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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Advanced or Metastatic Solid Tumors

Intervention / Treatment
-----------------
* Drug: HM97662


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) |