ABSK112 for Lung Cancer

Recruiting at 13 trial locations

Overseen By Yinan Lin

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Abbisko Therapeutics Co, Ltd

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing ABSK112, a new drug, in patients with advanced lung cancer that has a specific genetic mutation. The goal is to see if the drug is safe and if it can help stop the cancer from growing.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications that affect the CYP3A enzyme family within 2 weeks before starting the trial, and you should avoid certain fruits and juices like grapefruit and pomegranate 3 days before starting. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug ABSK112 for lung cancer?

Research shows that targeting the ALK gene, which is involved in some lung cancers, with ALK inhibitors can shrink tumors and improve survival. ABSK112 may work similarly by targeting ALK mutations, as seen with other ALK inhibitors like crizotinib and alectinib, which have shown effectiveness in treating ALK-positive lung cancer. ^{1 2 3 4 5}

What safety data is available for ABSK112 (or similar ALK inhibitors) in humans?

ALK inhibitors, which may include treatments like ABSK112, have been associated with various side effects, including lung toxicity and other serious adverse events. While most side effects are mild, serious ones can occur in over 20% of patients, so careful monitoring is important. ^{6 7 8 9 10}

Eligibility Criteria

Adults with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who have tried other treatments without success, or for whom no standard treatment is available. Participants must be over 18, understand the study and consent to it, have a life expectancy of at least 3 months, and good organ function. Women of childbearing age and men must agree to use effective birth control.

Inclusion Criteria

Patients must have at least one measurable target lesion according to RECIST v1.1

My condition worsened after standard treatment, or I can't tolerate it, or there's no standard treatment for me.

My organs and bone marrow are working well.

Exclusion Criteria

I cannot take pills by mouth or have serious digestive issues.

I have fluid buildup that's hard to control or needed treatment recently.

I haven't had a live vaccine in the last 4 weeks, but inactive vaccines like COVID-19 are okay.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ABSK112 in repeated 28-day cycles to determine the maximum tolerated dose

28 days per cycle

Dose Expansion

Participants receive ABSK112 at the recommended dose of expansion to evaluate safety, tolerability, and preliminary antitumor activity

Assessed up to 50 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after the last dose

Treatment Details

Interventions

• ABSK112 (Monoclonal Antibodies)

Trial Overview ABSK112 is being tested in this phase 1 trial for safety, tolerability, how the body processes it (pharmacokinetics), and initial effectiveness against NSCLC. The study is open-label meaning everyone knows what treatment they're getting; non-randomized so there's no chance element in assigning treatments.

Participant Groups

Group I: ABSK112 Experimental Treatment 1 Intervention

During the escalation part, the administration of oral ABSK112 will be guided by Bayesian optimal interval (BOIN) design based on safety data collected until a maximum tolerated dose (MTD) has been identified. The first dose level will be administered as QD, and different dosing frequencies (e.g., BID) may be explored in subsequent doses depending on emerging safety and pharmacokinetic data. A separate food effect cohort may be conducted. In expansion part, patients will be treated at the selected RDE dose level.

Who Is Running the Clinical Trial?

Abbisko Therapeutics Co, Ltd

Lead Sponsor

Trials

26

Recruited

1,700+

Findings from Research

This study identified six novel mutations in the ALK gene that contribute to lung adenocarcinomas, leading to increased cell proliferation and tumor growth through hyperphosphorylation of ALK and activation of oncogenic signaling pathways.

Treatment with ALK inhibitors significantly reduced tumor size and metastasis in mouse models, suggesting that targeting these mutations could enhance treatment outcomes for patients with lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. Wang, YW., Tu, PH., Lin, KT., et al.[2021]

Alectinib is currently the standard first-line treatment for patients with ALK+ non-small cell lung cancer (NSCLC), demonstrating superior efficacy and safety compared to previous therapies.

New ALK-tyrosine-kinase inhibitors (TKIs) like lorlatinib and ensartinib are in development to address resistance mutations, showing promise but requiring further research to confirm their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment of advanced non-small cell lung cancer with ALK rearrangement: state of the art and future development. Rocco, D., Della Gravara, L., Battiloro, C., et al.[2022]

In an 81-year-old male with ALK-rearranged non-small-cell lung cancer, crizotinib treatment initially caused severe adverse events, including acute renal failure and congestive heart failure, necessitating a modified treatment approach.

The case report highlights that administering crizotinib on a 'skip schedule' (250 mg twice daily every 3 days) was more effective in controlling tumor progression than simply reducing the daily dose, maintaining anti-tumor effects for 13 months despite the patient's severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Crizotinib schedule for an elderly patient with ALK rearranged non-small-cell lung cancer: a case report. Fukuizumi, A., Miyanaga, A., Seike, M., et al.[2018]

The ALK tyrosine kinase inhibitor TAE684 effectively inhibits cell proliferation and induces apoptosis in certain EML4-ALK-positive NSCLC cell lines by targeting the STAT3 and ERK signaling pathways.

Combining TAE684 with a MEK inhibitor significantly enhances apoptosis in resistant EML4-ALK-positive NSCLC cells by simultaneously disrupting both the STAT3-survivin and ERK-BIM pathways, suggesting a potential strategy for improving treatment outcomes in patients who do not respond to ALK inhibitors alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells. Tanizaki, J., Okamoto, I., Takezawa, K., et al.[2021]

Alectinib shows significant clinical activity in patients with advanced ALK+ non-small-cell lung cancer, achieving a median overall survival of 29.1 months in a pooled analysis of 225 patients from two phase II studies.

The safety profile of alectinib is manageable, with common side effects including constipation, fatigue, and peripheral edema, and no new safety concerns were identified during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Ou, SI., Gadgeel, SM., Barlesi, F., et al.[2021]

A pharmacovigilance analysis of ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) revealed significant safety signals, including serious adverse events like pulmonary arterial hypertension and rectal perforation, indicating the need for further regulatory investigation.

Specific safety concerns were identified for each drug, such as eye disorders with crizotinib and myasthenia gravis with lorlatinib, highlighting the importance of monitoring these effects to inform patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS). Omar, NE., Fahmy Soliman, AI., Eshra, M., et al.[2022]

A study of 130 treatment courses in 111 patients revealed that safety monitoring activities (SMAs) for EGFR and ALK inhibitors were inconsistently conducted, with prevalence ranging from 10.0% to 84.6%, and 31.5% of courses had no SMAs performed.

EGFR inhibitors were associated with a higher likelihood of SMAs being conducted compared to ALK inhibitors, highlighting the need for clinicians to closely follow FDA guidelines to ensure patient safety and monitor for serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. Singh, AM., Rubiera-Pebe, R., Ahmad, Y., et al.[2023]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

A meta-analysis of 19 studies found that serious adverse events (SAEs) related to ALK inhibitors occurred in over 20% of patients, with ceritinib and brigatinib showing SAEs in more than 40% of participants, highlighting significant safety concerns.

Among the ALK inhibitors analyzed, alectinib was identified as the safest option, suggesting it may be preferable for patients due to its lower incidence of SAEs, particularly lung toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. Hou, H., Sun, D., Liu, K., et al.[2020]

Alectinib, an ALK inhibitor for lung cancer, is associated with a significant risk of lung toxicity, particularly interstitial lung disease, which has a reporting odds ratio of 10.28, indicating a strong causal relationship.

Interstitial lung disease typically develops within 60 days of starting alectinib treatment, highlighting the importance of monitoring patients for lung-related adverse effects early in their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Lung Toxicity Related to the Treatment With Alectinib Using a Pharmacovigilance Database. Sato, J., Uchida, M., Wakabayashi, H., et al.[2022]

References

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

Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

First-line treatment of advanced non-small cell lung cancer with ALK rearrangement: state of the art and future development. [2022]

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

Effective Crizotinib schedule for an elderly patient with ALK rearranged non-small-cell lung cancer: a case report. [2018]

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

Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS). [2022]

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

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Lung Toxicity Related to the Treatment With Alectinib Using a Pharmacovigilance Database. [2022]