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)

Official title

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

Overview

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

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

Primary outcome measures

• To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy. [Time frame: 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. [Time frame: Through study completion.]
• To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy. [Time frame: Through study completion.]

Secondary outcome measures (3)

• To evaluate the pharmacokinetics of Spevatamig (PT886). [Time frame: Through study completion, an average of 2 years]
• To evaluate the immunogenicity (ADA) of Spevatamig (PT886). [Time frame: 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. [Time frame: Through study completion, an average of 2 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• 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
• … and 3 more centers

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗