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
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).
Panoramica dello studio
Stato
Condizioni
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: Phanes Therapeutics
- Numero di telefono: 858-766-0852
- Email: clinical-trials@phanestx.com
Luoghi di studio
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California
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Duarte, California, Stati Uniti, 91010
- Reclutamento
- City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
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Los Angeles, California, Stati Uniti, 90033
- Reclutamento
- USC Norris Comprehensive Cancer Center
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Colorado
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Denver, Colorado, Stati Uniti, 80218
- Reclutamento
- Sarah Cannon Research Institute (SCRI)
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Iowa
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Iowa City, Iowa, Stati Uniti, 52242
- Reclutamento
- University of Iowa
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Kentucky
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Louisville, Kentucky, Stati Uniti, 40202
- Reclutamento
- Norton Cancer Institute
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Attivo, non reclutante
- Dana-Farber Cancer Institute (DFCI)
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North Carolina
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Durham, North Carolina, Stati Uniti, 27710
- Reclutamento
- Duke Cancer Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Stati Uniti, 15232
- Reclutamento
- University of Pittsburgh Medical Center (UPMC)
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Texas
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Houston, Texas, Stati Uniti, 77030
- Reclutamento
- MD Anderson Cancer Center, GI Medical Oncology Dept
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Virginia
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Fairfax, Virginia, Stati Uniti, 22031
- Reclutamento
- NEXT Oncology
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Wisconsin
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Madison, Wisconsin, Stati Uniti, 53792
- Reclutamento
- University of Wisconsin Carbone Cancer Center - University Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Key Inclusion Criteria
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18 years or older and able to sign informed consent and comply with the protocol.
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Measurable disease as defined by RECIST V1.1 criteria for solid tumors.
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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).
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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.
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ECOG performance status of 0 or 1.
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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:
- 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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Dose Escalation
An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels. |
Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47. |
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Sperimentale: 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). |
Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47. |
|
Sperimentale: 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. |
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 Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only) Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3 Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudies C5 and C7. Targeted therapy as a combination partner to Spevatamig (PT886) in Part C: substudies C6 and C7. Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3. |
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Sperimentale: 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). |
Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47. Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only) Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D. Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab) in Part D: substudy D2 |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
Lasso di tempo: Through study completion, an average of 2 years
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Through study completion, an average of 2 years
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To evaluate anti-tumor activity of PT886 as assessed by ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.
Lasso di tempo: Through study completion.
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Through study completion.
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To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.
Lasso di tempo: Through study completion.
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Through study completion.
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Per valutare la farmacocinetica di spevatamig (PT886).
Lasso di tempo: Attraverso il completamento dello studio, una media di 2 anni
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Attraverso il completamento dello studio, una media di 2 anni
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Per valutare l'immunogenicità (ADA) di Spevatamig (PT886).
Lasso di tempo: Attraverso il completamento dello studio, una media di 2 anni
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Attraverso il completamento dello studio, una media di 2 anni
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To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.
Lasso di tempo: Through study completion, an average of 2 years
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Through study completion, an average of 2 years
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Collaboratori e investigatori
Sponsor
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Neoplasie per sede
- Neoplasie
- Malattie intestinali
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie dell'apparato digerente
- Malattie gastrointestinali
- Neoplasie intestinali
- Malattie del retto
- Malattie delle vie biliari
- Malattie del colon
- Neoplasie delle vie biliari
- Neoplasie colorettali
- Aminoacidi, peptidi e proteine
- Proteine
- Prodotti chimici organici
- Composti eterociclici, 1-anello
- Composti eterociclici
- Idrocarburi
- Cicloparaffins
- Idrocarburi, aliciclici
- Idrocarburi, ciclici
- Terpeni
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Prodotti chimici inorganici
- Composti di cloro
- Composti di azoto
- Taxoidi
- Ciclodecani
- Diterpenes
- Deossictidina
- Citidina
- Nucleosidi di pirimidina
- Pirimidine
- Composti di platino
- Albumine
- Bevacizumab
- Paclitaxel legato all'albumina
- Gemcitabina
- Paclitaxel
- Cisplatino
- combinazione di droghe di trifluridina tipiracile
- pembrolizumab
- Protocollo Folfox
- folfirinox
Altri numeri di identificazione dello studio
- PT886X1101
- KEYNOTE-F58 (MK-3475-F58) (Altro identificatore: Merck Sharp & Dohme, LLC)
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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