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

NCT06225804 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ABSK112-101
• Study Type: interventional
• Target: 164
• Locations: 2 countries
• Sites: 14

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (15)

• Cmax

  From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months

• AUC

  From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months

• t1/2

  From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months

• Vz/F

  From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months

• CL/F

  From date of enrollment（Day1） until the date of end of treatment visit, assessed up to 50 months

Study Arms (1)

ABSK112

EXPERIMENTAL

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

Interventions

ABSK112 DRUG

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.

Also known as: EGFR Exon20 inhibitor

ABSK112

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should understand, sign, and date the written informed consent form prior to screening.
• Male or female aged 18 years or older.
• Patients with histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC.
• 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
• For RDE confirmation in the escalation part: same as Cohort 1 in the expansion part
• 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.
• Patients must have at least one measurable target lesion according to RECIST v1.1
• ECOG performance status 0 or 1
• \. Life expectancy ≥3 months
• Adequate organ function and bone marrow function.
• Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits
• 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.
• For patients participating in food effect exploration part:
• Be able to eat a standardized high-fat meal within 30 minutes
• Be able to fast for 10 hours.

You may not qualify if:

• Known allergy or hypersensitivity to any component of the investigational product.
• NSCLC patients with EGFR Cys797Ser (C797S) mutation.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
• Impaired cardiac function or clinically significant cardiac disease.
• Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody.
• 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.
• 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.
• 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.
• Current evidence of radiation pneumonitis that required steroid treatment or unresolved drug-related pneumonitis, or current evidence or history of interstitial lung disease (ILD).

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (14)

Precision NextGen Oncology

Beverly Hills, California, 90212, 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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yuan Lu

CONTACT

+86-21-68910052; clinical@abbisko.cn

Yinan Lin

CONTACT

+86-21-68910052; yinan.lin@abbisk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 26, 2024
• Study Start: February 22, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 18, 2024

Record last verified: 2024-03

Locations

CN (13); US (1)