A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC)

Официальное название

An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumour Activity of Novel Combinations in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (LIBRA)

Обзор

This is a Phase II, multi-center, open-label platform study evaluating novel combination treatment options in participants with locally advanced or metastatic NSCLC. The study will consist of several sub-studies, each evaluating the safety, tolerability, and preliminary antitumour activity of various treatment combinations. This study will be conducted in approximately 80 centers globally across 10 countries.

Подробное описание

The master protocol will include 3 sub-studies, each focused on a specific disease population.

* Sub-study 1 will investigate rilvegostomig± ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 ≥50%. * Sub-study 2 will investigate rilvegostomig + ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 1-49%. * Sub-study 3 will investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+

Each sub-study may include 2 parts (unless stated in the individual sub study protocols): Part A: one or more Safety Run-in cohort(s), and Part B: one or more Dose Expansion cohort(s).

Вмешательства

• Препарат Rilvegostomig
  Rilvegostomig will be administered as IV infusion.
• Препарат Ramucirumab
  Ramucirumab will be administered as IV infusion.
• Препарат Dato-DXd
  Dato-DXd will be administered as IV infusion.

Первичные конечные точки

• Number of participants with adverse events (AE) and serious adverse events (SAE) [Срок оценки: Through study completion, an average of 3 years]
• Objective response rate (ORR) [Срок оценки: Through study completion, an average of 3 years]

Вторичные конечные точки (9)

• Best Overall Response(BOR) [Срок оценки: Through study completion, an average of 3 years]
• Change in Target Lesion Tumor Size [Срок оценки: Through study completion, an average of 3 years]
• Progression free survival (PFS) [Срок оценки: Through study completion, an average of 3 years]
• Disease Control Rate(DCR) at 12 Weeks [Срок оценки: From Day 1 pre-dose to 12 weeks]
• Duration Of Response (DoR) [Срок оценки: Through study completion, an average of 3 years]
• Overall Survival(OS) [Срок оценки: Through study completion, an average of 3 years]
• Serum concentration [Срок оценки: Through study completion, an average of 3 years]
• Maximum plasma drug concentration (Cmax) [Срок оценки: Through study completion, an average of 3 years]
• Immunogenicity of study interventions in participants receiving treatment [Срок оценки: Through study completion, an average of 3 years]

Критерии участия

Inclusion Criteria for All Sub-studies:

• Participant must be ≥ 18 years of age at the time of signing the ICF
• WHO/ECOG performance status of 0 or 1
• At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline.
• Adequate bone marrow and organ function
• Life expectancy ≥ 12 weeks
• Provision of acceptable tumour tissue

Specific Inclusion Criteria for Sub-Study 1 and Sub-Study 2:

• Histologically or cytologically documented advanced or metastatic NSCLC
• PD-L1 TC ≥ 1% (TC≥ 50% for sub-study 1, 1-49% for sub-study 2)
• Absence of sensitizing EGFR mutations or ALK rearrangements. No known other Actionable Genomic Alterations(AGAs)

Specific Inclusion Criteria for Sub-Study 3:

• Histologically or cytologically documented advanced or metastatic non-squamous NSCLC
• Documented positive AGA and had progressed on prior targeted therapy

Exclusion Criteria for All Sub-studies:

• As judged by the investigator, any severe or uncontrolled systemic diseases, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
• Active or prior documented autoimmune or inflammatory disorders
• Persistent toxicities (CTCAE Grade ≥ 2) (NCI CTCAE v5.0) caused by previous anti cancer therapy, excluding alopecia.
• Spinal cord compression or leptomeningeal carcinomatosis for sub-study 1 and sub-study 2. Unstable spinal cord compression for sub-study 3
• Unstable brain metastases
• History of another primary malignancy.
• Active infection, including TB and infections with HIV, HBV (verified by known positive HBsAg result), HCV.
• Uncontrolled or significant cardiac disease
• Receipt of prior systemic chemotherapy/chemoradiation/immunotherapy for advanced NSCLC for sub-study 1 and sub-study 2.
• Prior exposure to immune-mediated therapy
• History of uncontrolled hypertension, and active bleeding diseases, and high risks of bleeding and disorders of coagulation
• Any concurrent anti-cancer treatment.
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 19 центров

• Research Site — Чанша
• Research Site — Чэнду
• Research Site — Deyang
• Research Site — Дунгуань
• Research Site — Фучжоу
• Research Site — Гуанчжоу
• Research Site — Гуанчжоу
• Research Site — Ханчжоу
• … и ещё 11 центров

Япония · 11 центров

• Research Site — Bunkyō City
• Research Site — Fukuyama-shi
• Research Site — Kobe
• Research Site — Kurume-shi
• Research Site — Kyoto
• Research Site — Kyoto
• Research Site — Osaka
• Research Site — Sakaishi
• … и ещё 3 центра

South Korea · 9 центров

• Research Site — Cheongju-si
• Research Site — Namdong-gu
• Research Site — Seongnam-si
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Suwon
• … и ещё 1 центр

Тайвань · 9 центров

• Research Site — Liuying
• Research Site — Taichung
• Research Site — Taichung
• Research Site — Tainan
• Research Site — Tainan
• Research Site — Taipei
• Research Site — Taipei
• Research Site — Taipei
• … и ещё 1 центр

Италия · 8 центров

• Research Site — Aviano
• Research Site — Catania
• Research Site — Meldola
• Research Site — Milan
• Research Site — Milan
• Research Site — Orbassano
• Research Site — Roma
• Research Site — Rozzano

США · 6 центров

• Research Site — Santa Monica
• Research Site — Santa Rosa
• Research Site — Atlanta
• Research Site — Baltimore
• Research Site — Houston
• Research Site — Fairfax

Испания · 6 центров

• Research Site — A Coruña
• Research Site — Madrid
• Research Site — Manresa
• Research Site — Málaga
• Research Site — Santander
• Research Site — Valencia

Франция · 5 центров

• Research Site — Avignon
• Research Site — Paris
• Research Site — Rennes
• Research Site — Saint-Herblain
• Research Site — Suresnes

Таиланд · 4 центра

• Research Site — Bangkok
• … и ещё 3 центра

Австралия · 3 центра

• Research Site — Heidelberg
• Research Site — Nedlands
• Research Site — Woodville

Сингапур · 2 центра

• Research Site — Singapore
• Research Site — Singapore

Канада · 1 центр

• Research Site — Toronto

Идентификаторы

NCT: NCT07098338 · D6187C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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