Advanced or Metastatic Solid Tumors
Conditions
Brief summary
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.
Interventions
DRUGHM16390
HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle
DRUGpembrolizumab
Fixed dose of pembrolizumab will be administered as an IV infusion over 30 minutes on Day 1 of every 3-week treatment cycle
Sponsors
Merck Sharp & Dohme LLC
Hanmi Pharmaceutical Company Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
1. Dose-Escalation Part: Divided into 2 arms (Arm A: HM16390 monotherapy, Arm B: HM16390 in combination with pembrolizumab) 2. Dose-Ranging Part: Subjects will be randomized 1:1 into at least two dose levels to enable better selection of the doses for further evaluation, and may apply to cohorts of both monotherapy and combination therapy 3. Dose-Expansion Part: Based on the available data from Dose-Escalation and Dose-Ranging parts, the most feasible dose will be selected as the RDE and will be administered to subjects in indication-specific expansion cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and nature of DLTs | 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 |
| Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The area under the concentration-time curve from time 0 to the last observable concentration (AUClast) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The AUC extrapolated to infinity (AUCinf) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The AUC during the dosing interval (AUCtau) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The serum concentration at the end of the dosing interval (Ctrough) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The elimination half-life (T1/2) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The maximum serum concentration (Cmax) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The apparent clearance (CL/F) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| Objective response rate (ORR) | 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 |
| Disease Control Rate (DCR) | 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 |
| Progression-free survival (PFS) | 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 |
| Duration of response (DOR) | 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. |
| The apparent volume of distribution (Vd/F) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
| The time to reach Cmax (Tmax) | Throughout the study until treatment discontinuation (up to 2-3 years) | To evaluate PK profile upon HM16390 administration |
Countries
South Korea, United States
Contacts
Primary ContactYoung Su (Bobby) Noh
Outcome results
None listed