YH42946 for Cancer

Recruiting at 14 trial locations

Overseen By Yuhan Corporation Clinical Operation Team 1

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yuhan Corporation

Disqualifiers: Brain metastases, Heart failure, ILD, others

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

Compensation: Varies

Number of Visits: Unknown

161 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called YH42946 for individuals with certain advanced cancers that have specific genetic changes. Researchers aim to determine the safety and effectiveness of YH42946 against tumors with HER2 or EGFR mutations, which can drive cancer growth. The trial targets individuals with advanced or metastatic tumors, particularly those who have exhausted all standard treatments without success. Participants must have a confirmed HER2 or EGFR mutation in their tumors and stable brain lesions if present. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that YH42946 is likely to be safe for humans?

Research has shown that YH42946 is a treatment designed for certain difficult-to-treat tumors. It targets specific changes in cancer cells, such as HER2 and EGFR exon 20 insertions, which often resist standard treatments. Early tests demonstrated that YH42946 acts on these changes without harming normal cells, indicating a positive safety profile.

Detailed safety information from human studies is not yet available, as the treatment is still in the early stages of clinical trials. These stages primarily focus on assessing how well people tolerate the treatment and determining the appropriate dose.

If YH42946 had been approved for another condition, it might provide some insights into its safety. However, without specific human safety data, it is crucial to understand that this is a new treatment still under careful study. Participants in such trials are vital for discovering new, effective treatments, but discussing potential risks with a healthcare provider is also important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about YH42946 for cancer treatment because it introduces a new mechanism of action that differs from standard therapies like chemotherapy and targeted drugs. Most traditional cancer treatments work by destroying rapidly dividing cells or inhibiting specific proteins involved in cancer growth. However, YH42946 uniquely targets and modulates specific pathways involved in cancer cell survival, potentially leading to better outcomes with fewer side effects. This innovative approach could offer new hope for patients who have not responded well to existing treatments.

What evidence suggests that YH42946 might be an effective treatment for cancer?

Research has shown that YH42946 is a promising treatment for certain genetic changes in cancer cells. It targets tumors with specific alterations in the HER2 and EGFR genes, which often resist standard treatments. Early lab studies demonstrated that YH42946 effectively blocked these cancer-causing changes while sparing normal cells. This targeted approach might offer a new option for patients with these hard-to-treat cancers. Although research in humans continues, these early results suggest it could help combat tumors. Participants in this trial will join a dose escalation arm to determine the maximum tolerated dose and a dose expansion part to select the recommended dose, with several independent cohorts planned. ^{1 2 4 6 7}

Who Is on the Research Team?

Judith Ertle, MD

Principal Investigator

Yuhan Corporation

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors, specifically those with HER2 or EGFR mutations who have exhausted standard treatments or can't receive them. Participants must have treated brain metastases if present, good kidney and liver function, stable blood counts without recent transfusions or growth factors, and a life expectancy of over 3 months.

Inclusion Criteria

I am fully active or can carry out light work.

My doctor expects me to live at least 3 more months.

My cancer has worsened despite all standard treatments or standard treatments are not suitable for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of YH42946 to determine the maximum tolerated dose

21 days

Multiple visits for dose escalation and monitoring

Dose Expansion

Participants receive selected doses of YH42946 to evaluate efficacy and safety

Approximately 12 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3.5 years

What Are the Treatments Tested in This Trial?

Interventions

• YH42946

Trial Overview The study tests YH42946's safety and effectiveness against advanced solid tumors with specific genetic changes. It's an early-phase trial assessing how the body processes the drug (pharmacokinetics) and its impact on tumor size (anti-tumor activity).

How Is the Trial Designed?

Group I: Part 1 and Part 2 Experimental Treatment 1 Intervention

Part 1: Dose escalation arm to determine the MTD Part 2: Dose expansion part to select RD. Several independent cohorts are planned.

Who Is Running the Clinical Trial?

Yuhan Corporation

Lead Sponsor

Trials

111

Recruited

27,800+

Cho Wook-je

Yuhan Corporation

Chief Executive Officer since 2021

Bachelor's degree in Agricultural Chemistry from Korea University

Kim Yeol-hong

Yuhan Corporation

Chief Medical Officer since 2024

Not available

Published Research Related to This Trial

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A follow-up program involving pharmacists for outpatients treated with oral antineoplastic agents (OAA) showed a reduction in severe adverse events (AEs) and major drug interactions compared to patients who were not monitored, indicating improved safety in the intervention group.

The study included 249 patients over a 6-month period, revealing that while AEs were still common, the intervention group experienced fewer severe AEs and had better monitoring of drug interactions, particularly with medications like erlotinib and gefitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents. Escudero-Vilaplana, V., Ribed, A., Romero-Jimenez, RM., et al.[2018]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

In a retrospective study of 123 patients receiving FOLFOX 4 chemotherapy for advanced colorectal cancer, significant adverse reactions were reported, including hemotoxicity (52.8%), chronic sensory neuropathy (16.2%), and allergic reactions (15.4%).

Common side effects during initial treatment included appetite loss (60.1%), vomiting (19.5%), and acute sensory neuropathy (33.3%), highlighting the need for improved patient education and pharmaceutical care to manage these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. Imada, H., Kawakami, K., Hiraoka, T., et al.[2013]

A large-scale retrospective study of 2094 cases from the FDA adverse event reporting system found that combining immune checkpoint inhibitors with bevacizumab significantly increases the risk of adverse drug reactions (ADRs) in cancer patients, particularly interstitial lung disease, hypertension, and gastrointestinal bleeding.

The study highlights that combination therapy is an independent risk factor for these ADRs, suggesting the need for careful monitoring and individualized management strategies for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. Gu, T., Jiang, A., Zhou, C., et al.[2023]

Citations

1. yuhan-usa.com yuhan-usa.com/yuhan-presents-preclinical-data-on-targeted-therapy-yh42946-and-bispecific-immunotherapy-yh32364/

Yuhan Presents Preclinical Data on Targeted Therapy ... YH42946, licensed from J INTS BIO in 2023, targets tumors with HER2 and EGFR exon 20 insertions, mutations often resistant to conventional TKIs, ...

2. delta.larvol.com delta.larvol.com/Products/?ProductId=1dfe02af-914a-4845-b7ca-710799a9eb15

YH42946 / J Ints Bio, Yuhan Corp YH42946 is a potent small-molecule inhibitor that selectively targets EGFR ex20ins while sparing EGFR WT in preclinical models, offering potential therapeutic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025002302

Review Current paradigm of EGFR ins20 in non-small cell ... Data from phase 2 are pending. YH42946. YH42946 is an innovative orally administered TKI designed to target HER2.

4. mk.co.kr mk.co.kr/en/society/11040919

Yuhan Corporation has begun developing a new drug for ... YH42946 was previously approved by the US Food and Drug Administration (FDA) last month for a phase 1 and 2 clinical trial plan. YH42946 is ...

5. linkedin.com linkedin.com/posts/yuhan-usa_aacr-%EC%9C%A0%ED%95%9C%EC%96%91%ED%96%89-%ED%95%AD%EC%95%94%EC%8B%A0%EC%95%BD-%ED%9B%84%EB%B3%B4-yh42946yh32364-activity-7325348603059728384-8zVH

Yuhan presents preclinical data on YH42946 and YH32364 Yuhan Corporation unveiled promising preclinical results for two of its cancer drug candidates: YH42946 ... New publication Phase II AUGMENT-101 ...

6. trial.medpath.com trial.medpath.com/clinical-trial/e5321d027f742461/nct06616766-yh42946-her2-egfr-tumor-study

A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate ... YH42946 showed potency for diverse HER2 aberrations including HER2 overexpression, amplification, or mutation, as well as EGFR Ex20ins. This is a Phase 1/2, ...

7. synapse.patsnap.com synapse.patsnap.com/drug/89cc723c881b40d4b2a73d80d39b6bdd

YH-42946 - Drug Targets, Indications, Patents A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, PK and Anti-tumor Activity of YH42946 in Patients With Locally Advanced ...