A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors

Официальное название

A Phase 1a/1b Multicenter, Open-label Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of PLN-101095 as Monotherapy and in Combination With Pembrolizumab in Adult Participants With Advanced or Metastatic Solid Tumors Who Have Disease Progression While on an Immune Checkpoint Inhibitor (FORTIFY)

Обзор

This is a Phase 1a/1b, dose-escalation/expansion, consecutive-cohort, open-label study to evaluate the safety, tolerability, PK, PD, and preliminary evidence of antitumor activity of PLN-101095 in combination with pembrolizumab (the study treatment regimen) in adult participants with advanced or metastatic solid tumors for which pembrolizumab is indicated but have documented disease progression (refractory \[primary resistance\]) or relapsed \[secondary resistance\]) after at least 3 months from the start of treatment with pembrolizumab. The study will consist of 2 main parts: * Part 1: Consecutive dose-escalation cohorts using a Bayesian optimal interval (BOIN) dose escalation design with accelerated titration * Part 2: Dose-expansion cohorts using Simon's 2-stage design

Вмешательства

• Препарат PLN-101095
  PLN-101095 250 mg BID
• Препарат PLN-101095
  PLN-101095 500 mg BID
• Препарат PLN-101095
  PLN-101095 1000 mg BID
• Препарат PLN-101095
  PLN-101095 1000 mg TID
• Препарат PLN-101095
  PLN-101095 2000 mg BID
• Препарат PLN-101095
  PLN-101095
• Препарат Pembrolizumab
  Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

Первичные конечные точки

• Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 [Срок оценки: First dose to 35 days]
• Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 [Срок оценки: Day 1 until 16 weeks after end of study treatment regimen]
• Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 [Срок оценки: First dose to disease progression or death from any cause, whichever occurs first.]
• Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 [Срок оценки: First dose to disease progression or death from any cause, whichever occurs first.]

Вторичные конечные точки (5)

• PK of PLN-101095 monotherapy in Parts 1 and 2 [Срок оценки: Day 14, 0 to up to 12 hours]
• PK of PLN-101095 monotherapy in Parts 1 and 2 [Срок оценки: Day 14, 0 to up to 12 hours]
• PK of PLN-101095 monotherapy in Parts 1 and 2 [Срок оценки: Day 14, 0 to up to 12 hours]
• Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 [Срок оценки: First objective response (CR or PR) to disease progression or death from any cause, whichever occurs first]
• Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 [Срок оценки: First dose to progression or death from any cause, whichever occurs first]

Критерии участия

Критерии включения

• Has histologically or cytologically confirmed advanced or metastatic solid tumor
• Have received ≥12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment administered as monotherapy or in combination with other anticancer therapies
• Have demonstrated documented prior clinical benefit, defined as CR or PR at any time during treatment, or SD lasting ≥6 months (Part 2 only)
• Must have subsequently developed radiographic disease progression while receiving anti-PD-1 or anti-PD-L1 treatment or within ≤12 weeks after the last dose of such treatment
• At least 1 measurable lesion, as defined by RECIST v1.1
• Estimated survival of ≥3 months
• Have adequate bone marrow and organ function.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding

Критерии исключения

• Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has received prior radiotherapy within 2 weeks for palliative bone-directed therapy and 4 weeks for all other radiotherapy
• Has undergone major surgery within 4 weeks prior to the first dose of study treatment or has not adequately recovered from surgery or related complications
• Has a diagnosis of immunodeficiency or use of systemic steroids >10 mg/day
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has known active CNS metastases (brain and/or leptomeningeal metastases)
• Has significant cardiac disease
• Has an active infection requiring systemic therapy (including uncontrolled HIV, Hepatitis B and C)
• Has received a live or live-attenuated vaccine within 30 days or a non-live vaccine within 7 days prior to the first dose of PLN-101095

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

США · 12 центров

• Yale University — New Haven
• Winship Cancer Institute of Emory University — Atlanta
• South Texas Accelerated Research Therapeutics (START) — Grand Rapids
• START New Jersey — East Brunswick
• START New York Long Island LLC — Lake Success
• Carolina Cancer Research Center — Wilson
• NEXT Austin — Austin
• START Center for Clinical Research — Fort Worth
• … и ещё 4 центра

Идентификаторы

NCT: NCT06270706 · PLN-101095-ONC-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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