Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junction, Pancreatic Ductal or Biliary Tract Carcinomas (the TWINPEAK Study)

Официальное название

A Phase 1/2, Open-Label, Dose Escalation and Expansion Study With PT886 (Spevatamig) Followed by a Multi-cohorT Study in Patients With Advanced GastrIc, Gastroesophageal JuNction, Pancreatic Ductal or Biliary Tract AdEnocarcinomas of PT886, in Combination With ChemotherApy, and/or an Immune ChecKpoint Inhibitor. The TWINPEAK Study

Обзор

This is a first-in-human, Phase 1/2, open-label, dose escalation and dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Spevatamig (PT886). Patients with the following tumor types will be eligible for screening: unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, biliary tract carcinoma (BTC) and pancreatic ductal adenocarcinoma (PDAC).

Вмешательства

• Препарат Spevatamig (PT886)
  Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.
• Препарат Paclitaxel
  Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C1
• Препарат Gemcitabine
  Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: substudy C2
• Препарат Abraxane
  Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: substudy C2
• Препарат KEYTRUDA® (pembrolizumab)
  Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D.
• Препарат FOLFOX
  Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only)
• Препарат CAPOX
  Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886)
• Препарат FOLFIRINOX
  Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3

Первичные конечные точки

• To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy. [Срок оценки: Through study completion, an average of 2 years]
• To evaluate anti-tumor activity of PT886 as assessed by ORR, in Spevatamig (PT886) monotherapy and in each combination substudy. [Срок оценки: Through study completion.]
• To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy. [Срок оценки: Through study completion.]

Вторичные конечные точки (3)

• To evaluate the pharmacokinetics of Spevatamig (PT886). [Срок оценки: Through study completion, an average of 2 years]
• To evaluate the immunogenicity (ADA) of Spevatamig (PT886). [Срок оценки: Through study completion, an average of 2 years]
• To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy. [Срок оценки: Through study completion, an average of 2 years]

Критерии участия

Критерии включения

• 18 years or older and able to sign informed consent and comply with the protocol.
• Measurable disease as defined by RECIST V1.1 criteria for solid tumors.
• 3\. Part A and Part B: Histologically or cytologically confirmed unresectable advanced or metastatic solid gastric, gastroesophageal junction (GEJ), biliary tract or pancreatic carcinomas previously treated for advanced (metastatic or unresectable) disease or for which treatment is not available or not tolerated.

Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Patients who are HER2 positive are eligible.

Part C, substudy C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane).

Part C, substudy C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX.

Part C, substudy C4: Patients with m/a BTC who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment.

Part D, substudy D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).

Part D, substudy D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).

• Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably fresh biopsy or if not possible, archival tissue) to be assessed for CLDN18.2 expression and other biomarkers.
• ECOG performance status of 0 or 1.
• Adequate organ function confirmed at screening and within 72 hours of initiating treatment.

Критерии исключения

Patients are excluded from the study if any of the following criteria apply:

• Women who are pregnant or lactating.
• Women of child-bearing potential (WOCBP) who do not use adequate birth control.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents.

Additional inclusion and exclusion criteria will 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

Лечение

Центры проведения

США · 11 центров

• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• USC Norris Comprehensive Cancer Center — Los Angeles
• Sarah Cannon Research Institute (SCRI) — Denver
• University of Iowa — Iowa City
• Norton Cancer Institute — Louisville
• Dana-Farber Cancer Institute (DFCI) — Boston
• Duke Cancer Center — Durham
• University of Pittsburgh Medical Center (UPMC) — Pittsburgh
• … и ещё 3 центра

Идентификаторы

NCT: NCT05482893 · PT886X1101 · KEYNOTE-F58 (MK-3475-F58)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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