended dose |
|
| Disease Control Rate | From start of treatment until disease progression or intolerance, assessed up to approximately 32 months |
| Duration of Response | From date of first response until disease progression or death,assessed up to approximately 32 months |
| 6-month Progression-Free Survival Rate | At 6 months after treatment initiation |
| 6-month Overall Survival Rate | At 6 months after treatment initiation |
| UGT1A1 Genotype Status |
Assessment of UGT1A1 gene polymorphisms (e.g., 1, 28 alleles) in blood or tissue samples using PCR or sequencing. Results are categorized by genotype (e.g., homozygous wild-type, heterozygous, homozygous mutant). This measure will be analyzed to explore the association with safety outcomes (adverse events). |
| From baseline up to approximately 32 months |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |