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

Official title

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

Overview

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

• Drug HM16390
  HM16390 will be administered subcutaneously using syringes on Day 1 of every 3-week treatment cycle
• 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

Primary outcome measures

• Incidence and nature of DLTs [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. [Time frame: Throughout the study until end of safety follow-up period (90 days after the last treatment)]

Secondary outcome measures (12)

• 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)]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 5 centers

• Seoul National University Bundang Hospital — Seongnam-si
• Seoul National University Hospital — Seoul
• Severance Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

United States · 2 centers

• Massachusetts General Hospital — Boston
• Karmanos Cancer Institute — Detroit

Identifiers

NCT: NCT06724016 · HM-LIL2-101 · KEYNOTE-G39 · MK-3475-G39

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗