A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Glecirasib

Official title

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

Overview

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.

Detailed description

The study consists of an escalation part and an expansion part. The escalation part will evaluate the safety, tolerability, preliminary efficacy, and PK profile of different doses of ABSK043 in combination with Glecirasib, and the combination regimen recommended for the expansion part. The expansion part will further evaluate the safety, PK profile, and anti-tumor efficacy of ABSK043 in combination with Glecirasib at the one or more recommended dose (s).

Up to 86 patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) are planned to be enrolled in the study.

* Escalation Part: up to 50 previously treated patients with KRASG12C mutation. * Expansion Part: up to 36 treatment-naïve patients with KRASG12C mutation.

Interventions

• Drug ABSK043 in combination with Glecirasib
  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

Primary outcome measures

• Incidence of DLT [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• AEs [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 outcome measures (12)

• Cmax [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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.]
• Cmax,ss [Time frame: 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.]
• Cmin,ss [Time frame: 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.]
• AUCtau,ss [Time frame: 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.]
• AR [Time frame: 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.]
• tmax [Time frame: 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.]
• DOR DOR [Time frame: 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.]
• PFS [Time frame: 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.]

Eligibility criteria

Inclusion criteria

• 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.
• Patients must have adequate organ and bone marrow function.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 17 centers

• The First Affiliated Hospital of Anhui Medical University — Hefei
• Beijing Cancer Hospital — Beijing
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Fujian Cancer Hospital — Fuzhou
• The First Affiliated Hospital of Sun Yat-sen University — Guangzhou
• Guangxi Medical University Cancer Hospital & Guangxi Cancer Institude — Nanning
• Harbin Medical University Cancer Hospital — Harbin
• Henan Cancer Hospital — Zhengzhou
• … and 9 more centers

Identifiers

NCT: NCT07164170 · ABSK043-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗