Clinical trial NCT05598151: Dose Escalation and Expansion Study of HM97662 in Advanced or Metastatic Solid Tumors
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
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: 2022-10-28
Enrollment: 170
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 Phase1 study to assess the safety, PK, PD and efficacy of HM97662, EZH1/2 dual inhibitor, in solid tumors. The study is comprised of Dose-Escalation Part followed by randomized Dose-Ranging Part and Dose-Expansion Part. Dose-Escalation Part is planned with a 3+3 Dose-Escalation design and is to establish the MTD or RD for randomized Dose-Ranging Part. Dose-Ranging Part is designed mainly to further evaluate safety and preliminary efficacy of HM97662 monotherapy in subjects with specific genomic alterations to more precisely determine the potential RP2D that are to be tested in a Dose-Expansion Part. Dose-Expansion Part is designed to assess the potential efficacy of HM97662 monotherapy when administered at the RP2D to subjects in indication-specific expansion cohorts.


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 randomized dose-ranging and 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.
* For Dose-Ranging Part, documentation of an alteration in at least one of the genes of the SWI/SNF complex in tumor tissue (archival or newly obtained).

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.

Primary outcomes:
measure: Incidence and nature of DLTs
timeFrame: Days 1-28 of Cycle 1 (DLT assessment period) in Dose-Escalation Part
measure: Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI CTCAE v5.0
timeFrame: 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 outcomes:
measure: Area under the concentration-time curve (AUC)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: The maximum plasma concentration (Cmax)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Trough plasma concentration (Ctrough)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Time to reach Cmax (Tmax)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Terminal Half-life (T1/2)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Apparent clearance (CL/F)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Apparent volume of distribution (Vd/F)
timeFrame: until Cycle 4 Day1 (each cycle is 28 days)
measure: Objective response
timeFrame: 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)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Cancer Research SA
city: Ballarat
country: Australia
facility: Grampians Health
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Frankston
country: Australia
facility: Peninsula and Southeast Oncology
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul ST. Mary's Hospital
Study officials:
References: