ABSK112 for Lung Cancer
Recruiting in Palo Alto (17 mi)
+13 other locations
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.
12345What 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.
678910Eligibility 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.
+12 more
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.
+17 more
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: ABSK112Experimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Precision NextGen OncologyBeverly Hills, CA
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Who Is Running the Clinical Trial?
Abbisko Therapeutics Co, LtdLead Sponsor
References
Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. [2021]The oncogenic property of anaplastic lymphoma kinase (ALK) plays an essential role in the pathogenesis of various cancers and serves as an important therapeutic target. In this study, we identified frequent intragenic loss of heterozygosity and six novel driver mutations within ALK in lung adenocarcinomas. Overexpression of H694R or E1384K mutant ALK leads to hyperphosphorylation of ALK, and activation of its downstream mediators STAT3, AKT, and ERK resulted in enhanced cell proliferation, colony formation, cell migration, and tumor growth in xenograft models. Furthermore, the activated phospho-Y1604 ALK was increasingly detected in 13 human lung cancer cell lines and 263 lung cancer specimens regardless of tumor stages and types. Treatment of two different ALK inhibitors, WHI-P154 and NVP-TAE684, resulted in the down-regulation of aberrant ALK signaling, shrinkage of tumor, and suppression of metastasis and significantly improved survival of ALK mutant-bearing mice. Together, we identified that novel ALK point mutations possessed tumorigenic effects mainly through hyperphosphorylation of Y1604 and activation of downstream oncogenic signaling. The upregulated phospho-Y1604 ALK could serve as a diagnostic biomarker for lung cancer. Furthermore, targeting oncogenic mutant ALKs with inhibitors could be a promising strategy to improve the therapeutic efficacy of fatal lung cancers.
First-line treatment of advanced non-small cell lung cancer with ALK rearrangement: state of the art and future development. [2022]Introduction: Approximately 5% of all diagnosed non-small cell lung cancer (NSCLC) patients harbor a genetic rearrangement between the ALK and EML4 genes, representing a specific molecular, histological and clinical subgroup (ALK+ NSCLC). To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results. However, all treated patients eventually develop acquired resistance mechanisms to these agents (mainly resistance mutations) and experience progression of the disease.Areas covered: This paper provides a comprehensive state-of-the-art review about first-line approved ALK-TKIs, furthermore, it discusses the most promising ALK-TKIs under development designed to overcome resistance mutations and their implications.Expert opinion: Alectinib should currently be regarded as the standard of care for the first-line treatment of ALK+ NSCLC, considering its superior efficacy and safety profile. Regarding developing agents, lorlatinib and ensartinib appear to be the most promising ones, even though the data from their trials are still immature.
Effective Crizotinib schedule for an elderly patient with ALK rearranged non-small-cell lung cancer: a case report. [2018]Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.
Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells. [2021]Although most non-small-cell lung cancer (NSCLC) patients with the echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene - benefit from ALK tyrosine kinase inhibitors (ALK-TKIs), the efficacy of these drugs varies greatly among individuals.
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]A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here.
Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS). [2022]Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are highly effective treatments for ALK-positive lung cancer. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS).
Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective for treatment of EGFR- or ALK-mutated lung cancer. Nevertheless, they are associated with several unique toxicities. Although the available US Food and Drug Administration (FDA)-approved drug label can provide guidance for safety monitoring, its integration into clinical practice has not been previously described. We studied the conduct of safety monitoring activity (SMA) at a large academic institution. On the basis of FDA-approved drug labels, two drug-specific SMAs were identified for osimertinib, crizotinib, alectinib, or lorlatinib. Electronic medical records of patients initiated on these drugs from 2017 to 2021 were retrospectively reviewed. Each course of treatment was evaluated for the occurrence of SMAs and the corresponding adverse events. Analyses included 130 treatment courses from 111 unique patients. For each SMA evaluated, the prevalence of SMA conduct ranged from 10.0% to 84.6%. The most frequently conducted SMA was ECG for lorlatinib therapy and the least was creatine phosphokinase analysis for alectinib. We observed none of the assessed SMAs being conducted in 41 treatment courses (31.5%). EGFR inhibitor predicted a higher likelihood of both SMAs being conducted than ALK inhibitors (P = .02). Serious, grade 3 or 4 adverse events were observed in 21 treatment courses (16.2%), including one grade 4 transaminitis related to alectinib. On the basis of our experience, the conduct of SMA was more challenging to implement for ALK inhibitor than for EGFR inhibitor. Clinicians should be vigilant and review the FDA-approved drug label before prescribing.
Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]Targeted therapies have revolutionized the treatment for many patients with non-small cell lung cancer (NSCLC). Multiple new oral targeted therapies have been approved in the last decade; however, their overall efficacy may be reduced by poor adherence, treatment interruptions, or dose reductions due to adverse events. Most institutions lack standard monitoring protocols for toxicities from these targeted agents. This review describes important adverse events observed in clinical trials and reported by the U.S. Food and Drug Administration for both currently approved and upcoming promising therapies in the treatment of NSCLC. These agents cause a range of toxicities, including dermatologic, gastroenteric, pulmonary, and cardiac toxicities. This review proposes protocols for routine monitoring of these adverse events, both prior to initiation of therapy and while on treatment.
The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. [2020]Background: A total of 2%-7% of non-small cell lung cancer (NSCLC) patients have anaplastic lymphoma kinase (ALK) mutations. At present, three or more generations of ALK inhibitors have been used for ALK-positive NSCLC treatment, including crizotinib, alectinib, ceritinib, and brigatinib. Although most adverse events (AEs) of ALK inhibitors are grades 1 to 2 and generally can be well tolerated, serious adverse events (SAEs) of ALK inhibitors lack data analysis, and the lung toxicity of ALK inhibitors needs attention. Thus, we performed this meta-analysis to evaluate the safety of ALK inhibitors, especially in terms of drug-related SAEs. Methods: A total of 19 studies from 4 databases (PubMed, Science Direct, ClinicalTrials.gov and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed with the STATA 14.0 software. We analyzed the incidences of total AEs, total SAEs and SAEs for different ALK inhibitors. Results: AEs of the ALK inhibitors occurred in almost all participants, and SAEs occurred in more than 20% of the participants. For ceritinib and brigatinib, SAEs occurred in more than 40% of the participants. Alectinib is most likely the safest of the two generations of ALK inhibitors. Generally, the ALK inhibitors showed significant lung toxicity. Conclusion: In conclusion, attention should be focused on ALK inhibitor-related SAEs, especially lung toxicity. According to this meta-analysis, alxectinib seems to be the safest ALK inhibitor. Physicians should focus on the related SAEs when prescribing ALK inhibitors.
Evaluation of Lung Toxicity Related to the Treatment With Alectinib Using a Pharmacovigilance Database. [2022]The anaplastic lymphoma kinase (ALK) inhibitor alectinib is recommended as a first-line treatment for ALK lung cancer. Interstitial lung disease is the most common adverse event leading to discontinuation of alectinib. The purpose of this study was to use the Japanese Adverse Drug Event Report database for the evaluation of incidence trends and timing of alectinib toxicity in the lungs.