Dose Escalation and Expansion Study of HM97662 in Advanced or Metastatic Solid Tumors

A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study of HM97662 as a Single Agent in Patients With Advanced or Metastatic Solid Tumors

This is a Phase1 study to assess the safety, PK, PD and efficacy of HM97662, EZH1/2 dual inhibitor, in solid tumors. The study will be conducted in Dose-Escalation and Dose-Expansion parts. Dose-Escalation Part is planned with a 3+3 Dose-Escalation design and is to establish the MTD or RD for Dose-Expansion part of HM97662 as a single agent in subjects with advanced or metastatic solid tumors. Dose-Expansion Part is designed to assess the potential efficacy of HM97662 monotherapy 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: HM97662

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiyeon Yoon; Phone Number: 82-2-410-0368; Email: mush1223@hanmi.co.kr

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Cancer Research Sa
  • Ballarat, Australia
    • Recruiting
    • Grampians Health
  • Clayton, Australia
    • Recruiting
    • Monash Medical Centre
  • Frankston, Australia
    • Recruiting
    • Peninsula and Southeast Oncology
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea, Seoul ST. Mary's Hospital.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically and/or cytologically confirmed advanced or metastatic solid tumor who have failed/are intolerant to standard therapy.
• Patients for dose-escalation part must have evaluable or measurable disease at baseline and the patients for dose-expansion part must have at least one measurable lesion at baseline by CT or MRI per Response Evaluation Criteria in Solid Tumor (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months before starting HM97662.
• Adequate renal function.
• Adequate hematologic function.
• Adequate liver function.
• Males or females aged ≥ 18 years (or country's legal age of majority if the legal age was > 18 years) at the time of informed consent.

Exclusion Criteria:

• Prior exposure to valemetostat or other EZH1/2 dual inhibitor.
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms.
• Patients currently taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers.
• 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.
• Major surgery within 4 weeks before the first dose of study drug treatment in Cycle 1.
• Females who are pregnant or breastfeeding.
• Patients who have undergone an organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HM97662; Tablet, oral administration, once daily (QD), continuous dosing	Drug: HM97662; To evaluate the safety, tolerability, preliminary anti-tumor efficacy, PK and PD of HM97662 in solid tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of DLTs	Days 1-28 of Cycle 1 (DLT assessment period) in Dose-Escalation Part
Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI CTCAE v5.0	until Safety Follow-up, 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve (AUC)	until Cycle 4 Day1 (each cycle is 28 days)
The maximum plasma concentration (Cmax)	until Cycle 4 Day1 (each cycle is 28 days)
Trough plasma concentration (Ctrough)	until Cycle 4 Day1 (each cycle is 28 days)
Time to reach Cmax (Tmax)	until Cycle 4 Day1 (each cycle is 28 days)
Terminal Half-life (T1/2)	until Cycle 4 Day1 (each cycle is 28 days)
Apparent clearance (CL/F)	until Cycle 4 Day1 (each cycle is 28 days)
Apparent volume of distribution (Vd/F)	until Cycle 4 Day1 (each cycle is 28 days)
Objective response	Day 1 of Cycles 3, 5, 7 (each cycle is 28 days) and further (every 8 weeks) until disease progression (assessed up to 5 years)

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HM-EZHI-101

Drug and device information, study documents

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