Dose Escalation and Expansion Study of HM16390 Alone or With Pembrolizumab in Advanced or Metastatic Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: pembrolizumab; Drug: HM16390

• Study Type: Interventional
• Enrollment (Estimated): 292
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Young Su (Bobby) Noh; Phone Number: 82-2-410-9277; Email: 63forever@hanmi.co.kr

Study Locations

• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Asan Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HM16390; HM16390 Monotherapy	Drug: HM16390; HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle
Experimental: HM16390 + pembrolizumab; HM16390 in combination with pembrolizumab	Drug: pembrolizumab; Fixed dose of pembrolizumab will be administered as an IV infusion over 30 minutes on Day 1 of every 3-week treatment cycle; Other Names: KEYTRUDA®; Drug: HM16390; HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of DLTs	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
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	Throughout the study until end of safety follow-up period (90 days after the last treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	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)	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)
The maximum serum concentration (Cmax)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The time to reach Cmax (Tmax)	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)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The AUC extrapolated to infinity (AUCinf)	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)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The serum concentration at the end of the dosing interval (Ctrough)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The elimination half-life (T1/2)	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)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The apparent clearance (CL/F)	To evaluate PK profile upon HM16390 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
Progression-free survival (PFS)	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)	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)

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2024
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: November 29, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; pembrolizumab
• Other Study ID Numbers: HM-LIL2-101; KEYNOTE-G39 (Other Identifier: Merck & Sharp Dohme LLC); MK-3475-G39 (Other Identifier: Merck & Sharp Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No