Advanced Cancer, Metastatic Solid Tumor
Conditions
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.
Interventions
DRUGBC3195
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).
Sponsors
Biocity Biopharmaceutics Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ≥ 18 years of age. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 3. 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. 4. 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) 5. 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 6. Life expectancy ≥ 3 months 7. Subjects with adequate organ function 8. 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. 9. Patients voluntarily participate in the study and should provide a written informed consent.
Exclusion criteria
1. Pregnant or lactating women 2. Prior systemic anticancer treatment, including investigational agents, within 5 half-lives or 4 weeks before the first dose (whichever is shorter) 3. 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 4. Previously received allogeneic tissue/solid organ transplantation 5. Patients who have received radiation therapy within 2 weeks prior to the start of study treatment or with a history of radiation pneumonitis. 6. 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 7. Active viral infection requiring systemic therapy during the screening period 8. Clinically uncontrolled pericardial effusion, pleural effusion, or ascites at screening 9. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease 10. 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 \[with at least 2- minute interval between each measurement\]) 11. 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 12. 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 13. Grade 2 or higher peripheral neuropathy. Other toxicities caused by prior anti-tumor therapy has not recovered to ≤ grade 1 (per CTCAE 5.0) (except for alopecia, pigmentation, and other events judged by the Investigator to be tolerable) or the level specified by the inclusion/
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | Day 1 of treatment through 6 weeks after the last dose | Defined as the length of time from the start of treatment until first evidence of disease progression |
| Progression Free Survival (PFS) | Day 1 of treatment through 6 weeks after the last dose | Defined as the time from which the subject is enrolled to the date of any recorded disease progression or the death of any cause |
| Overall Survival (OS) | Patient consent until death Day 1 of dosing until the date of death from any cause assessed up to 100 months | Defined as the time from Day 1 of dosing until the date of death from any cause assessed up to 100 months |
| Area under the curve (AUC) of BC3195 | Day 1 of dosing through 21 days post last dose | Area under the BC3195 time vs concentration curve |
| Maximum concentration (Cmax) of BC3195 | Day 1 of dosing through 21 days post last dose | Maximum concentration observed following dosing |
| Disease Control Rate (DCR) | Day 1 of treatment through 6 weeks after the last dose | Proportion of subjects with CR, PR, and stable disease (SD) |
| Half-life (t 1/2) of BC3195 | Day 1 of dosing through 21 days post last dose | Time at which BC3195 concentration is reduced by one half |
| Volume of distribution (Vd) of BC3195 | Day 1 of dosing through 21 days post last dose | Volume of distribution |
| Clearance (CL) of BC3195 | Day 1 of dosing through 21 days post last dose | Volume of drug cleared in a period of time |
| Immunogenicity indicators | Day 1 of dosing through 30 days post last dose | Anti-drug antibody (ADA) |
| Time to reach maximum concentration (Tmax) of BC3195 | Day 1 of dosing through 21 days post last dose | Time at which the maximum concentration of BC3195 is observed |
| Objective Response Rate (ORR) | Day 1 of treatment through 6 weeks after the last dose | Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 |
| Duration of Response (DoR) | Day 1 of treatment through 6 weeks after the last dose | 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 |
Countries
United States
Contacts
Primary ContactEric Rowinsky, MD
Outcome results
None listed