YL211 for Cancer

Recruiting at 12 trial locations

Overseen By Sasha Stann

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.

Disqualifiers: Cardiovascular, Pulmonary, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

155 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, open-label, Phase 1 study. The study will enroll subjects with advanced solid tumors. It consists of three parts. Part 1 is dose-escalation part. In part 1, the safety and tolerability of YL211 in patients with selected advanced solid tumors will be evaluated and the MTD and RED will be determined. Part 2 is backfill enrollment part. We will further estimate the safety and efficacy of YL211 in patients with selected adcance tumor to select the RED(s) of YL211. Part 3 is dose-expansion part. In this part, we will further evaluate the safety and efficacy of YL211 at the MTD/RED(s) in patients with selected advanced solid tumors YL211 will be administered intravenously (IV) until criteria of treatment discontinuation are met.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions an 'inadequate washout period' for prior anticancer treatment as an exclusion criterion. This suggests that you may need to stop certain anticancer treatments before starting the trial.

What makes the drug YL211 unique for cancer treatment?

YL211 is unique because it involves the forced expression of the YL-1 protein, which acts as a transformation suppressor by reducing the ability of cancer cells to grow independently, a key feature of cancer progression. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with advanced solid tumors who have likely tried other treatments without success. Specific details about eligibility criteria are not provided, but typically participants must be adults in stable condition and able to comply with study requirements.

Inclusion Criteria

Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF

Be able and willing to comply with protocol visits and procedures

Have at least 1 extracranial measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Exclusion Criteria

I haven't had a long enough break from my last cancer treatment before starting the study drug.

I have a serious lung condition besides my cancer.

I still have side effects from past cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Safety and tolerability of YL211 are evaluated to determine the maximum tolerated dose (MTD) and recommended expansion dose (RED)

Approximately 12 months

Backfill Enrollment

Further estimation of safety and efficacy of YL211 to select the RED(s)

Approximately 12 months

Dose-Expansion

Evaluation of safety and efficacy of YL211 at the MTD/RED(s) in patients with advanced solid tumors

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• YL211

Trial Overview YL211 is being tested in this Phase I trial. It's given intravenously to patients with advanced solid tumors across three parts: dose-escalation to find the maximum tolerated dose (MTD), backfill enrollment to confirm safety and efficacy, and dose-expansion at MTD to further assess its effects.

Participant Groups

Group I: Part 3: Dose-Expansion Part Experimental Treatment 1 Intervention

Dose-Expansion Part

Group II: Part 2: Backfill Enrollment Part Experimental Treatment 1 Intervention

Backfill Enrollment Part

Group III: Part 1: Dose-Escalation Part Experimental Treatment 1 Intervention

Dose-Escalation Part

Who Is Running the Clinical Trial?

MediLink Therapeutics (Suzhou) Co., Ltd.

Lead Sponsor

Trials

12

Recruited

3,400+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

The YL-1 gene product significantly suppresses anchorage-independent growth in Kirsten sarcoma virus-transformed NIH3T3 cells, indicating its role as a transformation suppressor.

While YL-1 effectively inhibits colony formation in soft agar, it does not affect other transformed characteristics in adherent cultures or tumorigenicity in nude mice, suggesting its specific action on anchorage independence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Forced expression of YL-1 protein suppresses the anchorage-independent growth of Kirsten sarcoma virus-transformed NIH3T3 cells. Horikawa, I., Tanaka, H., Yuasa, Y., et al.[2009]

Cytoplasmic Y-box-binding protein 1 (YB1) is linked to more aggressive breast cancer characteristics, such as higher nuclear grade and the presence of breast cancer stem cells, indicating a potential role in tumor progression.

Nuclear YB1 expression is associated with poorer disease-free survival in breast cancer patients, particularly those receiving chemotherapy and radiotherapy, suggesting it could be a prognostic marker for recurrence risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse. Mylona, E., Melissaris, S., Giannopoulou, I., et al.[2016]

Y box-binding protein 1 (YB-1) levels are significantly higher in breast cancer tissues and certain breast cancer cell lines compared to normal breast tissues, suggesting its role in breast cancer proliferation.

Manipulating YB-1 levels in SK-BR-3 breast cancer cells shows that reducing YB-1 decreases cell proliferation, while increasing YB-1 promotes it, indicating that YB-1 may be a potential target for breast cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation]. Shi, J., Lü, X., Wang, B., et al.[2018]

YY1 can effectively suppress the growth of various tumor cell types, including human breast carcinoma and glioblastoma cells, as demonstrated in vitro.

In a rat model, YY1 reduced the growth of mammary adenocarcinoma tumors by approximately 80% over 21 days, indicating its potential as a therapeutic agent against certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. Ishii, H., Hulett, MD., Li, JM., et al.[2012]

Y-box binding protein-1 (YB-1) is linked to poor prognosis in breast cancer by promoting the expression of cancer stem cell markers CD44 and CD49f, which enhances cancer cell growth and drug resistance.

Targeting YB-1 can sensitize breast cancer cells, particularly those with high CD44 and low CD24 expression, to the chemotherapy drug paclitaxel, suggesting a potential therapeutic strategy to overcome drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. To, K., Fotovati, A., Reipas, KM., et al.[2022]

References

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

Forced expression of YL-1 protein suppresses the anchorage-independent growth of Kirsten sarcoma virus-transformed NIH3T3 cells. [2009]

2. England pubmed.ncbi.nlm.nih.gov

Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse. [2016]

3. China pubmed.ncbi.nlm.nih.gov

[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation]. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. [2012]

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

Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. [2022]