YL202 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.

Must be taking: EGFR TKI

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Cardiovascular disease, Brain metastases, ILD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called YL202 to see if it is safe for patients with certain types of advanced lung and breast cancers that haven't responded to other treatments. The drug aims to target specific changes in the cancer cells to stop or slow their growth.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for prior anticancer treatments before starting the study drug. It's best to discuss your current medications with the study team to understand any necessary adjustments.

What makes the drug YL202 (BNT326) unique for cancer treatment?

YL202 (BNT326) is unique because it targets the Mcl-1 protein, which is often overexpressed in certain cancers and helps them resist other treatments. By focusing on Mcl-1, YL202 may overcome resistance seen with other therapies that target different Bcl-2 family proteins. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, or hormone receptor-positive and HER2-negative breast cancer. Participants must have progressed after standard treatments, be able to use effective contraception, and not participate in other clinical studies. Major surgery within the last 4 weeks or need for systemic steroids disqualifies them.

Inclusion Criteria

Informed of the trial before the start of the trial and voluntarily sign their name and date on the informed consent form

I agree to use effective birth control and not donate eggs or sperm during and 6 months after the study.

My organs and bone marrow are working well.

Exclusion Criteria

I haven't had any cancer other than non-melanoma skin cancer or in situ disease in the past 3 years.

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

I have not had major surgery in the last 4 weeks and do not expect any during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive YL202 intravenously in a dose escalation format to evaluate safety and tolerability

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• YL202

Trial Overview YL202 is being tested in this phase 1 study on patients who have heavily treated NSCLC or breast cancer. The goal is to assess its safety and how well it's tolerated when given to individuals whose cancers are either locally advanced or have spread beyond their original site.

Participant Groups

Group I: YL202 Dose escalation Experimental Treatment 1 Intervention

YL202 will be administrated intravenously (IV) per dose level in which the patients are assigned.

Who Is Running the Clinical Trial?

MediLink Therapeutics (Suzhou) Co., Ltd.

Lead Sponsor

Trials

12

Recruited

3,400+

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

MCL1 is more frequently amplified and expressed in breast cancer subtypes compared to other antiapoptotic proteins like BCL2 and BCL2L1, indicating its significant role in cancer cell survival.

Targeting Mcl-1 with RNA interference effectively increased cell death in estrogen receptor-positive breast cancer cells, suggesting that Mcl-1-selective inhibitors could be a promising strategy to overcome resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade. Williams, MM., Lee, L., Hicks, DJ., et al.[2021]

ABT-199 is a selective BCL-2 inhibitor currently in clinical trials that shows promise in inducing cell death in hematopoietic tumors, but its effectiveness in solid tumors is less clear.

Combining ABT-199 with tamoxifen, a standard treatment for estrogen receptor-positive breast cancers, could enhance cancer cell death by targeting the BCL-2 protein, which is expressed in 85% of these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. Deng, J., Letai, A.[2021]

Combining H101, an oncolytic adenovirus targeting inactive p53, with siBCL2, a small interfering RNA targeting Bcl2, significantly enhances apoptosis and cytotoxicity in cancer cells compared to using either treatment alone.

In animal studies, this combined therapy not only inhibited tumor growth and prolonged survival but also resulted in complete tumor eradication in some cases, demonstrating a potent antitumor effect through simultaneous targeting of two common tumor-specific gene abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. Zhang, H., Wang, H., Zhang, J., et al.[2021]

ABT-199 is a selective small molecule inhibitor of BCL-2 that shows strong antitumor activity while sparing platelets, which is important for reducing side effects during cancer treatment.

Identifying assays that can predict the efficacy of ABT-199 in different tumors is essential for optimizing its use in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABT-199: taking dead aim at BCL-2. Davids, MS., Letai, A.[2021]

A specific subgroup of colorectal cancers with KRAS or BRAF mutations and BCL2L1 amplification can be effectively treated by combining the drugs ABT-263 and YM-155, which target BCL-XL and MCL1 respectively.

This combination therapy demonstrated a synergistic effect in both laboratory tests and in patient-derived xenograft models, suggesting it could be a promising treatment strategy for patients with these genetic alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Combination Treatment Targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified Colorectal Cancers. Cho, SY., Han, JY., Na, D., et al.[2022]

References

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

Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade. [2021]

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

Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. [2021]

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

Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. [2021]

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

ABT-199: taking dead aim at BCL-2. [2021]

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

A Novel Combination Treatment Targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified Colorectal Cancers. [2022]