YH42946 for Cancer

Recruiting at 7 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

Trial Summary

What is the purpose of this trial?

The goal of this YH42946-101 is to evaluate the safety, Tolerability, Pharmacokinetics and anti-tumor activity of YH42946 in patients with locally advanced of metastatic solid tumors with HER2 aberration and EGFR exon 20 insertions.

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.

What safety data exists for the treatment YH42946 for cancer?

The safety of molecular target anticancer drugs, which may include treatments like YH42946, shows an increased risk of serious adverse events (SAEs) and fatal adverse events (FAEs) compared to placebo. Efforts are needed to prevent these occurrences in patients taking such drugs. ^{1 2 3 4 5}

Research Team

Jeongmin Kim

Principal Investigator

Yuhan Corporation

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

References

1. India 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. [2020]

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

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. [2013]

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

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents. [2018]

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

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. [2023]

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

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]