Clinical trial NCT06724016: Dose Escalation and Expansion Study of HM16390 in Advanced or Metastatic Solid Tumors
Official title: A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study of HM16390 in Patients with Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Lead sponsor: Hanmi Pharmaceutical Company Limited
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a First-in-Human, Phase 1, Dose-Escalation and Dose-Expansion study of HM16390, as a single agent 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 at each dose level. After a comprehensive review of available data from both Dose-Escalation Part and Dose-Ranging Part, the potential RP2D to be tested in the Dose-Expansion Part is determined. Dose-Expansion Part is designed to assess the potential efficacy of HM16390 as a single agent when administered at the potential RP2D to subjects in indication-specific expansion cohorts.


Eligibility 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.
* 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 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.

Primary outcomes:
measure: Incidence and nature of DLTs
timeFrame: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
measure: Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
timeFrame: Throughout the study until end of safety follow-up period (90 days after the last treatment)
Secondary outcomes:
measure: The maximum serum concentration (Cmax)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The time to reach Cmax (Tmax)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The area under the concentration-time curve from time 0 to the last observable concentration (AUClast)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The AUC extrapolated to infinity (AUCinf)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The AUC during the dosing interval (AUCtau)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The elimination half-life (T1/2)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The apparent volume of distribution (Vd/F)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: The apparent clearance (CL/F)
timeFrame: Throughout the study until treatment discontinuation (up to 2-3 years)
measure: Objective response rate (ORR)
timeFrame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
measure: Disease Control Rate (DCR)
timeFrame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
measure: Progression-free survival (PFS)
timeFrame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
measure: Duration of response (DOR)
timeFrame: Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: