YL201 for Solid Tumors

Recruiting at 90 trial locations

Overseen By Alan Xu, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Must not be taking: Topoisomerase inhibitors, ADCs

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

312 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called YL201 for individuals with advanced solid tumors. The aim is to determine the optimal dose and assess the safety and effectiveness of this treatment for those whose tumors have not responded to or lack other treatment options. The trial consists of two parts: the first part identifies the appropriate dose, and the second part examines the safety and effectiveness of that dose in more detail. Individuals with solid tumors, such as small cell lung cancer or esophageal cancer, who have found available treatments ineffective or cannot tolerate them, might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment 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 requires that you stop taking certain medications before starting the study drug. Specifically, you must not have had chemotherapy, targeted therapy, hormonal therapy, or immunotherapy within 3 weeks before the first dose, and certain other treatments have specific time frames. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that YL201 is likely to be safe for humans?

Research shows that YL201 is generally safe for patients with advanced solid tumors. Studies have found that YL201 is usually well-tolerated, meaning most patients can handle it without major safety problems. Patients who previously received other treatments have used YL201 without serious issues. No clear evidence links YL201 to severe side effects. This trial remains in the early stages, focusing on identifying the safest dose for people. While some side effects might occur, early research suggests they can be managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for solid tumors rely on traditional chemotherapy or radiation, which target rapidly dividing cells but can affect healthy tissues. YL201 is unique because it utilizes a new mechanism of action, potentially targeting tumor cells more precisely and sparing healthy ones. Researchers are excited because this targeted approach could reduce side effects and improve outcomes for patients. Additionally, YL201 is being tested in different dose levels to optimize its effectiveness and safety, offering a tailored treatment option that current therapies may lack.

What evidence suggests that YL201 might be an effective treatment for solid tumors?

Research has shown that YL201 yields promising results for treating advanced solid tumors. In studies with 287 patients, YL201 reduced tumor size in about 41 out of every 100 patients. It targets B7-H3, a protein on many cancer cells, enabling effective cancer attack. Tests in animals, such as mice, also demonstrated strong anti-tumor effects across various cancer types. Overall, YL201 appears to be a hopeful treatment option for patients with hard-to-treat solid tumors. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that haven't responded to existing treatments or have no standard treatment options. Participants must be over 18, able to follow the study plan, and provide tumor tissue samples. They should not have active hepatitis B/C, unresolved toxicities from previous cancer therapies (except certain conditions), or any condition that could affect participation.

Inclusion Criteria

I am fully active or can carry out light work.

My advanced cancer has not responded to standard treatments, or there are none available.

Able and willing to comply with protocol visits and procedures

Exclusion Criteria

My brain or spinal cord cancer is stable without needing steroids or seizure medicine.

I need frequent procedures to remove excess body fluid.

I have been diagnosed with Gilbert's syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1: Estimate the MTD/RED(s) in dose escalation cohorts of patients with advanced solid tumors

Approximately 12 months

Dose Expansion

Part 2: Enroll patients with selected advanced solid tumor types at the MTD/RED(s) to define safety and evaluate efficacy

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 12 months

What Are the Treatments Tested in This Trial?

Interventions

• YL201

Trial Overview YL201 is being tested in a phase 1 trial involving two parts: dose escalation to find the maximum tolerated dose/recommended dosing, and dose expansion at these doses in selected tumor types. The goal is to determine safety and effectiveness of YL201 for patients with advanced solid tumors.

How Is the Trial Designed?

Group I: Dose expansion Experimental Treatment 1 Intervention

All participants enrolled in the dose expansion part

Group II: Dose escalation Experimental Treatment 1 Intervention

All participants enrolled in the dose escalation part

Group III: Dose Selection Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

MediLink Therapeutics (Suzhou) Co., Ltd.

Lead Sponsor

Trials

12

Recruited

3,400+

Published Research Related to This Trial

HLX07, a new anti-EGFR antibody, was found to be well tolerated in patients with advanced solid cancers, with no dose-limiting toxicities reported at doses up to 800 mg per week.

The most common treatment-emergent adverse events included fatigue and nausea, but only one serious adverse event was possibly related to the treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers. Hou, MM., Ho, CL., Lin, HY., et al.[2022]

ONC201, an anti-cancer compound in Phase II clinical trials, has shown strong anti-proliferative and pro-apoptotic effects on tumor cells while sparing normal cells, indicating its potential safety and efficacy in treating advanced cancers.

The drug works through a unique mechanism that activates the integrated stress response, leading to increased levels of the death ligand TRAIL, and has been confirmed to be well-tolerated in humans with a recommended dose of 625 mg every three weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and clinical introduction of first-in-class imipridone ONC201. Allen, JE., Kline, CL., Prabhu, VV., et al.[2021]

M7824, a novel bifunctional fusion protein targeting PD-L1 and TGFβ, demonstrated a manageable safety profile in a phase I trial with 19 heavily pretreated patients, with no maximum tolerated dose reached.

Early efficacy signals were observed, including one complete response in cervical cancer and two partial responses in pancreatic and anal cancers, suggesting potential for further investigation in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors. Strauss, J., Heery, CR., Schlom, J., et al.[2022]

In a phase I study involving 37 patients with advanced solid tumors and lymphomas, the novel anti-PD-L1 monoclonal antibody MSB2311 was found to have a manageable safety profile, with no dose-limiting toxicities reported and a maximum tolerated dose not reached.

MSB2311 showed promising antitumor activity, achieving a 30% objective response rate in biomarker-positive solid tumors, with a median duration of response of 11 months, indicating its potential effectiveness in treating these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of MSB2311, a novel pH-dependent anti-PD-L1 monoclonal antibody, treating patients with advanced solid tumors and lymphoma. Zhang, Q., Zhang, J., Zhong, H., et al.[2023]

The maximum-tolerated dose (MTD) of E6201 was determined to be 320 mg/m2 administered once weekly, based on a phase 1 study involving 55 patients with advanced solid tumors, including melanoma.

E6201 was found to be reasonably well-tolerated, with some adverse events like QT prolongation, and showed clinical efficacy with partial responses in patients, particularly those with BRAF-mutated melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study. Tibes, R., Borad, MJ., Dutcus, CE., et al.[2019]

In a phase II trial involving 22 patients with recurrent or refractory metastatic breast or endometrial cancer, ONC201 did not achieve any objective tumor responses, with an overall response rate of 0%.

Despite the lack of significant tumor response, ONC201 was found to have an acceptable safety profile, with all patients experiencing low-grade adverse events and only four patients experiencing grade 3 adverse events, indicating it may be safe for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma. Atkins, SLP., Greer, YE., Jenkins, S., et al.[2023]

ONC201 is a promising antitumor agent that induces apoptosis in triple-negative breast cancer (TNBC) cells, including those resistant to TRAIL, and is currently undergoing phase II clinical trials for various cancers.

The mechanism of action involves the activation of the transcription factor ATF4, which is crucial for ONC201's effectiveness; however, TNBC cells that develop resistance to ONC201 also show compromised ATF4 activation, indicating a potential challenge in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells. Yuan, X., Kho, D., Xu, J., et al.[2021]

ONC201 (TIC10) induces cancer cell death by activating the integrated stress response (ISR), which increases the pro-apoptotic protein TRAIL and involves key factors like ATF4 and CHOP, making it a promising treatment for various malignancies.

The mechanism of action includes rapid cell cycle arrest and decreased levels of cyclin D1 and mTORC1 activity, demonstrating that ONC201's effects are effective regardless of the p53 mutation status in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases. Kline, CL., Van den Heuvel, AP., Allen, JE., et al.[2022]

ONC201 is a promising cancer treatment that works by targeting the dopamine receptor D2 and activating mitochondrial protease ClpP, leading to tumor cell death through various mechanisms, including TRAIL-mediated apoptosis.

This drug is effective against certain cancers, particularly those with high levels of DRD2 and ClpP, and shows potential for synergy with other treatments like chemotherapy and immunotherapy, making it a versatile option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ONC201 and imipridones: Anti-cancer compounds with clinical efficacy. Prabhu, VV., Morrow, S., Rahman Kawakibi, A., et al.[2021]

In a network meta-analysis of six phase III clinical trials involving 4053 patients, PD-L1 inhibitor monotherapy was found to significantly reduce the risk of treatment-related adverse events (AEs) compared to platinum-based chemotherapy, with a risk ratio of 0.722 for any grade AEs and 0.406 for grade 3-5 AEs.

While PD-L1 inhibitors showed improved safety outcomes overall, they were associated with a higher risk of immune-related AEs compared to chemotherapy, indicating a need for careful monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. García Campelo, MR., Arriola, E., Campos Balea, B., et al.[2021]

Citations

1. cancernetwork.com cancernetwork.com/view/yl201-demonstrates-tolerability-early-efficacy-in-advanced-solid-tumors

YL201 Demonstrates Tolerability, Early Efficacy in ... Among 287 patients across multiple solid tumor indications, YL201 had an objective response rate of 40.8%, with a disease control rate of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05434234

A Study of YL201 in Patients With Advanced Solid Tumors This is a phase 1, multicenter, nonrandomized, open-label, first-in-human study of YL201 conducted in China and the United States.

3. nature.com nature.com/articles/s41591-025-03600-2

A B7H3-targeting antibody–drug conjugate in advanced ... In a preclinical study, YL201 exhibited potent anti-tumor activity in various CDX/PDX mouse models with SCLC, NSCLC, esophageal cancer and ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02191-4/fulltext

605O YL201, a novel B7H3-targeting antibody-drug ... YL201 has demonstrated encouraging efficacy in heavily pretreated advanced solid tumors with manageable safety and tolerability profile.

5. jto.org jto.org/article/S1556-0864(25)00521-0/fulltext

329P: Intracranial efficacy of YL201, a novel B7-H3 ... YL201 is a B7-H3-targeting ADC which has shown promising clinical activity in multiple advanced solid tumors. ... data mining, AI training, and similar ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07208773

A Study of YL201 and Ivonescimab (AK112) in Advanced ... This study was designed to evaluate the efficacy and safety of YL201 in combination with Ivonescimab (AK112) in subjects with solid tumor.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05434234

A Study of YL201 in Patients With Advanced Solid Tumors This is a phase 1, multicenter, nonrandomized, open-label, first-in-human study of YL201 conducted in China and the United States. The study will include 2 ...