YL-17231 for Solid Tumors

Recruiting at 2 trial locations

Overseen By David S. Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.

Must not be taking: Chemotherapy, Immunotherapy, Biologics, Hormonal

Disqualifiers: Brain metastases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety, tolerability, drug levels, pharmacodynamic effects, and clinical activity of YL 17231 in patients with advanced solid tumors harboring mutations in KRAS, HRAS, or NRAS.

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 is a required 'washout period' (time without taking certain medications) for prior anti-tumor therapies, which varies depending on the type of therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug YL-17231 for solid tumors?

Research on a similar drug, YM529, shows it can kill cancer cells in various types of tumors, including lung and breast cancer, by causing the cells to self-destruct. This suggests that YL-17231 might also be effective against solid tumors. ^{1 2 3 4 5}

Is YL-17231 safe for humans?

The WT1 peptide vaccine, which may be related to YL-17231, has been tested in patients with various cancers and was generally well-tolerated with minimal side effects. Clinical trials showed that it could be administered safely, with some patients experiencing mild reactions like delayed hypersensitivity. ^{6 7 8 9 10}

Eligibility Criteria

Adults (≥18 years) with advanced solid tumors that have specific mutations in KRAS, HRAS, or NRAS genes and no standard treatment options left. They should be able to swallow pills, not have active infections or other cancers needing treatment, and must not be pregnant or breastfeeding. Participants need a life expectancy of at least 12 weeks, good performance status (able to carry out daily activities), adequate organ function, and acceptable blood counts.

Inclusion Criteria

You are able and willing to give written authorization and comply with the study protocol.

Women of childbearing potential must demonstrate commitment to using an effective form of contraception for at least 30 days prior to the commencement of treatment and 3 months following its conclusion.

I have not had any cancer treatments or major surgeries in the required waiting periods before starting this trial.

Exclusion Criteria

Patients who are pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the screening visit through 3 months after the last dose of trial treatment.

I have had serious heart issues or uncontrolled systemic diseases in the last 6 months.

I have chronic hepatitis B with low viral load or cured hepatitis C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase Ia)

3+3 design dose escalation study to evaluate safety, tolerability, and determine the MTD and/or RP2D of YL-17231

21 days per cycle, multiple cycles

Regular visits for dose escalation and monitoring

Dose Expansion (Phase Ib)

Dose expansion phase to further evaluate safety, tolerability, and preliminary anti-tumor activity at the RP2D

21 days per cycle, multiple cycles

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 months

Treatment Details

Interventions

• YL-17231

Trial Overview The trial is testing YL-17231's effects on patients with certain genetic mutations in their tumors. It looks at how safe the drug is, what side effects it causes, how the body processes it, and whether it helps control cancer growth.

Participant Groups

Group I: Dose Escalation and Expansion Experimental Treatment 1 Intervention

Dose escalation of YL-17231 to determine maximum tolerated dose.Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of YL-17231 to recommend Phase 2 regimens

Who Is Running the Clinical Trial?

Shanghai YingLi Pharmaceutical Co. Ltd.

Lead Sponsor

Trials

24

Recruited

2,400+

Findings from Research

The WT1 peptide vaccine has shown promising clinical responses in patients with hematological malignancies, particularly myelodysplastic syndromes and acute myeloid leukemia, indicating its potential as an effective immunotherapy.

Recent studies suggest that WT1 peptide vaccination may lead to cures in patients with minimal residual disease after chemotherapy or stem cell transplantation, highlighting its significant therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy. Oka, Y., Tsuboi, A., Nakata, J., et al.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

The third-generation bisphosphonates inhibit proliferation of murine osteosarcoma cells with induction of apoptosis. [2006]

2. Japan pubmed.ncbi.nlm.nih.gov

Apoptosis-inducing effect of a new bisphosphonate, YM529, on various hematopoietic tumor cell lines. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines. [2018]

4. Ireland pubmed.ncbi.nlm.nih.gov

Induction of mitochondria-dependent apoptosis through the inhibition of mevalonate pathway in human breast cancer cells by YM529, a new third generation bisphosphonate. [2015]

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

Establishment and characterization of a DOT1L inhibitor-sensitive human acute monocytic leukemia cell line YBT-5 with a novel KMT2A-MLLT3 fusion. [2020]

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

Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. [2022]

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

WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides. [2021]

8. England pubmed.ncbi.nlm.nih.gov

A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. [2022]

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

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy. [2018]