A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Glecirasib
An Open-label Phase II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of ABSK043 in Combination With Glecirasib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring a KRAS G12C Mutation
1 other identifier
interventional
86
1 country
17
Brief Summary
This is a multicenter, open-label phase 2 study that will enroll KRASG12C mutated patients with locally advanced or metastatic NSCLC, receiving treatment (ABSK043 in combination with Glecirasib) in a 21-day combination cycle.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 nonsmall-cell-lung-cancer
Started Oct 2025
Typical duration for phase_2 nonsmall-cell-lung-cancer
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 2, 2025
CompletedFirst Posted
Study publicly available on registry
September 10, 2025
CompletedStudy Start
First participant enrolled
October 25, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 30, 2029
September 10, 2025
September 1, 2025
3.2 years
September 2, 2025
September 8, 2025
Conditions
Outcome Measures
Primary Outcomes (5)
Incidence of DLT
Dose-limiting toxicities
At the end of Cycle 1 (each cycle is 21 days)
AEs
Adverse events
From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
SAEs
Serious adverse events (SAEs)
From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
AESIs AESIs
Adverse events of special interest (AESIs)
From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
ORR
objective response rate
From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.
Secondary Outcomes (15)
Cmax
From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months
AUC
From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
t1/2 t1/2
From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Vz/F
From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
CL/F
From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
- +10 more secondary outcomes
Study Arms (1)
Experimental: ABSK043 in combination with Glecirasib
EXPERIMENTALThis is an open-label phase 2 study with an escalation part and an expansion part. • Escalation Part: up to 50 previously treated patients with KRASG12C mutation. Does Escalation Cohort(Part A): up to 30previously treated patients with KRASG12C mutation. Dose Confirmation Cohort(Part B): up to 20previously treated patients with KRASG12C mutation. • Expansion Part: up to 36 treatment-naïve patients with KRASG12C mutation.
Interventions
Dose escalation cohort( Part A) ABSK043 150 mg BID in combination with Glecirasib 200 mg QD will be selected as the starting dose. Based on the accumulated safety data and PK profile, the Safety Review Committee (SRC), composed of the investigator and the sponsor, may discuss and agree to allow exploration of other possible doses. Dose confirmation cohort (Part B) and Expansion cohort Patients in dose confirmation cohort and expansion cohort will receive the recommended dose in dose escalation cohort and be evaluated for safety and preliminary anti-tumor activity. All patients will continue to receive combination therapy every 21 days until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator decision to discontinue treatment, or end of the study.
Eligibility Criteria
You may qualify if:
- Prior to any protocol- specific procedures are performed, the patient should understand and voluntarily sign and date the written informed consent form.
- Gender was not limited patients aged ≥18 years at the time of signing the informed consent.
- Histologically or cytologically confirmed locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC).
- For patients in the dose-escalation cohort (Part A) of the escalation part:
- Patients must have experienced disease progression following at least one line of prior standard systemic therapy, but no more than two lines of systemic therapy.
- For patients in the dose confirmation cohort (Part B) of the escalation part :
- Prior treatment requirements for patients in cohort (Part B) are the same as those for patients in (Part A);
- Documented or central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .
- For patients in the expansion cohort of the expansion part :
- Patients who have not received prior systemic therapy for locally advanced or unresectable/metastatic disease;
- Central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .
- Tumor tissue or blood test report confirmed KRASG12C mutation.
- Patients must have at least one measurable lesion as defined by RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0\~1.
- Expected survival time of ≥3 months.
- +1 more criteria
You may not qualify if:
- Histological or cytological evidence of small cell lung cancer or neuroendocrine carcinoma components.
- Toxicities from prior antitumor therapy have not returned to baseline or stabilized.
- Patients with active brain metastases.
- The patient currently has active interstitial lung disease.
- Patients currently have active autoimmune disease or a history of autoimmune disease that may be at risk for recurrence.
- Any condition requiring systemic treatment with corticosteroids.
- Uncontrolled or significant cardiovascular disease.
- Has a known human immunodeficiency virus (HIV) infection that is not well controlled.
- Any evidence of severe or uncontrolled diseases or other factors which in the Investigator's opinion makes it undesirable for the patients to participate in the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
Fujian Cancer Hospital
Fuzhou, Fujian, China
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
Guangxi Medical University Cancer Hospital & Guangxi Cancer Institude
Nanning, Guangxi, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Tongji Hospital Tongji Medical College of Hust
Wuhan, Hubei, China
Hunan Cancer Hospitial
Changsha, Hunan, China
Zhongda Hospital Southeast University
Nanjing, Jiangsu, China
The First Hospital of China Medical University
Shenyang, Liaoning, China
Central Hospital Affiliated to Shangdong First Medical University
Jinan, Shangdong, China
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, China
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, China
West China Hospital Sichuan University
Chengdu, Sichuan, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 2, 2025
First Posted
September 10, 2025
Study Start
October 25, 2025
Primary Completion (Estimated)
December 30, 2028
Study Completion (Estimated)
July 30, 2029
Last Updated
September 10, 2025
Record last verified: 2025-09