Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or Targeted Therapy and/or ICI, for the Treatment of Patients With Advanced Gastrointestinal Cancers, Including 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 Followed by a Multi-cohorT Study in Patients With Advanced Gastrointestinal Cancers, Including GastrIc, Gastroesophageal JuNction, Pancreatic Ductal or Biliary Tract AdEnocarcinomas of PT886, in Combination With ChemotherApy, Targeted Therapy, and/or an Immune ChecKpoint Inhibitor. The TWINPEAK Study

Status

Recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05482893

Enrollment

350

Registered

2022-08-01

Start date

2023-03-15

Completion date

2028-04-01

Last updated

2026-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancer (BTC), Colorectal Cancer

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), pancreatic ductal adenocarcinoma (PDAC) and colorectal carcinoma (CRC).

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: substudy C1

DRUGGemcitabine

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

DRUGAbraxane

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

DRUGKEYTRUDA® (pembrolizumab)

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

DRUGFOLFOX

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

DRUGCAPOX

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

DRUGFOLFIRINOX

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

DRUGTAS 102

Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudies C5 and C7.

DRUGBevacizumab

Targeted therapy as a combination partner to Spevatamig (PT886) in Part C: substudies C6 and C7.

DRUGGemcitabine Combined With Cisplatin

Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab) in Part D: substudy D2

DRUGNALIRIFOX

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

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

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: 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 B: Patients with PDAC and GC/GEJC must meet the same criteria as those in Part A depending on which indication and line of treatment are chosen for expansion. Patients considered 2L with BTC, without actionable genomic mutations. Patients considered 3L with CRC. Part C, substudy C1: patients with 2L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with Paclitaxel. Patients who are HER2 positive are eligible. Part C, substudy C2: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, substudy C3: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX or NALIRIFOX. Part C, substudy C4: Patients with m/a BTC without actionable genomic mutations who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment. Part C, substudy C5 and C7: Patients with CRC who are considered 3L, TAS-102 treatment naïve, eligible to receive 3L SOC TAS-102 treatment, and able to swallow oral tablets. Part C, substudy C6 and C7: Patients with CRC who are considered 3L, and eligible to receive bevacizumab treatment, with no contraindication to bevacizumab Part D, substudy D2: patients with m/a BTC with adenocarcinoma histology only, who are treatment naïve for their m/a disease and are eligible for treatment with SOC chemotherapy and ICI. Part D, substudy D3: patients with 2L or 3L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, substudy D4: patients with 1L HER2 negative m/a GC/GEJ-C 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

Design outcomes

Primary

Measure	Time frame
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

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
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

Countries

United States

Contacts

CONTACTPhanes Therapeutics

clinical-trials@phanestx.com858-766-0852

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Sep 29, 2026