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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)

23 septembre 2026 mis à jour par: Phanes Therapeutics

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

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).

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

350

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • États-Unis
    • California
      • Duarte, California, États-Unis, 91010
        • Recrutement
        • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
      • Los Angeles, California, États-Unis, 90033
        • Recrutement
        • USC Norris Comprehensive Cancer Center
    • Colorado
      • Denver, Colorado, États-Unis, 80218
        • Recrutement
        • Sarah Cannon Research Institute (SCRI)
    • Iowa
      • Iowa City, Iowa, États-Unis, 52242
        • Recrutement
        • University of Iowa
    • Kentucky
      • Louisville, Kentucky, États-Unis, 40202
        • Recrutement
        • Norton Cancer Institute
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02215
        • Actif, ne recrute pas
        • Dana-Farber Cancer Institute (DFCI)
    • North Carolina
      • Durham, North Carolina, États-Unis, 27710
        • Recrutement
        • Duke Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, États-Unis, 15232
        • Recrutement
        • University of Pittsburgh Medical Center (UPMC)
    • Texas
      • Houston, Texas, États-Unis, 77030
        • Recrutement
        • MD Anderson Cancer Center, GI Medical Oncology Dept
    • Virginia
      • Fairfax, Virginia, États-Unis, 22031
        • Recrutement
        • NEXT Oncology
    • Wisconsin
      • Madison, Wisconsin, États-Unis, 53792
        • Recrutement
        • University of Wisconsin Carbone Cancer Center - University Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 exclusion criteria will apply.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Dose Escalation

An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels.
Médicament: Spevatamig (PT886)

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

One or more indications (GC/GEJC, BTC, CRC or PDAC) and/or lines of treatment may be selected for dose expansion at two dose levels (RDE1 and RDE2).
Médicament: Spevatamig (PT886)

Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.
Expérimental: Combination Expansion with Chemotherapy or Targeted Therapy

Part C, substudy C1: patients with 2L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with Paclitaxel.

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 2L BTC will receive PT886 in combination with SOC chemotherapy mFOLFOX6.

Part C, substudy C5: patients with 3L CRC patients will receive PT886 in combination with SOC chemotherapy TAS-102.

Part C, substudy C6: patients with 3L CRC patients will receive PT886 in combination with bevacizumab.

Part C, substudy C7: patients with 3L CRC patients will receive PT886 in combination with SOC chemotherapy TAS-102 and bevacizumab.
Médicament: Spevatamig (PT886)

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

Médicament: Paclitaxel

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

Médicament: Gemcitabine

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

Médicament: Abraxane

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

Médicament: FOLFOX

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

Médicament: FOLFIRINOX

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

Médicament: TAS 102

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

Médicament: Bevacizumab

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

Médicament: NALIRIFOX

Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3.
Expérimental: Combination Expansion with KEYTRUDA® (pembrolizumab)

Part D, substudy D2: patients with 1L BTC will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab) and standard of care chemotherapy GemCis.

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).
Médicament: Spevatamig (PT886)

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

Médicament: FOLFOX

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

Médicament: KEYTRUDA® (pembrolizumab)

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

Médicament: CAPOX

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

Médicament: Gemcitabine Combined With Cisplatin

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

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
Délai: Through study completion, an average of 2 years
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.
Délai: Through study completion.
Through study completion.
To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.
Délai: Through study completion.
Through study completion.

Mesures de résultats secondaires

Mesure des résultats
Délai
Pour évaluer la pharmacocinétique de Spevatamig (PT886).
Délai: Grâce à l'achèvement de l'étude, une moyenne de 2 ans
Grâce à l'achèvement de l'étude, une moyenne de 2 ans
Évaluer l'immunogénicité (ADA) de Spevatamig (PT886).
Délai: Grâce à l'achèvement de l'étude, une moyenne de 2 ans
Grâce à l'achèvement de l'étude, une moyenne de 2 ans
To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.
Délai: Through study completion, an average of 2 years
Through study completion, an average of 2 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Phanes Therapeutics

Collaborateurs

Merck Sharp & Dohme LLC

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

15 mars 2023

Achèvement primaire (Estimé)

1 décembre 2027

Achèvement de l'étude (Estimé)

1 avril 2028

Dates d'inscription aux études

Première soumission

25 juillet 2022

Première soumission répondant aux critères de contrôle qualité

28 juillet 2022

Première publication (Réel)

1 août 2022

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

28 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

23 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • PT886X1101
  • KEYNOTE-F58 (MK-3475-F58) (Autre identifiant: Merck Sharp & Dohme, LLC)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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