YL202 for Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new drug, YL202 (also known as BNT326), for patients with advanced lung and breast cancer. It specifically targets lung cancer with a certain genetic mutation (EGFR) and HR-positive, HER2-negative breast cancer that have resisted standard treatments. Patients may qualify if their cancer has worsened despite previous therapies, such as specific chemotherapy and other targeted drugs. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering patients the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that YL202 is likely to be safe for humans?

Research has shown that YL202 encountered some safety issues in early testing. One study identified five serious side effects linked to higher doses of YL202. Due to these risks, the FDA temporarily halted the trial to assess safety. However, the trial resumed after implementing changes to manage these risks. Although this might sound concerning, the trial's continuation indicates that the treatment is under careful safety monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cancer involve chemotherapy, surgery, or radiation, which can affect both healthy and cancerous cells. However, YL202 is unique because it targets cancer cells specifically through a novel mechanism of action. Researchers are excited about YL202 because it offers the potential for a more precise attack on cancer cells, minimizing harm to healthy cells and potentially resulting in fewer side effects. This targeted approach could make YL202 a game-changer in cancer treatment by improving patient outcomes and quality of life.

What evidence suggests that YL202 might be an effective treatment for EGFR-mutated NSCLC or HR-positive, HER2-negative BC?

Previous studies have shown that YL202 holds promise in treating certain types of cancer. YL202 is an antibody-drug conjugate (ADC) that targets the HER3 protein on cancer cells, designed to find and attack cells with this protein on their surface. For patients with non-small cell lung cancer (NSCLC) and breast cancer who have undergone multiple treatments, early results indicate that about 42% experienced a reduction or disappearance of their tumors after receiving YL202. Although these results are preliminary, they suggest YL202 could be effective for these difficult-to-treat conditions. Participants in this trial will receive YL202 in a dose escalation format to determine the optimal dosing. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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

My organs and bone marrow are working well.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. asco.org asco.org/abstracts-presentations/ABSTRACT458692

YL202/BNT326, a HER3-targeted ADC, in patients with ... We report preliminary safety and efficacy results from a phase I trial of YL202/BNT326. Methods: This multinational trial is recruiting patients (pts) with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3034

YL202/BNT326, a HER3-targeted ADC, in patients with ... We report preliminary safety and efficacy results from a phase I trial of YL202/BNT326. Methods: This multinational trial is recruiting ...

3. oncologypipeline.com oncologypipeline.com/apexonco/dosing-limit-solves-biontechs-clinical-hold

Dosing limit solves BioNTech's clinical hold | ApexOnco MediLink's phase 1 data with BNT326/YL202 ; Efficacy-evaluable patients (NSCLC & breast cancer), 24, 53, 29 ; ORR, 42%, 42%, 41%.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05653752

NCT05653752 | A Study of YL202 in Patients With Locally ... This is a phase 1, multicenter, open-label, first-in-human study of YL202 conducted in the United States and China. The study will evaluate the safety and ...

5. onclive.com onclive.com/view/fda-places-partial-clinical-hold-on-phase-1-trial-of-yl202-in-advanced-nsclc-and-breast-cancer

FDA Places Partial Clinical Hold on Phase 1 Trial of YL202 ... The FDA placed a partial clinical hold on a phase 1 trial evaluating YL202 in select patients with advanced non–small cell lung cancer or breast ...

6. investors.biontech.de investors.biontech.de/news-releases/news-release-details/lift-partial-clinical-hold-bnt326yl202

Lift of Partial Clinical Hold for BNT326/YL202 - BioNTech Based on emerging safety data from the ongoing trial evaluating BNT326/YL202, the companies swiftly and proactively took precautionary ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06439771

NCT06439771 | A Phase 2 Study to Evaluate the Efficacy, ... This study is a multicenter, open-label, phase 2 clinical study to evaluate the efficacy, safety and pharmacokinetics of YL202 in patients with locally ...

8. cancernetwork.com cancernetwork.com/view/fda-places-partial-hold-on-bnt326-yl202-trial-for-nsclc-breast-cancer

FDA Places Partial Hold on BNT326/YL202 Trial ... A trial for BNT326/YL202 in EGFR-mutated NSCLC or HR-positive HER2-negative breast cancer has paused enrollment due to a large illness or injury risk.