Gastric or Gastroesophageal Junction Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancer (BTC)
Conditions
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).
Interventions
DRUGSpevatamig (PT886)
Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.
DRUGPaclitaxel
Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: Cohort C1
DRUGGemcitabine
Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: Cohort C2
DRUGAbraxane
Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: Cohort C2
Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D: Cohort D2, D3 and D4.
DRUGOxaliplatin
Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4
DRUGLeucovorin
Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4
DRUGFluorouracil
Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4
DRUGCapecitabine
Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4
DRUGFOLFIRINOX
Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: Cohort C3
Sponsors
Merck Sharp & Dohme LLC
Phanes Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. 18 years or older and able to sign informed consent and comply with the protocol. 2. Measurable disease as defined by RECIST V1.1 criteria for solid tumors. 3. 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, Cohort 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, 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. Cohort C4: Patients with m/a BTC who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment. Cohort C5: Patients with m/a HER2 negative GC/GEJC and present a PD-L1 CPS score of \<1%, who are treatment naïve for their m/a disease and eligible for treatment with SOC chemotherapy (mFOLFOX6 or CAPOX). 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). 4. Biopsies: 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. Parts C and D: Patients must present with ≥ 10%; ≥ 2+ CLDN18.2 positive TC in their tumor tissue. 5. ECOG performance status of 0 or 1. 6. Adequate organ function confirmed at screening and within 72 hours of initiating treatment. Key
Exclusion criteria
Patients are excluded from the study if any of the following criteria apply: 1. Women who are pregnant or lactating. 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control. 3. Has an active autoimmune disease that has required systemic treatment in the past 2 years. 4. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to study treatment. 5. Patients with a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or have a history of interstitial lung disease. History of COVID-19 pneumonia with fibrotic changes. 6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases). 7. Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents. For Part D, Cohort D2, prior treatment with zolbetuximab is allowed. 8. Impaired cardiac function or significant diseases. 9. Prior hemolytic anemia or Evans Syndrome in the last 3 months. 10. Active gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention. 11. Patients who have experienced any thromboembolic event such as deep vein thrombosis (DVT) or pulmonary embolism in the past 6 months. Additional inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactPhanes Therapeutics
Outcome results
None listed