YL-15293 for Solid Tumors

Recruiting at 2 trial locations

Overseen By Meiyue G Hong, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: CNS involvement, Active infection, Cardiac issues, others

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

Compensation: Varies

Number of Visits: 2

Duration: Until disease progression or other criteria

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called YL-15293 for individuals with advanced solid tumors that have a specific KRAS G12C mutation. The goal is to determine the optimal dose and assess its safety and effectiveness, particularly for those with advanced non-small cell lung cancer (NSCLC) who lack other treatment options. It suits patients whose cancer has progressed despite previous treatments and who possess this specific genetic mutation. Participants will receive the treatment until their cancer progresses or they experience unacceptable side effects. 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 does not specify if you need to stop taking your current medications, but you cannot be on any concurrent chemotherapy, immunotherapy, or hormonal therapy for cancer treatment.

Is there any evidence suggesting that YL-15293 is likely to be safe for humans?

In previous studies, YL-15293 has demonstrated a safety profile manageable for patients with advanced solid tumors. Research indicates that side effects are usually mild to moderate, allowing most people to handle the treatment without major issues.

Specific safety data for this trial is not yet available, but YL-15293's progression to Phase 1/2 suggests earlier tests deemed it safe enough for further study. Phase 1/2 trials assess a treatment's safety, the body's tolerance, and help determine the best dose for future tests.

In summary, YL-15293 has been tested in other studies and has generally been well-tolerated by patients. For those considering joining a trial, it's reassuring that earlier tests have not revealed major safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often include chemotherapy, radiation, or immunotherapy, YL-15293 offers a unique approach by being an orally administered drug. This makes it potentially easier and more convenient for patients to take. Researchers are particularly excited about YL-15293 because it might offer a novel mechanism of action, potentially targeting cancer cells in a way that existing treatments do not. The potential for a new way to combat solid tumors is what makes this treatment stand out from current options.

What evidence suggests that YL-15293 might be an effective treatment for advanced solid tumors?

Research shows that YL-15293 targets tumors with a specific change in the KRAS gene, known as the G12C mutation. This mutation often appears in certain cancers, such as non-small cell lung cancer (NSCLC). Early studies on drugs like YL-15293, which block this mutation, have shown promise in halting tumor growth. Although detailed information about YL-15293 in humans remains limited, similar drugs have proven effective, with some patients responding well. This suggests that YL-15293 might help shrink tumors or slow their growth in individuals with the KRAS G12C mutation. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Part 1 only - metastatic or locally advanced solid tumor malignancies positive for KRAS G12C that has progressed on, is refractory to, intolerant to, or for which there is no curative standard of care therapy.

Part 2 only - metastatic or locally advanced KRAS G12C NSCLC for patients for whom there is no curative standard of care therapy.

Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria

Subjects who have received prior treatment with KRAS G12C targeted agents.

Patient has an active infection requiring systemic therapy.

Patients who have known active HIV, Hepatitis or Hepatitis or active COVID-19 infection. (Patients who have been vaccinated against Hepatitis B and who are positive only for the Hepatitis B surface antibody are permitted to participate in the study). Subjects who are positive for HIV or hepatitis B or C virus must be tested for and have an undetectable viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of YL-15293

4 weeks

Cycle 1, Day 1 and Day 28 visits for PK sampling

Treatment

Participants receive oral YL-15293 once daily until disease progression or other discontinuation criteria are met

Until disease progression or other criteria

Follow-up

Participants are monitored for safety for 30 days post-treatment and for disease assessment until new anticancer treatment or other criteria

30 days for safety follow-up

What Are the Treatments Tested in This Trial?

Interventions

• YL-15293

How Is the Trial Designed?

Group I: YL-15293 Experimental Treatment 1 Intervention

After a screening period of approximately 28 days, eligible patients will receive oral YL-15293 once daily until documented disease progression, unacceptable AEs, intercurrent illness prevents further administrations of study treatment, investigator's decision to withdraw the patient, the patient withdraws consent, pregnancy of the patient, or for administrative reasons. Following the end of treatment, patients will continue to be followed for safety for 30 days. Patients who permanently discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the Sponsor stops the study, whichever comes first.

Who Is Running the Clinical Trial?

Shanghai YingLi Pharmaceutical Co. Ltd.

Lead Sponsor

Trials

24

Recruited

2,400+

Yingli Pharma US, Inc

Collaborator

Trials

2

Recruited

110+

Published Research Related to This Trial

In a phase 1 clinical trial involving 108 patients with advanced NSCLC, YK-029A demonstrated a manageable safety profile with no dose-limiting toxicities and common side effects including anemia (50.9%) and diarrhea (49.1%).

Among 28 treatment-naive patients with EGFR exon 20 insertion mutations, YK-029A showed promising efficacy with an objective response rate of 73.1% and a disease control rate of 92.3%, indicating strong antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial. Duan, J., Wu, L., Yang, K., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05173805

NCT05173805 | Phase I Clinical Study of YL-15293 in ... This is a phase 1 / 2 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of oral YL-15293 in patients with advanced ...

2. synapse.patsnap.com synapse.patsnap.com/drug/e7f56181b737429bb9cad5ca166ecccb

YL-15293 - Drug Targets, Indications, Patents The linperlisib-treated patients (Full Analysis Set N = 88) evaluated by Lugano criteria, had a 48% overall response rate, including 30% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11228624/

Assessment of KRASG12C inhibitors for colorectal cancer This review provides an update on clinical trials involving CRC patients treated with KRAS G12C inhibitors as a monotherapy or combined with other drugs.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405803324002759

KRAS inhibitors: resistance drivers and combinatorial ... In this review, we highlight the progress on defining resistance mechanisms and developing combination treatment strategies to improve patient responses to ...

5. link.springer.com link.springer.com/article/10.1007/s44178-023-00032-1

Advances in KRAS mutation inhibition in metastatic ... All these preclinical findings strongly suggest that AMG 510 might be an effective anti-tumor agent targeting KRASG12C tumors as monotherapy or ...

6. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1252516/pdf

Prognostic and therapeutic impact of the KRAS G12C ... Safety data was comparable to the results seen in. NSCLC, with ... solid tumors. J Med Chem (2022) 65(24):16173–203. doi: 10.1021/acs ...

7. cap.org cap.org/member-resources/articles/an-emerging-role-of-pathologists-in-kras-mutation-testing-and-targeted-treatment

An Emerging Role of Pathologists in KRAS Mutation ... This article will discuss the frequency of KRAS mutations in various cancer types, introduce commonly used testing methods, and explore available KRAS ...