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

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• 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)]
• Incidence and nature of DLTs [Time frame: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part]

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 during the dosing interval (AUCtau) [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 terminal half-life (T1/2) [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)]
• The apparent volume of distribution (Vd/F) [Time frame: Throughout the study until treatment discontinuation (up to 2-3 years)]
• Frequency of anti-drug antibodies (ADA) [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)]
• Duration of response (DOR) [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 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.

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.

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

United States · 5 centers

• Moffitt Cancer Center — Tampa
• The START Center for Cancer Care - Midwest — Grand Rapids
• Carl & Edyth Lindner Center for Research & Education at The Christ Hospital and The Christ — Cincinnati
• Mary Crowley Cancer Research — Dallas
• Mays Cancer Center at University of Texas Health San Antonio MD Anderson Cencer Center — San Antonio

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

Identifiers

NCT: NCT06234397 · BH-BAFP-101 · KEYNOTE-F89 · MK3475-F89

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗