Dose Escalation and Expansion Study of BH3120 Alone or With Pembrolizuamb in Advanced or Metastatic Solid Tumors

A Phase I, Open-Label, Multinational, Multicenter, Dose Escalation and Expansion Study of BH3120, 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 BH3120, 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 RD for Dose-Expansion part, while Dose-Expansion part is designed to assess potential efficacy of BH3120, as a single agent and in combination with pembrolizumab, when administered at the RD to subjects in indication-specific expansion cohorts.

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: BH3120; Drug: pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 245
• 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, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • The START Center for Cancer Care - Midwest
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • Carl & Edyth Lindner Center for Research & Education at The Christ Hospital and The Christ Hospital Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Withdrawn
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cencer Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Have a Histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy.
• PD-L1 positive expression (Tumor Proportion Score ≥1% or Combined Positive Score ≥1).
• Have at least one lesion, not previously irradiated that can be accurately measured per RECIST version 1.1.
• 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 Hematologic and liver function.

Key Exclusion Criteria:

• Has received prior therapy with an anti-4-1BB(CD137) agent.
• Known active CNS metastases and/or carcinomatous meningitis.
• Known additional malignancy that is progressing or has required active treatment.
• History of chronic liver disease or evidence of hepatic cirrhosis.
• History of severe toxicities associated with a prior immunotherapy.
• 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.

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: BH3120; Arm A: BH3120 Monotherapy	Drug: BH3120; BH3120 will be administered as an IV infusion over 90 minutes on Day 1 of every 3-week treatment cycle
Experimental: BH3120 + pembrolizumab; Arm B: BH3120 in combination with pembrolizumab	Drug: BH3120; BH3120 will be administered as an IV infusion over 90 minutes 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; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.	To evaluate safety and tolerability of BH3120 as a single agent and in combination with pembrolizumab administration	Throughout the study until end of safety follow-up period (90 days after the last treatment)
Incidence and nature of DLTs	To evaluate safety and tolerability of BH3120 as a single agent and in combination with pembrolizumab administration	At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum serum concentration (Cmax)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The time to reach Cmax (Tmax)	To evaluate PK profile upon BH3120 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 BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The AUC during the dosing interval (AUCtau)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The AUC extrapolated to infinity (AUCinf)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The terminal half-life (T1/2)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The apparent clearance (CL/F)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
The apparent volume of distribution (Vd/F)	To evaluate PK profile upon BH3120 administration	Throughout the study until treatment discontinuation (up to 2-3 years)
Frequency of anti-drug antibodies (ADA)	Immunogenicity of BH3120	Throughout the study until treatment discontinuation (up to 2-3 years)
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)
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 v. 1.1 or death from any cause, whichever occurs first.	Throughout the study until disease progression or death whichever occurs first (up to 2-3 years)
Progression-free survival (PFS)	PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v.1.1 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)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: BH-BAFP-101; KEYNOTE-F89 (Other Identifier: Merck Sharp & Dohme LLC); MK3475-F89 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No