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

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

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, and preliminary antitumor efficacy.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: ABSK112

Detailed Description

The study will be started with a dose escalation part of ABSK112 administered in repeated 28-day cycles in patients with NSCLC. The expansion part of oral ABSK112 at the recommended dose of expansion (RDE) will be followed to evaluate safety, tolerability, and preliminary antitumor activity among patients with locally advanced or metastatic NSCLC harboring EGFR Exon20ins.

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: YUAN LU; Phone Number: +86-21-68910052; Email: clinical@abbisko.cn
• Study Contact Backup: Name: Yinan Lin; Phone Number: +86-21-68910052; Email: yinan.lin@abbisk.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • Anhui Chest Hospital
      • Contact: Rui Wang
      • Principal Investigator: Rui Wang
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Principal Investigator: Zhiyong He
      • Contact: Zhiyong He
  • Harbin
    • Xi'an, Harbin, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Yu Yao
      • Principal Investigator: Yu Yao
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: yan Yu
      • Principal Investigator: Yan Yu
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Cancer Hospital
      • Principal Investigator: Qiming Wang
      • Contact: Qiming Wang
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital Tongji Medical College Huzhong University of Science and Techology
      • Contact: Xiaorong Dong
      • Principal Investigator: Xiaorong Dong
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Principal Investigator: Lin Wu
      • Contact: Lin Wu
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Longhua Sun
      • Principal Investigator: Longhua Sun
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • Jilin Cancer Hospital
      • Principal Investigator: Ying Cheng
      • Contact: Ying Cheng
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Central Hospital Affiliated to Shangdong of First Medical University
      • Principal Investigator: Qing Wen
      • Contact: Meili Pan
      • Principal Investigator: Meili Pan
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Shun Lu
      • Contact: Shun Lu
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • Sichuan Cancer Hospital
      • Principal Investigator: Wenxiu Yao
      • Contact: Wenxiu Yao
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Caner Hospital
      • Principal Investigator: Zhengbo Song
      • Contact: Zhengbo Song
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Recruiting
      • Precision NextGen Oncology
      • Principal Investigator: Kamlesh Sankhala, MD
      • Contact: Kamlesh Sankhala, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ABSK112; 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.

Drug: ABSK112; In the escalation part, patients will receive a single dose of oral ABSK112 on Cycle1 Day1 only, and then patients will continuously receive ABSK112 once daily (QD) or twice daily (BID) in subsequent cycles. In the expansion part, patients will each be treated at the selected RDE dose level.; Other Names: EGFR Exon20 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT	Dose-limiting toxicities	from Day1 to Day28
AEs	Adverse events	The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months.
AESIs	Adverse events of special interest (AESIs)	The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months.
SAEs	Serious adverse events (SAEs)	The date of signing the informed consent form until 30 days (including Day 30) after the last dose of study drug, assessed up to 50 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed concentration	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
AUC	area under the concentration-time curve	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
t1/2	elimination half-life	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
Vz/F	apparent volume of distribution	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
CL/F	apparent oral clearance	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
Cmax,ss	maximum observed concentration after multiple doses	From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months
Cmin,ss	minimum observed concentration after multiple doses	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
AUCtau,ss	area under the concentration-time curve after multiple doses	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
AR	accumulation ratio	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
tmax	time to maximum observed concentration	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
ORR	Objective response rate	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
DOR	Duration of response	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
PFS	Progression-free survival	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
DCR	Disease control rate	From date of enrollment（Day1）until the date of disease progression, start of new anticancer treatment, death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 50 months.
OS	Overall survival	From date of enrollment（Day1）until the date of death, withdrawal of consent of study, lost to follow up or end of study, whichever comes first，assessed up to 100 months.

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ABSK112-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No