Studie eskalace a expanze dávky HM16390 u pokročilých nebo metastatických pevných nádorů
Fáze I, otevřená, multicentrická studie eskalace a expanze dávky HM16390 u pacientů s pokročilými nebo metastatickými solidními nádory
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.
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Hyebin Son
- Telefonní číslo: 82-2-410-9835
- E-mail: hyebin.son@hanmi.co.kr
Studijní místa
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Seoul, Jižní Korea, 03080
- Nábor
- Seoul National University Hospital
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Seoul, Jižní Korea, 06351
- Nábor
- Samsung Medical Center
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Seoul, Jižní Korea, 03722
- Nábor
- Severance Hospital
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Seoul, Jižní Korea, 05505
- Aktivní, ne nábor
- Asan Medical Center
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Gyeonggi-do
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Seongnam-si, Gyeonggi-do, Jižní Korea, 13620
- Nábor
- Seoul National University Bundang Hospital
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California
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Los Angeles, California, Spojené státy, 90095
- Nábor
- 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, Spojené státy, 02114
- Nábor
- Massachusetts General Hospital
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Michigan
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Detroit, Michigan, Spojené státy, 48201
- Nábor
- Karmanos Cancer Institute
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: HM16390
HM16390 Monotherapy |
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
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Experimentální: 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
Ostatní jména:
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Incidence and nature of DLTs
Časové okno: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
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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.
Časové okno: Throughout the study until end of safety follow-up period (90 days after the last treatment)
|
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)
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Objective response rate (ORR)
Časové okno: 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)
|
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Disease Control Rate (DCR)
Časové okno: 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)
Časové okno: 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)
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The time to reach Cmax (Tmax)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
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The AUC during the dosing interval (AUCtau)
Časové okno: 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)
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The serum concentration at the end of the dosing interval (Ctrough)
Časové okno: 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)
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The elimination half-life (T1/2)
Časové okno: 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)
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The apparent volume of distribution (Vd/F)
Časové okno: 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)
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The apparent clearance (CL/F)
Časové okno: 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)
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Progression-free survival (PFS)
Časové okno: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
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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)
Časové okno: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
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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)
|
Spolupracovníci a vyšetřovatelé
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- HM-LIL2-101
- KEYNOTE-G39 (Jiný identifikátor: Merck & Sharp Dohme LLC)
- MK-3475-G39 (Jiný identifikátor: Merck & Sharp Dohme LLC)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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