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This is a phase Ia/Ib, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BC3195 in subjects with locally advanced or metastatic solid tumors in whom standard treatment has failed (either due to disease progression or intolerance). This study will consist of two parts: Dose escalation (Part 1) and dose expansion (Part 2). Each part will include a screening period, a treatment period, and follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Phase 1a Dose Escalation | Experimental | Participants will receive BC3195 administered as an intravenous infusion every 3 weeks (Q3W) or according to an alternative dosing regimen, as recommended by the safety monitoring committee (SMC). Multiple dose cohorts will be enrolled. Participants will be monitored for dose limiting toxicities (DLTs) during the DLT assessment period, lasting 21 days. The SMC will determine the recommended phase 2 dose (RP2D) to be administered in Part 2 based on the safety, tolerability, PK, and anti-tumor activity of BC3195 |
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| Part 2: Phase 1b Dose Expansion | Experimental | Participants will receive BC3195 at the RP2D identified in Phase 1a. Approximately 3 to 4 expansion cohorts will be enrolled using a Simon's 2-stage design. Expansion cohorts will focus on tumor types that may derive benefit from BC3195 treatment, including head and neck squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), non-small cell lung cancer (NSCLC), endometrial cancer (EMC), urothelial cancer (UC), colorectal cancer (CRC), ovarian cancer (OC), pancreatic cancer, and prostate cancer. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BC3195 | Drug | BC3195 is a novel antibody drug conjugate (ADC) targeting CDH3 (calcium-dependent adhesion 3). The payload, monomethyl auristatin E (MMAE), is a microtubule disrupting agent covalently attached to the antibody via a cleavable dipeptide linker Val-Cit (vc). |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) | First 21 days of treatment | |
| Determination of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) | Day 1 of treatment through 30 days after the last dose | |
| Incidence and Severity of All Adverse Events (AEs) | Screening through 12 weeks after the last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 | Day 1 of treatment through 6 weeks after the last dose |
| Disease Control Rate (DCR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eric Rowinsky, MD | Contact | 908-883-0647 | erowinsky@oncodrugs.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Case Western Reserve University | Recruiting | Cleveland | Ohio | 44106 | United States |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Proportion of subjects with CR, PR, and stable disease (SD)
| Day 1 of treatment through 6 weeks after the last dose |
| Duration of Response (DoR) | Defined as the time from the date when the measurement criteria were met for complete or partial response (whichever occurred first) until the date of the first observed PD or death of any cause | Day 1 of treatment through 6 weeks after the last dose |
| Time to Progression (TTP) | Defined as the length of time from the start of treatment until first evidence of disease progression | Day 1 of treatment through 6 weeks after the last dose |
| Progression Free Survival (PFS) | Defined as the time from which the subject is enrolled to the date of any recorded disease progression or the death of any cause | Day 1 of treatment through 6 weeks after the last dose |
| Overall Survival (OS) | Defined as the time from Day 1 of dosing until the date of death from any cause assessed up to 100 months | Patient consent until death Day 1 of dosing until the date of death from any cause assessed up to 100 months |
| Area under the curve (AUC) of BC3195 | Area under the BC3195 time vs concentration curve | Day 1 of dosing through 21 days post last dose |
| Maximum concentration (Cmax) of BC3195 | Maximum concentration observed following dosing | Day 1 of dosing through 21 days post last dose |
| Time to reach maximum concentration (Tmax) of BC3195 | Time at which the maximum concentration of BC3195 is observed | Day 1 of dosing through 21 days post last dose |
| Half-life (t 1/2) of BC3195 | Time at which BC3195 concentration is reduced by one half | Day 1 of dosing through 21 days post last dose |
| Volume of distribution (Vd) of BC3195 | Volume of distribution | Day 1 of dosing through 21 days post last dose |
| Clearance (CL) of BC3195 | Volume of drug cleared in a period of time | Day 1 of dosing through 21 days post last dose |
| Immunogenicity indicators | Anti-drug antibody (ADA) | Day 1 of dosing through 30 days post last dose |