Étude sur l'augmentation et l'expansion de la dose du HM16390 dans les tumeurs solides avancées ou métastatiques
Une étude de phase I, ouverte, multicentrique, d'augmentation et d'expansion de la dose du HM16390 chez des patients atteints de tumeurs solides avancées ou métastatiques
This is a First-in-Human, Phase 1, Dose-Escalation and Dose-Expansion study of HM16390, as a single agent and in combination with pembrolizumab to assess safety, tolerability, MTD, RP2D, PK, and efficacy in patients with advanced or metastatic solid tumors.
Dose-Escalation Part is planned to establish the MTD or RDs for the randomized Dose-Ranging Part. Based on the results of the Dose-Escalation Part, additional eligible subjects will be randomized 1:1 into each dose level. After a comprehensive review of available data from both Dose-Escalation Part and Dose-Ranging Part, the RDEs to be tested in the Dose-Expansion Part are determined. Dose-Expansion Part is designed to assess the potential efficacy of HM16390 as a single agent and in combination with pembrolizumab when administered at the RDEs to subjects in indication-specific expansion cohorts.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Hyebin Son
- Numéro de téléphone: 82-2-410-9835
- E-mail: hyebin.son@hanmi.co.kr
Lieux d'étude
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Seoul, Corée du Sud, 03080
- Recrutement
- Seoul National University Hospital
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Seoul, Corée du Sud, 06351
- Recrutement
- Samsung Medical Center
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Seoul, Corée du Sud, 03722
- Recrutement
- Severance Hospital
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Seoul, Corée du Sud, 05505
- Actif, ne recrute pas
- Asan Medical Center
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Gyeonggi-do
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Seongnam-si, Gyeonggi-do, Corée du Sud, 13620
- Recrutement
- Seoul National University Bundang Hospital
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California
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Los Angeles, California, États-Unis, 90095
- Recrutement
- The Regents of the University of California on behalf of its Los Angeles campus
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Massachusetts
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Boston, Massachusetts, États-Unis, 02114
- Recrutement
- Massachusetts General Hospital
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Michigan
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Detroit, Michigan, États-Unis, 48201
- Recrutement
- Karmanos Cancer Institute
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Key Inclusion Criteria:
- Have a histologically and/or cytologically confirmed advanced or metastatic solid tumor and have failed or are intolerant to standard therapy with clinical benefit.
- Patients in the Dose-Escalation Part must have evaluable or measurable disease at baseline and the patients for Dose-Ranging and Dose-Expansion Part must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before allocation or randomization.
- Age of 18 years or older (or country's legal age of majority if the legal age was >18 years)
- Adequate renal function.
- Adequate hematologic function.
- Adequate liver function.
Key Exclusion Criteria:
- Received prior treatment with agent targeting the IL-2, IL-7, or IL-15 receptors, or related to mode of action of HM16390.
- Known active CNS metastases and/or carcinomatous meningitis.
- History of severe toxicities associated with a prior immunotherapy.
- Any prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) clinically significant toxicities that have not resolved to Grade ≤ 1 per NCI-CTCAE version 5.0 or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrollment.
- Has ongoing or suspected autoimmune disease.
- Known active and clinically significant bacterial, fungal or viral infection including known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, immunocompromised patients.
- History of chronic liver disease or evidence of hepatic cirrhosis.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: HM16390
HM16390 Monotherapy |
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
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Expérimental: HM16390 + pembrolizumab
HM16390 in combination with pembrolizumab |
Fixed dose of pembrolizumab will be administered as an IV infusion over 30 minutes on Day 1 of every 3-week treatment cycle
Autres noms:
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence and nature of DLTs
Délai: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
|
To evaluate safety and tolerability of HM16390 as a single agent and in combination with pembrolizumab |
At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
|
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Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
Délai: Throughout the study until end of safety follow-up period (90 days after the last treatment)
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To evaluate safety and tolerability of HM16390 as a single agent, and in combination with pembrolizumab |
Throughout the study until end of safety follow-up period (90 days after the last treatment)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Objective response rate (ORR)
Délai: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
|
Disease Control Rate (DCR)
Délai: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
DCR will be measured as the proportion of subject with confirmed CR, PR, or Stable Disease (SD) as per RECIST v1.1 |
Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
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The maximum serum concentration (Cmax)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The time to reach Cmax (Tmax)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The area under the concentration-time curve from time 0 to the last observable concentration (AUClast)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The AUC extrapolated to infinity (AUCinf)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
|
The AUC during the dosing interval (AUCtau)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The serum concentration at the end of the dosing interval (Ctrough)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The elimination half-life (T1/2)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
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To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
|
The apparent volume of distribution (Vd/F)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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The apparent clearance (CL/F)
Délai: Throughout the study until treatment discontinuation (up to 2-3 years)
|
To evaluate PK profile upon HM16390 administration |
Throughout the study until treatment discontinuation (up to 2-3 years)
|
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Progression-free survival (PFS)
Délai: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v1.1 or until death from any cause, whichever occurs first |
Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
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Duration of response (DOR)
Délai: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v1.1 or death from any cause, whichever occurs first. |
Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- HM-LIL2-101
- KEYNOTE-G39 (Autre identifiant: Merck & Sharp Dohme LLC)
- MK-3475-G39 (Autre identifiant: Merck & Sharp Dohme LLC)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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