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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Incidence of DLT [Срок оценки: At the end of Cycle 1 (each cycle is 21 days)]
• AEs [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Вторичные конечные точки (12)

• Cmax [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

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 · 17 центров

• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• Beijing Cancer Hospital — Пекин
• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• Fujian Cancer Hospital — Фучжоу
• The First Affiliated Hospital of Sun Yat-sen University — Гуанчжоу
• Guangxi Medical University Cancer Hospital & Guangxi Cancer Institude — Nanning
• Harbin Medical University Cancer Hospital — Харбин
• Henan Cancer Hospital — Чжэнчжоу
• … и ещё 9 центров

Идентификаторы

NCT: NCT07164170 · ABSK043-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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