A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma

Официальное название

A Randomized, Phase 2/3, Open-Label Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab Versus Ipilimumab in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma

Обзор

The purpose of this study is to measure the clinical benefits of the combination of RP2 and nivolumab as compared with the combination of nivolumab and ipilimumab in patients with metastatic uveal melanoma who have not been treated with immune checkpoint inhibitor therapy.

Вмешательства

• Биопрепарат RP2
  Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.
• Биопрепарат Ipilimumab
  Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody
• Биопрепарат Nivolumab
  Nivolumab: Anti-PD-1 Monoclonal antibody

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: From Day 1 up to 3 years after last dose.]
• Progression Free Survival (PFS) [Срок оценки: From Day 1 up to 3 years after last dose.]

Вторичные конечные точки (3)

• Number of patients with treatment-emergent adverse events (TEAEs) [Срок оценки: From first dose up to 100 days after last dose.]
• Overall Response Rate (ORR) [Срок оценки: Every 12 weeks from Day 1 up to 3 years after last dose.]
• Disease Control Rate (DCR) [Срок оценки: Every 12 weeks from Day 1 up to 3 years after last dose.]

Критерии участия

Критерии включения

• Patients who are 18 years of age or older at the time of signed informed consent.
• Patients with confirmed diagnosis of metastatic Uveal melanoma not amenable to surgical resection.
• Has at least 1 measurable and injectable tumor of ≥ 1 cm in longest diameter (≥ 1.5 cm in the shortest axis for a lymph node \[LN\]) that is amenable to serial RP2 injections.
• Must be willing to provide tumor biopsy samples.
• LDH ≤ 2 × upper limit of normal (ULN).
• Has adequate hematologic, hepatic and renal function
• Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Life expectancy of > 6 months as estimated by the Investigator.

Критерии исключения

• Any exposure to immune checkpoint inhibitor (ICIs) since the time of first being diagnosed with uveal melanoma.
• Known acute or chronic Hepatitis B or C infection or human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
• Current active significant herpetic infections or prior complications of HSV-1 infection.
• Any central nervous system (CNS) involvement of melanoma, including carcinomatous meningitis.
• Major surgery ≤ 2 weeks prior to the first dose of study intervention.
• Any bleeding, thrombotic and/or other event that places the patient at an unacceptable risk of complications of intratumoral therapy.
• Active, known, or suspected autoimmune disease requiring systemic treatment.
• Prior treatment with an oncolytic virus.
• Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
• Systemic anticancer therapy or prior radiotherapy within 2 weeks of the first dose.
• Has received Investigation agent within 4 weeks or 5 half-lives (whichever longer) prior to the first dose.
• Conditions requiring treatment with immunosuppressive doses (> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.

Additional inclusion/ exclusion criteria are outlined in the study protocol

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 · 29 центров

• HonorHealth Research Insisute — Scottsdale
• UC San Diego Moores Cancer Center — La Jolla
• The Angeles Clinic and Research Institute — Los Angeles
• University of California Los Angeles — Los Angeles
• Stanford Cancer Institute — Palo Alto
• University of Colorado Hospital - Anschutz Cancer Pavilion(ACP) — Aurora
• The Melanoma & Skin Cancer Institute — Englewood
• Georgetown University Medical Center — Washington D.C.
• … и ещё 21 центр

Австралия · 2 центра

• Melanoma Institute Australia — Wollstonecraft
• Peter MacCallum Cancer Centre — Melbourne

Великобритания · 2 центра

• The Clatterbridge Cancer Centre NHS Foundation Trust — Liverpool
• The Royal Marsden NHS Foundation Trust — London

Идентификаторы

NCT: NCT06581406 · RP2-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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