Assessing the safety and effectiveness of ABSK112 for lung cancer patients

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

This study is testing a new drug called ABSK112 to see if it is safe and effective for people with advanced lung cancer that has certain genetic changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 164 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abbisko Therapeutics Co, Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 14 sites (Beverly Hills, California and 13 other locations)
• Trial ID: NCT06225804 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, multicenter, non-randomized, open-label phase 1 study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of ABSK112 in patients with non-small cell lung cancer (NSCLC). The study will begin with a dose escalation phase, followed by an expansion phase at the recommended dose of ABSK112 for patients with locally advanced or metastatic NSCLC that have specific EGFR mutations. Participants will receive ABSK112 in repeated 28-day cycles, and the study aims to gather data on its effects and safety profile.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed locally advanced or metastatic NSCLC and specific EGFR exon 20 insertion mutations.

Not a fit: Patients who do not have the specified EGFR mutations or those who are not candidates for the study due to other health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced non-small cell lung cancer who have limited therapeutic alternatives.

How similar studies have performed: Other studies targeting similar mutations in lung cancer have shown promise, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients should understand, sign, and date the written informed consent form prior to screening.
2. Male or female aged 18 years or older.
3. Patients with histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC.
4. Cohort-specific inclusion criteria:

   1. For the escalation part (except for the RDE confirmation part), patients have progressed on, rejected, or are intolerant of standard therapy, or for whom no standard therapy exists
   2. For RDE confirmation in the escalation part: same as Cohort 1 in the expansion part
   3. For the expansion part, patients have documented EGFR in-frame exon 20 insertion mutations confirmed by certificated local laboratories; and must also meet all criteria for the cohort in which their entry is proposed.
5. Patients must have at least one measurable target lesion according to RECIST v1.1
6. ECOG performance status 0 or 1
7. 7\. Life expectancy ≥3 months
8. Adequate organ function and bone marrow function.
9. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits
10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle1 Day1.
11. For patients participating in food effect exploration part:

    1. Be able to eat a standardized high-fat meal within 30 minutes
    2. Be able to fast for 10 hours.
12. Non-surgically sterilized male or female patients of childbearing potential must agree to use highly effective methods of birth control during the study treatment and for approximately 6 months after the last dose of study drug. A condom is also required to be used by vasectomized men to prevent delivery of the drug via seminal fluid.

Exclusion Criteria:

1. Known allergy or hypersensitivity to any component of the investigational product.
2. NSCLC patients with EGFR Cys797Ser (C797S) mutation.
3. Cohort-specific exclusion criteria.
4. Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
5. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction, or current evidence of GI disease that present with diarrhea. If any of these conditions exist, the sites' staff should discuss with the sponsor to determine patient eligibility.
6. Previous anti-cancer therapy, including chemotherapy, radiotherapy, molecular targeted therapy, antibody therapy or other investigational drugs received ≤4 weeks prior to initiation of study treatment.
7. Major surgery within 4 weeks prior to the first dose of study drug. Or any surgical wound is infected, dehisced, or not completely healed before the screening.
8. Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade ≤1 severity (CTCAE v5.0) with the exception of which eligibility criteria allows, or alopecia, vitiligo, hypothyroidism stable on hormone replacement, or Grade 2 peripheral neurotoxicity.

   Note: Refer to inclusion criteria regarding hypertension.
9. Potent moderate and strong inhibitors or inducers of CYP3A family within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort); consumption of grapefruit juice, grapefruit hybrids, pomegranates, starfruits, pomelos, seville oranges or juice products within 3 days prior to the first dose of study treatment.
10. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
11. Impaired cardiac function or clinically significant cardiac disease.
12. Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody.
13. Exclusion of hepatitis infection based on the following results and/or criteria:

    1. Active hepatitis B infection: positive tests for hepatitis B surface antigen (HbsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient with positive tests for HbsAg or anti-HBc but with HBV-DNA measurements lower than detectable can be enrolled.
    2. Active hepatitis C infection: positive Hepatitis C virus antibody. If positive antibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. A patient with positive anti-HCV but with a negative test for HCV RNA can be enrolled.
14. Patients with ascites or pleural effusion, or pericardial effusion which is refractory/uncontrolled, or requiring the intervention within 2 weeks prior to the first dose.
15. Current evidence of radiation pneumonitis that required steroid treatment or unresolved drug-related pneumonitis, or current evidence or history of interstitial lung disease (ILD).
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to the start of study drug.
17. Vaccination with a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment except for administration of inactivate vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).
18. Current evidence or previous history of corneal pathology such as keratopathy, corneal abrasion or ulceration, or any other abnormal changes that may increase the risk of corneal toxicity during the study treatment
19. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of investigators, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
20. Planned major surgery during study treatment.

Where this trial is running

Beverly Hills, California and 13 other locations

• Precision NextGen Oncology — Beverly Hills, California, United States (Recruiting)
• Anhui Chest Hospital — Hefei, Anhui, China (Not_yet_recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• The first Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Harbin, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital Tongji Medical College Huzhong University of Science and Techology — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• The first Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Jilin Cancer Hospital — Changchun, Jilin, China (Not_yet_recruiting)
• Central Hospital Affiliated to Shangdong of First Medical University — Jinan, Shandong, China (Not_yet_recruiting)
• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Sichuan Cancer Hospital — Chengdu, Sichuan, China (Not_yet_recruiting)
• Zhejiang Caner Hospital — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Yuan Lu

Conditions Non-Small Cell Lung Cancer