YL217 for Cancer

Recruiting at 3 trial locations

Overseen By Qiaoyun Wang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Topoisomerase inhibitors, Steroids

Disqualifiers: Cardiovascular, Pulmonary, HIV, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

220 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, there is a requirement for an adequate washout period (time without taking certain medications) for prior anticancer treatments before starting the study drug.

What safety data exists for YL217 or similar treatments?

The safety data for similar treatments like apatinib (YN968D1) and immunotherapy combined with antiangiogenic therapy show that most side effects are mild and include issues like skin problems, fatigue, and digestive issues. No drug-related deaths were reported, and these treatments were generally well tolerated. ^{1 2 3 4 5}

How does the drug YL217 differ from other cancer treatments?

YL217 targets CD147, a protein overexpressed in many aggressive cancers, which plays a key role in cancer cell survival and spread. By inhibiting CD147, YL217 may prevent cancer growth and improve the effectiveness of existing treatments, offering a novel approach compared to traditional therapies. ^{6 7 8 9 10}

Eligibility Criteria

Adults aged 18+ with advanced solid tumors, including certain gastrointestinal cancers, who can sign consent and follow study procedures. They must have at least one measurable tumor lesion, good organ function, and an ECOG performance status of 0 or 1. Those with HIV, recent major surgery, severe lung issues or specific prior treatments are excluded.

Inclusion Criteria

I have signed the informed consent form for this study.

Able and willing to comply with protocol visits and procedures

My organs and bone marrow are working well.

Exclusion Criteria

Concurrent enrollment in another clinical study, unless it is an observational clinical study

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

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of YL217 to determine the maximum tolerated dose

Up to 3 years

Backfill

Participants are enrolled at safe and tolerable dose levels determined in the dose escalation phase

Up to 3 years

Dose Expansion

Dose optimization is performed in disease-specific cohorts with random assignment to dose regimens

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• YL217

Trial Overview The trial is testing YL217, a new drug given as an intravenous infusion every three weeks to patients with various advanced solid tumors. It's the first time this drug is being tested in humans to see how safe it is and how well it works.

Participant Groups

Group I: The dose escalation stage, backfill stage and dose expansion stage of YL217 Experimental Treatment 1 Intervention

Part 1: The dose escalation stage：A preliminary anticipated dose-escalation sequence is 0.5, 1.0, 2.0, 3.0, and 4.0 mg/kg. Part 2: Backfill stage：Patients will be enrolled at one or more dose levels that do not exceed the dose that is deemed safe and tolerable in dose escalation. Then at least two dose levels will be selected as the recommended dose for expansion (RDE). Part 3: The dose expansion stage：Dose optimization will be performed in at least one of disease-specific cohorts where patients will be randomly assigned to two dose regimens in a 1:1 ratio.

Who Is Running the Clinical Trial?

MediLink Therapeutics (Suzhou) Co., Ltd.

Lead Sponsor

Trials

12

Recruited

3,400+

Findings from Research

In a phase II trial involving 30 patients with advanced non-squamous non-small cell lung cancer (NSCLC), the combination of apatinib and docetaxel resulted in a disease control rate of 96.6% and a partial remission rate of 27.6%.

The treatment was found to be tolerable, with most adverse events being mild to moderate (grade 1-2), including hypertension and hand-foot syndrome, indicating that apatinib plus docetaxel is a safe option for patients with wild-type EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of apatinib and docetaxel in treating advanced non-squamous non-small cell lung cancer patients with wild-type EGFR: a multi-center, phase II trial. Song, Y., Miao, L., Wang, Z., et al.[2022]

In a study of 78 BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma treated with dabrafenib and trametinib, the median overall survival was over 2 years, with 72% of patients alive at 1 year and 47% at 3 years.

Approximately 20% of patients were progression-free at 3 years, with better outcomes associated with having fewer than three organ metastases and lower baseline lactate dehydrogenase levels, suggesting these factors may help predict durable responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. Long, GV., Weber, JS., Infante, JR., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

CD147 is a key protein overexpressed in various aggressive cancers, playing a crucial role in cancer growth, survival, and metastasis through multiple signaling pathways.

Targeting CD147 with therapies, such as monoclonal antibodies, has shown promise in enhancing treatment efficacy and reducing side effects in chemoradiotherapy and other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD147: an integral and potential molecule to abrogate hallmarks of cancer. Nyalali, AMK., Leonard, AU., Xu, Y., et al.[2023]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Clinical investigation of the efficacy and toxicity of apatinib (YN968D1) in stage III/IV non-small cell lung cancer after second-line chemotherapy treatment: A retrospective study. [2019]

2. China pubmed.ncbi.nlm.nih.gov

Combination of apatinib and docetaxel in treating advanced non-squamous non-small cell lung cancer patients with wild-type EGFR: a multi-center, phase II trial. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies. [2021]

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

Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. [2022]

5. England pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

CD147: an integral and potential molecule to abrogate hallmarks of cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Co‑expression of Lewis y antigen and CD147 in epithelial ovarian cancer is correlated with malignant progression and poor prognosis. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy Evaluation of Combination Treatment Using Gemcitabine and Radioimmunotherapy with 90Y-Labeled Fully Human Anti-CD147 Monoclonal Antibody 059-053 in a BxPC-3 Xenograft Mouse Model of Refractory Pancreatic Cancer. [2022]