A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of BC3195 in Patients With Advanced or Metastatic Cancer

NCT06548672 | Recruiting Phase 1 FDA Drug

• 1 other identifier: BC3195-102
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cancer; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (13)

• Objective Response Rate (ORR)

  Day 1 of treatment through 6 weeks after the last dose

• Disease Control Rate (DCR)

  Day 1 of treatment through 6 weeks after the last dose

• Duration of Response (DoR)

  Day 1 of treatment through 6 weeks after the last dose

• Time to Progression (TTP)

  Day 1 of treatment through 6 weeks after the last dose

• Progression Free Survival (PFS)

  Day 1 of treatment through 6 weeks after the last dose

Study Arms (2)

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

Drug: BC3195

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.

Drug: BC3195

Interventions

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).

Part 1: Phase 1a Dose Escalation; Part 2: Phase 1b Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Subjects with locally advanced or metastatic solid tumors confirmed by histology or cytology who have not benefitted from or are intolerant of available therapy(ies) associated with a reasonable likelihood to confer clinical benefit because of known CDH3 expression, including, albeit not limited to: HNSCC, ESCC, BC, NSCLC, EC, UC, CRC, OC, pancreatic cancer, and prostate cancer.
• Agree to provide previously archived tumor tissue samples, or newly obtained core biopsy, or excisional biopsy of a previously unirradiated tumor lesion (formalin fixed, paraffin embedded tissue blocks)
• Subjects with at least one measurable lesion according to RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Life expectancy ≥ 3 months
• Subjects with adequate organ function
• Men or women of childbearing potential must use a highly effective method of contraception during the study and continue to take contraception measures for 6 months after the last dose of the study drug.
• Patients voluntarily participate in the study and should provide a written informed consent.

You may not qualify if:

• Pregnant or lactating women
• Prior systemic anticancer treatment, including investigational agents, within 5 half-lives or 4 weeks before the first dose (whichever is shorter)
• Subjects diagnosed with immunodeficiency within 7 days prior to the first dose of the study drug; or subjects who are receiving longterm systemic steroid therapy or any other form of immunosuppressive therapy
• Previously received allogeneic tissue/solid organ transplantation
• Patients who have received radiation therapy within 2 weeks prior to the start of study treatment or with a history of radiation pneumonitis.
• Known active CNS metastases and/or cancerous meningitis. Subjects with previously treated brain metastases who meet the following conditions are permitted to participate in the study: radiologically stable, that is, repeat imaging shows no evidence of progression for at least 4 weeks, clinically stable, and no steroid therapy is required for at least 14 days prior to the first dose of study treatment
• Active viral infection requiring systemic therapy during the screening period
• Clinically uncontrolled pericardial effusion, pleural effusion, or ascites at screening
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Hypertension that cannot be well-controlled with medical treatment. Not well-controlled is defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg (adjustment of hypertensive medication prior to study initiation is permitted, but the mean of the most recent three consecutive blood pressure records prior to study entry must be ≤150/90 mmHg \[with at least 2- minute interval between each measurement\])
• Cardiovascular disease of clinical significance: Including New York Heart Association \[NYHA\] Class II-IV, congestive heart failure, second-degree or higher heart block, myocardial infarction within the past 3 months, unstable arrhythmia or unstable angina, marked QT interval prolongation (12-lead ECG showing baseline-corrected QTc interval \>480 ms), cerebral infarction within 3 months, or having received PTCA or CABG within 6 months
• Subjects with active or chronic corneal disorders, with other active ocular conditions requiring ongoing therapy or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy
• Subjects with any active infection that requires anti-infective therapy judged by the investigators
• Known hypersensitivity or delayed hypersensitivity reactions to the same class and/or any components of BC3195
• Subjects who received strong CYP3A4 inhibitors and Strong CYP3A4 inducers within 14 days or 5 half-lives whichever is shorter, before the first dose (refer to Appendix 7 for a list of strong CYP3A4 inhibitors and inducers)

Sponsors & Collaborators

• Biocity Biopharmaceutics Co., Ltd.: lead

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Eric Rowinsky, MD

CONTACT

908-883-0647; erowinsky@oncodrugs.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: August 12, 2024
• Study Start: June 24, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)