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).
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
- Arzneimittel: Spevatamig (PT886)
- Arzneimittel: Paclitaxel
- Arzneimittel: Gemcitabine
- Arzneimittel: Abraxane
- Arzneimittel: FOLFOX
- Arzneimittel: FOLFIRINOX
- Arzneimittel: TAS 102
- Arzneimittel: Bevacizumab
- Arzneimittel: NALIRIFOX
- Arzneimittel: KEYTRUDA® (pembrolizumab)
- Arzneimittel: CAPOX
- Arzneimittel: Gemcitabine Combined With Cisplatin
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: Phanes Therapeutics
- Telefonnummer: 858-766-0852
- E-Mail: clinical-trials@phanestx.com
Studienorte
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California
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Duarte, California, Vereinigte Staaten, 91010
- Rekrutierung
- City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
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Los Angeles, California, Vereinigte Staaten, 90033
- Rekrutierung
- USC Norris Comprehensive Cancer Center
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Colorado
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Denver, Colorado, Vereinigte Staaten, 80218
- Rekrutierung
- Sarah Cannon Research Institute (SCRI)
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Iowa
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Iowa City, Iowa, Vereinigte Staaten, 52242
- Rekrutierung
- University of Iowa
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Kentucky
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Louisville, Kentucky, Vereinigte Staaten, 40202
- Rekrutierung
- Norton Cancer Institute
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02215
- Aktiv, nicht rekrutierend
- Dana-Farber Cancer Institute (DFCI)
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North Carolina
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Durham, North Carolina, Vereinigte Staaten, 27710
- Rekrutierung
- Duke Cancer Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Vereinigte Staaten, 15232
- Rekrutierung
- University of Pittsburgh Medical Center (UPMC)
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Texas
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Houston, Texas, Vereinigte Staaten, 77030
- Rekrutierung
- MD Anderson Cancer Center, GI Medical Oncology Dept
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Virginia
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Fairfax, Virginia, Vereinigte Staaten, 22031
- Rekrutierung
- NEXT Oncology
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Wisconsin
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Madison, Wisconsin, Vereinigte Staaten, 53792
- Rekrutierung
- University of Wisconsin Carbone Cancer Center - University Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: 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. |
|
Experimental: 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. |
|
Experimental: 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. |
|
Experimental: 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 |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.
Zeitfenster: 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.
Zeitfenster: 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.
Zeitfenster: Through study completion.
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Through study completion.
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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Bewertung der Pharmakokinetik von Spevatamig (PT886).
Zeitfenster: Durch Abschluss der Studie durchschnittlich 2 Jahre
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Durch Abschluss der Studie durchschnittlich 2 Jahre
|
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Bewertung der Immunogenität (ADA) von Spevatamig (PT886).
Zeitfenster: Durch Abschluss der Studie durchschnittlich 2 Jahre
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Durch Abschluss der Studie durchschnittlich 2 Jahre
|
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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.
Zeitfenster: Through study completion, an average of 2 years
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Through study completion, an average of 2 years
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Neubildungen nach Standort
- Neubildungen
- Darmerkrankungen
- Gastrointestinale Neubildungen
- Neoplasmen des Verdauungssystems
- Erkrankungen des Verdauungssystems
- Magen-Darm-Erkrankungen
- Darmtumoren
- Rektale Erkrankungen
- Erkrankungen der Gallenwege
- Darmerkrankungen
- Neoplasien der Gallenwege
- Kolorektale Neubildungen
- Aminosäuren, Peptide und Proteine
- Proteine
- Organische Chemikalien
- Heterocyclische Verbindungen, 1-Ring
- Heterocyclische Verbindungen
- Kohlenwasserstoffe
- Cycloparaffine
- Kohlenwasserstoffe, alicyclisch
- Kohlenwasserstoffe, zyklisch
- Terpene
- Antikörper, monoklonal, humanisiert
- Antikörper, monoklonal
- Antikörper
- Immunglobuline
- Immunoproteine
- Blutproteine
- Serumglobuline
- Globuline
- Anorganische Chemikalien
- Chlorverbindungen
- Stickstoffverbindungen
- Taxoid
- Cyclodececane
- Diterpene
- Desoxycytidin
- Cytidin
- Pyrimidin -Nucleoside
- Pyrimidine
- Platinverbindungen
- Albumine
- Bevacizumab
- Albumingebundenes Paclitaxel
- Gemcitabin
- Paclitaxel
- Cisplatin
- Trifluridin -Tipiracil -Arzneimittelkombination
- Pembrolizumab
- FOLFOX -Protokoll
- FOLFIRINOX
Andere Studien-ID-Nummern
- PT886X1101
- KEYNOTE-F58 (MK-3475-F58) (Andere Kennung: Merck Sharp & Dohme, LLC)
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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