A Phase 2 Study of ABSK043 Combined With Osimertinib

A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of ABSK043 Combined With Osimertinib in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This is a phase 2, open-Label study to evaluate the efficacy and safety of ABSK043 Combined with Osimertinib in participants with EGFR-Mutated locally advanced or metastatic Non-Small Cell Lung Cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer With EGFR-mutated and PD-L1 Positive
• Intervention / Treatment: Drug: ABSK043 in combination with Osimertinib

Detailed Description

This is an open-label study with an escalation part and an expansion part. The dose escalation part will evaluate the safety, tolerability of ABSK043 in combination with Osimertinib in previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC. The expansion part will evaluate the efficacy of ABSK043 in combination with Osimertinib as first-line treatment for participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC at the one or more recommended dose(s). The safety, tolerability, and PK profile of ABSK043 in combination with Osimertinib will also be further evaluated.

Escalation Part:

The escalation part includes dose escalation cohorts and backfill cohort(s), enrolling a sufficient number with previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC.

Expansion Part:

The expansion part will enroll a sufficient number with treatment-naïve participants with locally advanced or metastatic NSCLC harboring the EGFR mutation and PD-L1 positive expression.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zan Chen; Phone Number: +8613816094024; Email: zan.chen@abbisko.com

Study Locations

• China
  • Hangzhou, China
    • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Principal Investigator: Jianying Zhou, Doctor
    • Contact: Jianying Zhou, Doctor; Phone Number: +86571-87236876; Email: drzjy@163.com
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Kejing Tang, Doctor; Phone Number: +8620-87755766; Email: tangkejing@163.com
      • Principal Investigator: Kejing Tang, Doctor
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
      • Contact: Yanbin Zhao, Doctor; Phone Number: +8613904811741 +86451-86298000; Email: zhaoyb_gcp@126.com
      • Principal Investigator: Yanbin Zhao, Doctor
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Xiaorong Dong, Doctor
      • Contact: Xiaorong Dong, Doctor; Phone Number: +8613986252286 +8627-85728022; Email: xhzzdxr@126.com
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
      • Contact: Mingfang Zhao, Doctor; Phone Number: +8613644055129 +8624-83282888; Email: zhaomf618@126.com
      • Principal Investigator: Mingfang Zhao, Doctor
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Chest Hospital
      • Principal Investigator: Shun Lu, Doctor
      • Contact: Shun Lu, Doctor; Phone Number: +8613601813062 +8621-62821990; Email: shunlu_shchest@sina.com
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provincial Cancer Hospital
      • Contact: Wei Guo, Doctor; Phone Number: +86351-4881611; Email: guowei812@126.com
      • Principal Investigator: Wei Guo, Doctor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria：

1. Aged 18 or above, male or female.
2. Participants must understand and voluntarily participate in this study and must have been provided informed consent for study participation.
3. NSNLC confirmed by tissue or cytological pathology. NSCLC with a mixed histology is eligible, if adenocarcinoma is the predominant histology.
4. Diagnosed locally advanced or metastatic NSCLC

5. Different requirements for specific cohort:

   Dose escalation and backfill cohorts:

   1. Participants with disease in the adjuvant setting, post chemoradiotherapy setting, locally advanced stage or metastatic stage, who have received at least one prior line of third-generation EGFR-TKI-based monotherapy or combination therapy and experienced disease progression.
   2. Participants must have received ≥2 prior lines of frontline systemic therapy.
   3. Documented or central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
   4. Documented genetic testing report confirms the presence of EGFR alteration(s) in tumor or plasma.

   Expansion cohort(s):

   1. Participants must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting for locally advanced or metastatic disease.
   2. Central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
   3. Documented genetic testing reports confirm the presence of EGFR
6. Presence of at least one measurable tumor lesion
7. ECOG score 0-1 at screening.
8. The expected life expectancy after the first dose is >12 weeks.

Exclusion Criteria:

• 1. Histological or cytological examinations suggest that NSCLC squamous cells is the predominant histology, or contains small cell lung cancer, neuroendocrine carcinoma, etc.

  2. Has a history of interstitial lung disease (ILD)/pneumonitis or active ILD 3. Spinal cord compression and unstable brain metastases. 4.Any unresolved toxicities from prior systemic therapy greater than CTCAE v6.0 Grade 1 at the time of starting study treatment.

  5. Participants with obvious and unstable pleural effusion, peritoneal effusion or pericardial effusion .

  6. Has a history of other malignant tumors, or currently have other malignant tumors.

  7. Participants with known HIV infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ABSK043 in combination with Osimertinib; This is an open-label phase 2 study with an escalation part and an expansion part.

Drug: ABSK043 in combination with Osimertinib; Three potential dose levels of ABSK043 are prespecified, and Osimertinib will be administered orally at a fixed dose of 80 mg QD in escalation cohort. Patients in dose confirmation cohort and dose expansion cohort will receive the recommended dose in dose escalation cohort and be evaluated for safety and preliminary anti-tumor activity of the combination therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- Incidence of dose-limiting toxicity (DLT)	Escalation Part	At the end of Cycle 1 (each cycle is 21 days)
Adverse events(AEs)	Escalation Part	From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Serious adverse events (SAEs)	Escalation Part	From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Adverse events of special interest (AESIs)	Escalation Part	From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Progression-free survival at 12 month	Expansion Part	From the time patients receive the first dose of study drug to 12 months，assessed up to 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration（Cmax）	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve (AUC)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Elimination half-life(t1/2)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Apparent volume of distribution(Vz/F)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Apparent oral clearance(CL/F)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Maximum observed concentration after multiple doses(Cmax,ss)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Minimum observed concentration after multiple doses(Cmin,ss)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Area under the concentration-time curve after multiple doses(AUCtau,ss)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Accumulation ratio(AR)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Time to maximum observed concentration(tmax)	Escalation Part	From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.
Progression-Free Survival (PFS)	Escalation Part	From treatment start up to 5 years
Objective response rate (ORR)	Defined as the proportion of participants achieving confirmed complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST v1.1.	From treatment start up to 5 years
Duration of response (DOR)	Defined as the time (months) from the first documented objective response to the investigator-assessed radiographic disease progression (PD) according to RECIST v1.1 or death from any cause, whichever occurs first.	From treatment start up to 5 years
Disease control rate (DCR)	Defined as the proportion of participants achieving confirmed complete remission (CR) or partial remission (PR), or stable disease (SD), as assessed by the investigator according to RECIST v1.1.	From treatment start up to 5 years
Time to progression (TTP)	Defined as the time (months) from the first dose of study drug until the onset of radiographic disease progression (PD) as assessed by the investigator according to RECIST v1.1.	From treatment start up to 5 years
Overall survival (OS)	Defined as the time (months) from the first administration of study drug to death due to any cause.	From treatment start up to 7 years

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: osimertinib
• Other Study ID Numbers: ABSK043-203

Drug and device information, study documents

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