BC3195 for Advanced Cancer

Overseen By Eric Rowinsky, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biocity Biopharmaceutics Co., Ltd.

Must not be taking: Steroids, Immunosuppressants, CYP3A4 drugs

Disqualifiers: Pregnancy, CNS metastases, Hypertension, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

148 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had prior systemic anticancer treatment within 5 half-lives or 4 weeks before the first dose, and you must not be on strong CYP3A4 inhibitors or inducers within 14 days or 5 half-lives before the first dose.

What makes the drug BC3195 unique for advanced cancer treatment?

There is no standard treatment for advanced urothelial cancer, especially for patients who cannot use cisplatin-based chemotherapy. BC3195 may offer a novel option for these patients, potentially providing a new mechanism of action or treatment approach compared to existing therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with advanced or metastatic cancer who have not had success with standard treatments due to disease progression or intolerance. Participants must be able to perform daily activities with minimal assistance.

Inclusion Criteria

Life expectancy ≥ 3 months

My organs are functioning well.

Patients voluntarily participate in the study and should provide a written informed consent

Exclusion Criteria

I am currently on medication for a viral infection.

Pregnant or lactating women

I haven't had cancer treatment or experimental drugs within the last 4 weeks or 5 half-lives, whichever is shorter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BC3195 administered as an intravenous infusion every 3 weeks, monitored for dose limiting toxicities over 21 days

21 days

1 visit every 3 weeks

Dose Expansion

Participants receive BC3195 at the recommended phase 2 dose, focusing on specific tumor types

6 weeks

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• BC3195

Trial Overview The study tests BC3195's safety and effectiveness in two parts: first, finding the right dose (Part 1), then seeing how well it works at that dose (Part 2). Patients will go through screening, treatment, and follow-up periods.

Participant Groups

Group I: Part 2: Phase 1b Dose Expansion Experimental Treatment 1 Intervention

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.

Group II: Part 1: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Biocity Biopharmaceutics Co., Ltd.

Lead Sponsor

Trials

9

Recruited

1,100+

Findings from Research

In a study involving 25 patients with advanced urothelial carcinoma, bortezomib was found to be well tolerated with no treatment-related deaths, but it did not show any objective antitumor responses.

The median survival time for patients treated with bortezomib was 5.7 months, indicating that while the drug is safe, it lacks efficacy as a second-line treatment for advanced urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207. Rosenberg, JE., Halabi, S., Sanford, BL., et al.[2021]

In a study of 960 patients with advanced small cell bladder cancer (aSCBC), the median overall survival was only 8.6 months, with palliative therapy being the most common treatment, especially for those with distant metastases (M1).

When compared to 27,796 patients with urothelial carcinoma (UC), those with aSCBC had worse survival outcomes in cases of lymph node involvement (N+M0), but similar survival rates when both groups had distant metastases (M1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma. Geynisman, DM., Handorf, E., Wong, YN., et al.[2021]

The MAJA study found that vinflunine (VFL) combined with best supportive care (BSC) showed a trend towards improved overall survival (OS) compared to BSC alone in patients with advanced urothelial carcinoma, with median OS of 16.7 months for VFL + BSC versus 13.2 months for BSC alone.

Despite the observed benefits, the study was not sufficiently powered to demonstrate a statistically significant OS advantage, and no unexpected long-term adverse effects were reported, indicating that VFL may be a safe option for maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final Overall Survival Analysis of the SOGUG Phase 2 MAJA Study: Maintenance Vinflunine Versus Best Supportive Care After First-Line Chemotherapy in Advanced Urothelial Carcinoma. Bellmunt Molins, J., García-Donas Jiménez, J., Valderrama, BP., et al.[2021]

In a phase II trial involving 178 patients with advanced urothelial cancer who were unfit for cisplatin-based chemotherapy, the gemcitabine and carboplatin (GC) combination showed a higher overall response rate of 42% compared to 30% for the methotrexate, carboplatin, and vinblastine (M-CAVI) combination.

Severe acute toxicity (SAT) was lower in the GC group (13.6%) compared to the M-CAVI group (23%), indicating that GC may be a safer option for this patient population, although patients with poor performance status (PS 2) and impaired renal function did not show significant benefits from either treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. De Santis, M., Bellmunt, J., Mead, G., et al.[2022]

A study analyzing 10,824 patients with metastatic bladder cancer over two decades revealed a significant decrease in 6-month and 12-month relative survival rates from 67.8% in 1991-2000 to 64.7% in 2001-2010, indicating worsening outcomes for these patients.

The decline in survival rates was particularly notable among Caucasian and other races, while African American patients did not show significant changes, suggesting potential disparities in treatment effectiveness or access to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival trends in metastatic bladder cancer in the United States: a population based study. Shah, BK., Mandal, R.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Final Overall Survival Analysis of the SOGUG Phase 2 MAJA Study: Maintenance Vinflunine Versus Best Supportive Care After First-Line Chemotherapy in Advanced Urothelial Carcinoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Survival trends in metastatic bladder cancer in the United States: a population based study. [2021]