A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study of HM16390, as a Single Agent and in Combination With Pembrolizumab, in Patients With Advanced or Metastatic Solid Tumors
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.
Arms & 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
Outcome measures
Primary
Incidence and nature of DLTs
To evaluate safety and tolerability of HM16390 as a single agent and in combination with pembrolizumab
Time frame: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
To evaluate safety and tolerability of HM16390 as a single agent, and in combination with pembrolizumab
Time frame: Throughout the study until end of safety follow-up period (90 days after the last treatment)
Secondary
The maximum serum concentration (Cmax)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The time to reach Cmax (Tmax)
Time frame: 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)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The AUC extrapolated to infinity (AUCinf)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The AUC during the dosing interval (AUCtau)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The serum concentration at the end of the dosing interval (Ctrough)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The elimination half-life (T1/2)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The apparent volume of distribution (Vd/F)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
The apparent clearance (CL/F)
Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)
Objective response rate (ORR)
Time frame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Disease Control Rate (DCR)
Time frame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Progression-free survival (PFS)
Time frame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Duration of response (DOR)
Time frame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Eligibility criteria
Study locations (2)
Massachusetts General Hospital
Boston, Massachusetts, 02114
Karmanos Cancer Institute
Detroit, Michigan, 48201