HM16390:n annoksen suurennus- ja laajennustutkimus pitkälle edenneissä tai metastaattisissa kiinteissä kasvaimissa
Vaihe I, avoin, monikeskus, HM16390:n annoksen eskalaatio- ja laajennustutkimus potilailla, joilla on edennyt tai metastaattinen kiinteä kasvain
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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Hyebin Son
- Puhelinnumero: 82-2-410-9835
- Sähköposti: hyebin.son@hanmi.co.kr
Opiskelupaikat
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Seoul, Etelä -Korea, 03080
- Rekrytointi
- Seoul National University Hospital
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Seoul, Etelä -Korea, 06351
- Rekrytointi
- Samsung Medical Center
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Seoul, Etelä -Korea, 03722
- Rekrytointi
- Severance Hospital
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Seoul, Etelä -Korea, 05505
- Aktiivinen, ei rekrytointi
- Asan Medical Center
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Gyeonggi-do
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Seongnam-si, Gyeonggi-do, Etelä -Korea, 13620
- Rekrytointi
- Seoul National University Bundang Hospital
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California
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Los Angeles, California, Yhdysvallat, 90095
- Rekrytointi
- 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, Yhdysvallat, 02114
- Rekrytointi
- Massachusetts General Hospital
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Michigan
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Detroit, Michigan, Yhdysvallat, 48201
- Rekrytointi
- Karmanos Cancer Institute
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: HM16390
HM16390 Monotherapy |
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
|
Kokeellinen: 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
Muut nimet:
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Incidence and nature of DLTs
Aikaikkuna: 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.
Aikaikkuna: 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)
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Objective response rate (ORR)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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 area under the concentration-time curve from time 0 to the last observable concentration (AUClast)
Aikaikkuna: 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 extrapolated to infinity (AUCinf)
Aikaikkuna: 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 during the dosing interval (AUCtau)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
|
|
Duration of response (DOR)
Aikaikkuna: 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)
|
Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
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- MK-3475-G39 (Muu tunniste: Merck & Sharp Dohme LLC)
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