Phase I Study of HM16390 as a Single Agent and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

• Conditions: Advanced or Metastatic Solid Tumors
• Interventions: Drug: HM16390; Drug: pembrolizumab

• Registration Number: NCT06724016
• Lead Sponsor: Hanmi Pharmaceutical Company Limited

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-29
• Study First Submitted QC: 2024-12-06
• Study First Posted: 2024-12-09
• Study Start: 2024-12-11
• Status Verified: 2025-11
• Last Update Submitted: 2025-11-17
• Last Update Posted: 2025-11-20
• Primary Completion: 2031-07
• Study Completion: 2031-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 292

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HM16390	HM16390	HM16390 Monotherapy
HM16390 + pembrolizumab	HM16390	HM16390 in combination with pembrolizumab
HM16390 + pembrolizumab	pembrolizumab	HM16390 in combination with pembrolizumab

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
The maximum serum concentration (Cmax)	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 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 apparent clearance (CL/F)	Throughout the study until treatment discontinuation (up to 2-3 years)	To evaluate PK profile upon HM16390 administration
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
The time to reach Cmax (Tmax)	Throughout the study until treatment discontinuation (up to 2-3 years)	To evaluate PK profile upon HM16390 administration
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 elimination half-life (T1/2)	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
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.

Trial Locations

Locations (7)

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, South Korea

Severance Hospital; 🇰🇷 Seoul, South Korea

Asan Medical Center; 🇰🇷 Seoul, South Korea

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Seoul National University Hospital; 🇰🇷 Seoul, South Korea

Samsung Medical Center; 🇰🇷 Seoul, South Korea