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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 258
- 试验地点
- 21
- 主要终点
- To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Adequate organ function confirmed at screening and within 72 hours of initiating treatment.
排除标准
- •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.
研究组 & 干预措施
Dose Escalation
An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels.
干预措施: Spevatamig (PT886) (Drug)
Dose Expansion
Two dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level.
干预措施: Spevatamig (PT886) (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: Spevatamig (PT886) (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: FOLFIRINOX (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: Paclitaxel (Drug)
Combination Expansion with KEYTRUDA® (pembrolizumab)
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).
干预措施: KEYTRUDA® (pembrolizumab) (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: Gemcitabine (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: Abraxane (Drug)
Combination Expansion with KEYTRUDA® (pembrolizumab)
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).
干预措施: Spevatamig (PT886) (Drug)
Combination Expansion with Chemotherapy
Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.
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: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.
干预措施: FOLFOX (Drug)
Combination Expansion with KEYTRUDA® (pembrolizumab)
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).
干预措施: FOLFOX (Drug)
Combination Expansion with KEYTRUDA® (pembrolizumab)
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).
干预措施: CAPOX (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
时间窗: 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.
时间窗: Through study completion.
To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.
时间窗: Through study completion.
次要结局
- To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.(Through study completion, an average of 2 years)
- To evaluate the pharmacokinetics of Spevatamig (PT886).(Through study completion, an average of 2 years)
- To evaluate the immunogenicity (ADA) of Spevatamig (PT886).(Through study completion, an average of 2 years)