ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors

Официальное название

Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers That Progressed on PD-1/PD-L1 Inhibitors

Обзор

The goal of this Phase 3 clinical trial is to study the safety and efficacy of the nextgen anti-CTLA-4 antibody, gotistobart (ONC-392/BNT316), in patients with metastatic non-small cell lung cancer who have disease progressed on anti-PD-1/PD-L1 antibody based therapy. The study will test whether gotistobart, in comparison with chemotherapy agent docetaxel, could prolong the life for NSCLC patients. Patients will be randomized to be treated with either gotistobart or docetaxel, IV infusion, once every 21 days, for up to 17 cycles in approximately one year.

Подробное описание

This is a seamless 2-stage, randomized, open-label, active-controlled, Phase 3 study. The study population consists of patients with NSCLC who progressed on PD-1/PD-L1 inhibitor. Approximately 630 patients will be enrolled.

Two gotistobart dosing regimens will be tested in Stage I, and one will be selected for Stage II.

Stage I, the dose-confirmation stage, will assess the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W.

Stage II will assess the safety and efficacy of gotistobart at the selected dosing regimen versus docetaxel on squamous cell NSCLC. Patients will be randomized 1:1 to receive either gotistobart at the selected dosing regimen or docetaxel.

Вмешательства

• Препарат Gotistobart
  Gotistobart will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.
• Препарат Docetaxel
  Docetaxel will be administrated through IV infusion over 60 minutes, once every 21 days in 75mg/m2 dose.

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: 36 months]

Вторичные конечные точки (3)

• Objective response rate (ORR) [Срок оценки: 36 months]
• Progression-free survival (PFS) [Срок оценки: 36 months]
• Treatment emergent adverse events, treatment related adverse events and immune related adverse events. [Срок оценки: 36 months]

Критерии участия

Inclusion Criteria (Major criteria):

• Adult (≥ 18 years), all genders, capable of signing informed consent.
• Histologically- or cytologically- confirmed diagnosis of metastatic squamous NSCLC, metastasis can be regional lymph nodes or distant organs.
• Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:

• At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy;
• Prior treatment with at least 2 cycles of a platinum-based chemotherapy, followed by at least 12 weeks of standard doses of PD-1 or PD-L1 inhibitor-based immunotherapy.

Antibodies against CTLA-4, LAG-3, TIGIT, VEGF or VEGFR in combination with PD-1/PD-L1 inhibitor are allowed.

• At least one measurable tumor lesion according to RECIST 1.1.
• ECOG score of 0 or 1.
• Adequate organ functions. Serum LDH level ≤ 2xULN.
• Life expectancy ≥ 3 months.

Exclusion Criteria (Major criteria):

• Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
• Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
• Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
• Having documented actionable mutations or genomic alterations in any of the following genes: EGFR, ALK, ROS1, HER2, MET, BRAF, RET or NTRK;. Exception: KRAS mutations are not excluded.
• Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
• Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
• Active interstitial lung disease (ILD) or non-infectious pneumonitis.
• Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
• Impaired heart function.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 46 центров

• XCancer/Dothan Hematology & Oncology - 1114 — Dothan
• Genesis Cancer and Blood Institute - 1123 — Russellville
• The Oncology Institute (TOI) Clinical Research - 1109 — Cerritos
• Emad Ibrahim MD Inc. - 1147 — Redlands
• UC Davis Comprehensive Cancer Center - 1103 — Sacramento
• Bass Medical Group - 1155 — Walnut Creek
• Nuvance Health - 1118 — Norwalk
• D&H Cancer Research Center LLC - 1153 — Margate
• … и ещё 38 центров

Китай · 40 центров

• The First Affiliated Hospital of Anhui Medical University - 3221 — Хэфэй
• Anhui Medical University - The Second Hospital - 3222 — Хэфэй
• Beijing Cancer Hospital - 3205 — Пекин
• Cancer Hospital, Chinese Academy of Medical Sciences - 3211 — Пекин
• Fujian Medical University Union Hospital - 3225 — Фучжоу
• The First Affiliated Hospital of Xiamen University - 3210 — Xiamen
• Dongguan People's Hospital - 3206 — Дунгуань
• Guangdong Provincial People's Hospital - 3201 — Гуанчжоу
• … и ещё 32 центра

Turkey (Türkiye) · 12 центров

Список центров уточняется — проверьте первичный протокол.

Италия · 11 центров

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Великобритания · 10 центров

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South Korea · 7 центров

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Германия · 6 центров

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Испания · 6 центров

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Австралия · 4 центра

• Bankstown Hospital - 3305 — Bankstown
• Mater - 3301 — Newstead
• Cancer Research SA - 3303 — Adelaide
• Western Health - Sunshine Hospital - 3307 — St Albans

Бельгия · 4 центра

• AZ Maria Middelares - 2104 — Ghent
• Jessa Ziekenhuis (Jessa Hospital) - Campus Salvator - 2102 — Hasselt
• C. H. R. de la Citadelle - 2103 — Liège
• Vitaz - Sint-niklaas Moerland - 2101 — Sint-Niklaas

Канада · 3 центра

• BC Cancer Centre - Kelowna - 1203 — Kelowna
• Saskatchewan Cancer Agency - Regina - 1201 — Regina
• Saskatchewan Cancer Agency - Saskatoon Cancer Centre - 1202 — Saskatoon

Нидерланды · 3 центра

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Публикации

• Zhang Y, Du X, Liu M, Tang F, Zhang P, Ai C, Fields JK, Sundberg EJ, Latinovic OS, Devenport M, Zheng P, Liu Y. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019 Aug;29(8):609-627. doi: 10.1038/s41422-019-0184-1. Epub 2019 Jul 2. PMID 31267017
• Liu Y, Zheng P. Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy. Trends Pharmacol Sci. 2020 Jan;41(1):4-12. doi: 10.1016/j.tips.2019.11.003. Epub 2019 Dec 10. PMID 31836191
• Cho BC, Balaraman R, Chen HJ, Yu X, Fawole A, Liu ZG, Zhang J, Wu L, Yang B, Leddon JL, Hamm J, Huang Y, Wu L, Pan P, Singh P, Beardsley A, Kayali F, Davarifar A, Lee KH, Park KU, Lee Y, Li L, Wang X, Sun M, Yu Y, Jain V, Shpyro S, Wang Q, Wenger M, Sahin U, Efuni S, Song S, He K, Zheng P, Liu Y, He K, Li T, Socinski MA, Wu YL. Gotistobart or docetaxel in metastatic squamous non-small cell lung ca PMID 41896648

Идентификаторы

NCT: NCT05671510 · PRESERVE-003 · 2023-505311-20-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗