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)
Phase 1
Recruiting
- Conditions
- Gastric or Gastroesophageal Junction AdenocarcinomaPancreatic Ductal AdenocarcinomaBiliary Tract Cancer (BTC)
- Interventions
- Registration Number
- NCT05482893
- Lead Sponsor
- Phanes Therapeutics
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 258
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination Expansion with Chemotherapy Abraxane Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Oxaliplatin Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Leucovorin Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Fluorouracil Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Capecitabine Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy FOLFIRINOX Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with KEYTRUDA® (pembrolizumab) Leucovorin Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Combination Expansion with KEYTRUDA® (pembrolizumab) Spevatamig (PT886) Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Combination Expansion with KEYTRUDA® (pembrolizumab) KEYTRUDA® (pembrolizumab) Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Combination Expansion with KEYTRUDA® (pembrolizumab) Oxaliplatin Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Combination Expansion with KEYTRUDA® (pembrolizumab) Fluorouracil Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Combination Expansion with KEYTRUDA® (pembrolizumab) Capecitabine Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab). Dose Escalation Spevatamig (PT886) An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels. Dose Expansion Spevatamig (PT886) Two dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level. Combination Expansion with Chemotherapy Spevatamig (PT886) Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Paclitaxel Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX. Combination Expansion with Chemotherapy Gemcitabine Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX.
- Primary Outcome Measures
Name Time Method To determine the dose-limiting toxicity (DLT) of Spevatamig (PT886). Through study completion. To determine the maximum tolerated dose (MTD) of Spevatamig (PT886). Through study completion. To evaluate the safety and tolerability of Spevatamig (PT886). Through study completion, an average of 2 years
- Secondary Outcome Measures
Name Time Method 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 Preliminary Efficacy of Spevatamig (PT886). Through study completion.
Trial Locations
- Locations (6)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sarah Cannon Research Institute (SCRI)
🇺🇸Denver, Colorado, United States
Dana-Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center, GI Medical Oncology Dept
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸Fairfax, Virginia, United States