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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called BC3195 for people with advanced cancers that haven't responded well to other treatments. Researchers are assessing the safety and tolerability of BC3195 and its potential to shrink tumors. The study consists of two parts: first, determining the right dose, and then evaluating its effectiveness on specific cancers such as breast, lung, and prostate cancer. Individuals with solid tumors that have not responded to previous treatments and who have at least one measurable tumor may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how BC3195 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that BC3195 is likely to be safe for humans?

In a previous study, BC3195, a new treatment for advanced cancer, was tested. Early results show that BC3195 is generally well-tolerated by patients. Researchers checked for any serious side effects that might require stopping the treatment, known as dose-limiting toxicities (DLTs), to find a safe dose for future studies.

As an early-phase study, the main goal is to assess the treatment's safety for people. Some side effects might occur, but researchers closely monitor the study to ensure patient safety. This treatment is still under investigation to understand all possible effects. If you join a trial, doctors will monitor for any side effects and adjust the dose if needed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BC3195 is unique because it is designed to target advanced cancers by potentially inhibiting specific pathways that promote tumor growth, offering a new mechanism of action compared to traditional therapies like chemotherapy or targeted therapies that often focus on broader cancer cell destruction. Unlike standard treatments that can have significant side effects, BC3195 is administered intravenously in a controlled setting, allowing for careful monitoring and dose adjustments based on individual tolerance and effectiveness. Researchers are excited about BC3195 because it may offer a more personalized and potentially more effective treatment option for various difficult-to-treat cancers, including head and neck, esophageal, and non-small cell lung cancers, among others.

What evidence suggests that BC3195 might be an effective treatment for advanced cancer?

Research has shown that BC3195 could be a promising treatment for advanced cancers. BC3195 is an antibody-drug conjugate (ADC), designed to target cancer cells specifically and deliver medicine directly to them, while avoiding healthy cells. It targets a protein called cadherin-3 (CDH3), often found in higher amounts on certain cancer cells. Early studies have demonstrated that BC3195 can shrink tumors in various cancers, such as head and neck, esophageal, and breast cancer. In this trial, participants in Part 1 will receive BC3195 in a dose-escalation format to determine the recommended phase 2 dose (RP2D). In Part 2, participants will receive BC3195 at the RP2D to further evaluate its anti-tumor effects. Initial results from early human studies suggest it may have anti-tumor effects. While more research is needed, these findings offer hope for patients with advanced solid tumors. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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.

I am using effective birth control and will continue for 6 months after the study ends.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-cancer-advanced-5-2024-54e2f

BC3195 for Advanced Cancer · Recruiting Participants for Phase ... This is a phase Ia/Ib, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity ...

2. ctv.veeva.com ctv.veeva.com/study/a-study-to-assess-the-safety-pharmacokinetics-and-antitumor-activity-of-bc3195-in-patients-with-ad

A Study to Assess the Safety, Pharmacokinetics, and ... Expansion cohorts will focus on tumor types that may derive benefit from BC3195 treatment, including head and neck squamous cell carcinoma ( ...

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06548672/

Trial | NCT06548672 Expansion cohorts will focus on tumor types that may derive benefit from BC3195 treatment, including head and neck squamous cell carcinoma (HNSCC), esophageal ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=268d62bf-3880-4ea8-9009-840995237034

BC3195 / Wuxi Biocity BC3195, a novel ADC targeting cadherin-3 (CDH3): Updated results of a first-in-human phase I study in patients with advanced solid malignancies.

5. researchgate.net researchgate.net/publication/381183399_BC3195_a_novel_ADC_targeting_CDH3_Preliminary_results_of_a_first-in-human_phase_I_study_in_patients_with_advanced_solid_malignancies

BC3195, a novel ADC targeting CDH3: Preliminary results ... Request PDF | BC3195, a novel ADC targeting CDH3: Preliminary results of a first-in-human phase I study in patients with advanced solid malignancies.