A Phase 2 Study of ABSK043 Combined With Osimertinib

Official title

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

Overview

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

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.

Interventions

• 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.

Primary outcome measures

• - Incidence of dose-limiting toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Adverse events(AEs) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: From the time patients receive the first dose of study drug to 12 months，assessed up to 5 years.]

Secondary outcome measures (12)

• Maximum observed concentration（Cmax） [Time frame: 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) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Elimination half-life(t1/2) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Apparent volume of distribution(Vz/F) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Apparent oral clearance(CL/F) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Maximum observed concentration after multiple doses(Cmax,ss) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Minimum observed concentration after multiple doses(Cmin,ss) [Time frame: 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) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Accumulation ratio(AR) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Time to maximum observed concentration(tmax) [Time frame: From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.]
• Progression-Free Survival (PFS) [Time frame: From treatment start up to 5 years]
• Objective response rate (ORR) [Time frame: From treatment start up to 5 years]

Eligibility criteria

Inclusion Criteria：

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

Dose escalation and backfill cohorts:

• 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.
• Participants must have received ≥2 prior lines of frontline systemic therapy.
• Documented or central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
• Documented genetic testing report confirms the presence of EGFR alteration(s) in tumor or plasma.

Expansion cohort(s):

• Participants must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting for locally advanced or metastatic disease.
• Central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
• Documented genetic testing reports confirm the presence of EGFR
• Presence of at least one measurable tumor lesion
• ECOG score 0-1 at screening.
• 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.

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 · 7 centers

• The First Affiliated Hospital, Sun Yat-sen University — Guangzhou
• Harbin Medical University Cancer Hospital — Harbin
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• The First Hospital of China Medical University — Shenyang
• Shanghai Chest Hospital — Shanghai
• Shanxi Provincial Cancer Hospital — Taiyuan
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07710612 · ABSK043-203

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗