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)
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
2 other identifiers
interventional
258
1 country
11
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2023
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2022
CompletedFirst Posted
Study publicly available on registry
August 1, 2022
CompletedStudy Start
First participant enrolled
March 15, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2028
July 9, 2026
July 1, 2026
4.7 years
July 25, 2022
July 7, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
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.
Through study completion.
To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.
Through study completion.
Secondary Outcomes (3)
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
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
Study Arms (4)
Dose Escalation
EXPERIMENTALAn accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels.
Dose Expansion
EXPERIMENTALTwo dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level.
Combination Expansion with Chemotherapy
EXPERIMENTALPart 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.
Combination Expansion with KEYTRUDA® (pembrolizumab)
EXPERIMENTALPart 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).
Interventions
Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.
Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C1
Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: substudy C2
Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: substudy C2
Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D.
Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3
Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only)
Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886)
Eligibility Criteria
You may qualify if:
- 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.
- \. 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLCcollaborator
- Phanes Therapeuticslead
Study Sites (11)
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Sarah Cannon Research Institute (SCRI)
Denver, Colorado, 80218, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215, United States
Duke Cancer Center
Durham, North Carolina, 27710, United States
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15232, United States
MD Anderson Cancer Center, GI Medical Oncology Dept
Houston, Texas, 77030, United States
NEXT Oncology
Fairfax, Virginia, 22031, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2022
First Posted
August 1, 2022
Study Start
March 15, 2023
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
April 1, 2028
Last Updated
July 9, 2026
Record last verified: 2026-07