LB-LR1109 for Cancer

(LB-LR1109 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: LG Chem

Disqualifiers: Cardiac disease, CNS metastases, Autoimmune, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1, first-in-human (FIH), multi-center, open-label, non-randomized, dose escalation study, designed to determine the Maximum tolerated dose(MTD)/Recommended Phase 2 dose(RP2D) of LB-LR1109 and to evaluate safety, tolerability, preliminary efficacy, pharmacokinetics, immunogenicity, pharmacodynamics of LB-LR1109, and its impact on quality of life in participants with unresectable and metastatic nonsmall cell lung cancer(NSCLC), head and neck squamous cell carcinoma(HNSCC), renal cell carcinoma(RCC), urothelial carcinoma, or malignant melanoma and no available standard of care treatment options.

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 study team or your doctor.

What makes the drug LB-LR1109 unique for cancer treatment?

LB-LR1109, also known as LR19155, is unique because it is an orally available drug that targets specific proteins (ALK and ROS1) involved in certain cancers, and it is designed to penetrate the blood-brain barrier, potentially offering benefits for patients with brain metastases. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with certain advanced cancers (like lung, kidney, throat cancer) that have worsened after standard treatments or who can't tolerate them. Participants need to provide a tumor sample and have an ECOG score of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

My cancer has spread and worsened after all standard treatments, or I can't tolerate them.

My organs are functioning well.

I am fully active or can carry out light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of LB-LR1109 to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

up to 1 year

Follow-up

Participants are monitored for safety, tolerability, and preliminary efficacy after treatment

4-8 weeks

Treatment Details

Interventions

• LB-LR1109

Trial Overview LB-LR1109 is being tested in this Phase 1 trial to find the highest dose patients can take without serious side effects (MTD), assess its safety and early signs of effectiveness, how it's processed by the body (pharmacokinetics), immune response it triggers (immunogenicity), and its impact on patients' quality of life.

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

LB-LR1109 is already approved in United States for the following indications:

Approved in United States as LB-LR1109 for:

• None approved; currently in Phase 1 clinical trial for unresectable and metastatic non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, or malignant melanoma

Who Is Running the Clinical Trial?

LG Chem

Lead Sponsor

Trials

66

Recruited

33,800+

Shin Hak-Cheol

LG Chem

Chief Executive Officer since 2022

Bachelor's degree in Mechanical Engineering from Seoul National University

Ko Yoon-joo

LG Chem

Chief Medical Officer

MD from Yonsei University

Findings from Research

CH5424802 is a potent and selective oral inhibitor of the ALK tyrosine kinase, showing strong antitumor activity against cancers with ALK gene alterations, such as nonsmall cell lung cancer and anaplastic large-cell lymphoma.

This inhibitor effectively targets the ALK L1196M mutation, which is known to confer resistance to other kinase inhibitors, suggesting its potential for treating patients with ALK-driven tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Sakamoto, H., Tsukaguchi, T., Hiroshima, S., et al.[2022]

PF06463922 is a selective inhibitor of ALK and ROS1, showing promising antitumor efficacy in non-small cell lung cancer models with specific mutations, indicating its potential as a targeted therapy.

The study established that achieving at least 60% inhibition of ALK is necessary for tumor stasis, suggesting this level of inhibition should be a target for future clinical trials in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational pharmacokinetic-pharmacodynamic modeling for an orally available novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1. Yamazaki, S., Lam, JL., Zou, HY., et al.[2021]

Lorlatinib, an ALK and ROS1 inhibitor for non-small-cell lung cancer, shows high brain accumulation, but this is significantly limited by the P-glycoprotein/ABCB1 transporter at the blood-brain barrier, which can be reversed by the coadministration of the inhibitor elacridar.

The oral availability of lorlatinib is notably restricted by the enzyme CYP3A4, indicating that understanding these transport mechanisms can help optimize its therapeutic use in patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib. Li, W., Sparidans, RW., Wang, Y., et al.[2021]

LDK378 (ceritinib) effectively reduces cell viability and induces cell death in rhabdomyosarcoma (RMS) cell lines at low micromolar concentrations, regardless of ALK expression levels, suggesting its potential as a treatment option for RMS.

The combination of LDK378 with the kinase inhibitor sorafenib shows a synergistic effect, enhancing cell death and reducing long-term colony formation in RMS cells, indicating a promising strategy for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhabdomyosarcoma cells are susceptible to cell death by LDK378 alone or in combination with sorafenib independently of anaplastic lymphoma kinase status. Dolgikh, N., Fulda, S.[2018]

XK469 is a novel antitumor agent that effectively induces cell cycle arrest in human U-937 leukemia cells at the G(2)/M phase, demonstrating its potential as a treatment for drug-resistant tumors.

The mechanism of action for XK469 involves the inhibition of the MEK/MAPK signaling pathways, leading to antiproliferative effects without significant cytotoxicity compared to conventional anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XK469, a novel antitumor agent, inhibits signaling by the MEK/MAPK signaling pathway. Lin, H., Subramanian, B., Nakeff, A., et al.[2021]

References

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

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. [2022]

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

Translational pharmacokinetic-pharmacodynamic modeling for an orally available novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1. [2021]

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

P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Rhabdomyosarcoma cells are susceptible to cell death by LDK378 alone or in combination with sorafenib independently of anaplastic lymphoma kinase status. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

XK469, a novel antitumor agent, inhibits signaling by the MEK/MAPK signaling pathway. [2021]