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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. september 2026 opdateret af: 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).

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

350

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Dose Escalation

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

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

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

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

Medicin: Paclitaxel

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

Medicin: Gemcitabine

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

Medicin: Abraxane

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

Medicin: FOLFOX

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

Medicin: FOLFIRINOX

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

Medicin: TAS 102

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

Medicin: Bevacizumab

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

Medicin: NALIRIFOX

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

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

Medicin: FOLFOX

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

Medicin: KEYTRUDA® (pembrolizumab)

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

Medicin: CAPOX

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

Medicin: Gemcitabine Combined With Cisplatin

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

Hvad måler undersøgelsen?

Primære resultatmål

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

Sekundære resultatmål

Resultatmål
Tidsramme
At evaluere farmakokinetikken for spevatamig (PT886).
Tidsramme: Gennem undersøgelsesafslutning, i gennemsnit 2 år
Gennem undersøgelsesafslutning, i gennemsnit 2 år
At evaluere immunogeniciteten (ADA) af spevatamig (PT886).
Tidsramme: Gennem undersøgelsesafslutning, i gennemsnit 2 år
Gennem undersøgelsesafslutning, i gennemsnit 2 år
To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.
Tidsramme: Through study completion, an average of 2 years
Through study completion, an average of 2 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Phanes Therapeutics

Samarbejdspartnere

Merck Sharp & Dohme LLC

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

15. marts 2023

Primær færdiggørelse (Anslået)

1. december 2027

Studieafslutning (Anslået)

1. april 2028

Datoer for studieregistrering

Først indsendt

25. juli 2022

Først indsendt, der opfyldte QC-kriterier

28. juli 2022

Først opslået (Faktiske)

1. august 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

28. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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