A Phase 2 Study of ABSK043 Combined With Osimertinib

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 7 центров

• The First Affiliated Hospital, Sun Yat-sen University — Гуанчжоу
• Harbin Medical University Cancer Hospital — Харбин
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• The First Hospital of China Medical University — Шэньян
• Shanghai Chest Hospital — Шанхай
• Shanxi Provincial Cancer Hospital — Taiyuan
• The First Affiliated Hospital, Zhejiang University School of Medicine — Ханчжоу

Идентификаторы

NCT: NCT07710612 · ABSK043-203

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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