A Study of OTP-01, a Dual Paratopic PD-1/VEGFR2 Antibody, in Patients With Advanced Solid Tumors

Официальное название

Phase 1/2A Study of OTP-01, a Dual Paratopic PD-1/VEGFR2 Antibody, in Patients With Advanced Solid Tumors

Обзор

The main goals of this clinical trial are to find out what the best dose of the study drug, OTP-01, is for patients with solid tumors through understanding how it is tolerated and any side effects that it may cause. The trial will also see if OTP-01 causes tumors to shrink and how the body processes OTP-01 by measuring drug levels in the blood. The main questions this study aims to answer are: * What is the recommended dose of OTP-01 for adults with solid tumors? * Is OTP-01 safe and tolerable? * Does OTP-01 reduce tumor growth? Participants will: * Receive OTP-01 through an infusion into a vein. Doses will be spaced out and never more than once a week. * Have blood tests to evaluate safety and drug levels of OTP-01. These will be done often at first and then less frequently as treatment continues. * Have radiographic scans of their tumor at baseline and during the study at regular intervals. * Have the choice to have an optional tumor biopsy before and after treatment to help researchers understand how OTP-01 affects cancer and the immune system. These biopsies are voluntary and will not affect participation in the study.

Вмешательства

• Препарат OTP-01
  Intravenous (IV) Infusion

Первичные конечные точки

• Phase 1 and Phase 2A: Frequency and Severity of adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 2A - Progression Free Survival (PFS) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 2A - Disease Control Rate (DCR) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 2A - Duration of Response (DOR) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 2A - Objective Response Rate (ORR) [Срок оценки: C1D1 through EoT (up to 36 months)]

Вторичные конечные точки (11)

• Phase 1 and Phase 2A - plasma concentrations of OTP-01 [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Area under the curve [AUC] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Maximum plasma concentration [Cmax] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Minimum plasma concentration [Cmin] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Time of maximum concentration [Tmax] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Half-life [t1/2] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 and Phase 2A - Clearance [CL] [Срок оценки: C1D1 through EOT (up to 36 months)]
• Phase 1 - Progression Free Survival (PFS) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 1 - Disease Control Rate (DCR) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 1 - Duration of Response (DOR) [Срок оценки: C1D1 through EoT (up to 36 months)]
• Phase 1 - Objective Response Rate (ORR) [Срок оценки: C1D1 through EoT (up to 36 months)]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed advanced (incurable, recurrent, unresectable, or metastatic) solid tumors.

• For dose escalation cohort patients: patients must have a tumor type as defined in the protocol. Patients will have progression on or after or intolerance to most recent systemic therapy. Patients must have received approved standard therapy that is available to the patient that is known to confer clinical benefit, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. The reason for treatment decline must be clearly documented in the medical record.
• For backfill cohorts: patients must have a tumor type as defined in the protocol. If patients decline an available standard therapeutic regimen known to confer benefit to enroll on this study, the discussion must be clearly documented in the medical record.
• Measurable disease per RECIST v1.1. Additionally, patients with breast or ovarian cancer with non-measurable, evaluable disease are eligible.
• ECOG performance status 0-1.
• Life expectancy of at least 3 months.
• Willing to provide a pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy).
• All toxicity resulting from prior cancer therapies must have resolved to NCI CTCAE v5.0 ≤ Grade 1 or pre-therapy baseline with the exception of alopecia or ≤ Grade 2 neuropathy.
• Adequate hematological, renal, and hepatic function.
• Other protocol-defined inclusion criteria apply.

Критерии исключения

• Receiving systemic corticosteroids at prednisone-equivalent dose of > 10 mg/day within 4 weeks prior to signing consent. Chronic systemic corticosteroid therapy for physiologic replacement (≤ 10 mg/day of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted
• History of Grade 4 allergic or anaphylactic reaction to prior monoclonal antibody therapy or allergic reaction to any excipients within the investigational product
• History of toxicity requiring permanent discontinuation of prior cancer immunotherapy
• Have an active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment)
• History of organ or stem cell transplant or need for immunosuppressive treatment
• Have proteinuria > 2 + (within 7 days prior to initiation of study treatment).
• Received any chemotherapy, immunotherapy or investigational anticancer therapy within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug
• Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug. If previously irradiated, lesions must have demonstrated clear-cut progression prior to being eligible for evaluation as target lesions
• Other protocol and subprotocol-defined exclusion criteria apply

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

Другое

Центры проведения

США · 5 центров

• Yale Cancer Center — New Haven
• Dana-Farber Cancer Institute — Boston
• South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids
• South Texas Accelerated Research Therapeutics (START) — San Antonio
• START Mountain Region — West Valley City

Австралия · 3 центра

• Cancer Research SA — Adelaide
• Chris O'Brien Lifehouse — Camperdown
• Linear Clinical Research — Nedlands

Ирландия · 1 центр

• START Dublin Early Phase Clinical Trials Unit — Dublin

Новая Зеландия · 1 центр

• Auckland City Hospital — Auckland

Португалия · 1 центр

• Hospital de Santa-Maria-Centro Hospitalar Lisboa Norte (CHLN) — Lisbon

Испания · 1 центр

• Fundación Jiménez Díaz — Madrid

Идентификаторы

NCT: NCT07266428 · OTP-01-101 · 2025-524111-37-00 · U1111-1329-6711

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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