ABSK112 for Lung Cancer

Recruiting at 13 trial locations

Overseen By Yinan Lin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abbisko Therapeutics Co, Ltd

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ABSK112, to determine its safety and effectiveness in treating advanced or metastatic non-small cell lung cancer (NSCLC). Researchers aim to find the right dose and understand how the body processes the drug. The trial seeks participants whose cancer has specific mutations and who have not responded to other treatments. Participants should have at least one measurable tumor and be able to manage their blood pressure. 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 drug.

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.

Is there any evidence suggesting that ABSK112 is likely to be safe for humans?

Research shows that ABSK112 is undergoing safety testing in people with non-small cell lung cancer (NSCLC). This trial marks the first use of ABSK112 in humans, so limited safety information exists. In these early studies, researchers aim to assess patient tolerance and identify any side effects. The primary goal is to determine a safe dose and closely monitor for negative reactions. Although no previous human data is available, the trial will provide crucial safety information about ABSK112. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lung cancer, which often include chemotherapy, targeted therapy, and immunotherapy, ABSK112 is unique because it involves an innovative dosing strategy guided by Bayesian optimal interval design. This approach allows for the gradual adjustment of dosage based on real-time safety data, potentially optimizing the treatment's effectiveness and minimizing side effects. Researchers are particularly excited about ABSK112's flexibility in administration, as it can be taken orally with varying dosing frequencies, which may enhance patient convenience and outcomes.

What evidence suggests that ABSK112 might be an effective treatment for lung cancer?

Research has shown that ABSK112, the investigational treatment in this trial, targets a gene called ALK, which contributes to some lung cancers. Studies have found that ALK inhibitors can shrink tumors and improve survival rates. In lab tests on mice, ABSK112 showed strong anti-tumor effects, especially in cases with certain mutations. It also acts as a powerful HER2 inhibitor, suggesting potential effectiveness for cancers with that specific protein. These findings indicate that ABSK112 could be beneficial in treating certain types of lung cancer. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ABSK112

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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, 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06225804

NCT06225804 | A Study to Assess Safety, Tolerability, and ...

This is a first-in-human (FIH), multicenter, non-randomized, openlabel, phase 1 study of ABSK112 in patients with NSCLC to evaluate the safety, tolerability, PK ...

2.

aacrjournals.org

aacrjournals.org/cancerres/article/85/8_Supplement_2/LB240/761785/Abstract-LB240-Preclinical-evaluation-of-ABSK112-a

Abstract LB240: Preclinical evaluation of ABSK112, a ...

Nerve Damage in Tumors Reduces Immunotherapy Efficacy · Basal Origin Linked to Lineage Plasticity in Small Cell Lung Cancer · View more recent ...

3.

withpower.com

withpower.com/trial/phase-1-carcinoma-non-small-cell-lung-2024-7b5a2

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 ...

4.

aacrjournals.org

aacrjournals.org/cancerres/article/83/8_Supplement/LB327/725308/Abstract-LB327-Discovery-and-characterization-of

Abstract LB327: Discovery and characterization of ABSK112 ...

In xenograft mouse models with various EGFR Exon20 mutations, oral dose of ABSK112 showed strong and dose-dependent anti-tumor efficacy.

5.

prnewswire.com

prnewswire.com/news-releases/2025-aacr--abbisko-therapeutics-presents-late-breaking-pre-clinical-research-results-on-absk112-egfr-exon20ins-absk131-prmt5mta-and-abk-kras-1-302439218.html

2025 AACR | Abbisko Therapeutics Presents Late ...

Our findings establish ABSK112 as a potent, selective and CNS-penetrant HER2 inhibitor, warranting further clinical evaluation of it as a ...

6.

clin.larvol.com

clin.larvol.com/trial-detail/NCT06225804

A Study to Assess Safety, Tolerability, and ...

... ABSK112 in Patients With Non-Small Cell Lung Cancer. P1. Abbisko Therapeutics Co, Ltd. N=164. Recruiting. NA. Outcome Timelines (2). Primary. Outcome Measure ...

7.

synapse.patsnap.com

synapse.patsnap.com/drug/43a988513a67419b8da04453372c58b0

ABSK-112 - Drug Targets, Indications, Patents

A Phase 1, Open-Label Study of ABSK112 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Non-Small Cell Lung Cancer.