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)

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

• Spevatamig (PT886) · DRUG

  Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.

• Paclitaxel · DRUG

  Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C1

• Gemcitabine · DRUG

  Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: substudy C2

• Abraxane · DRUG

  Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: substudy C2

• KEYTRUDA® (pembrolizumab) · DRUG

  Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D.

• FOLFOX · DRUG

  Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only)

• CAPOX · DRUG

  Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886)

• FOLFIRINOX · DRUG

  Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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, 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).
4. 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.
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. Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents.

Additional inclusion and exclusion criteria will apply.

Sites (11)

• City of Hope (City of Hope National Medical Center, City of Hope Medical Center), Duarte, California · RECRUITING
• USC Norris Comprehensive Cancer Center, Los Angeles, California · RECRUITING
• Sarah Cannon Research Institute (SCRI), Denver, Colorado · RECRUITING
• University of Iowa, Iowa City, Iowa · RECRUITING
• Norton Cancer Institute, Louisville, Kentucky · RECRUITING
• Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts · ACTIVE_NOT_RECRUITING
• Duke Cancer Center, Durham, North Carolina · RECRUITING
• University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania · RECRUITING
• MD Anderson Cancer Center, GI Medical Oncology Dept, Houston, Texas · RECRUITING
• NEXT Oncology, Fairfax, Virginia · RECRUITING
• University of Wisconsin Carbone Cancer Center - University Hospital, Madison, Wisconsin · RECRUITING