Clinical trial NCT06414460: Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced/Metastatic Solid Tumors
Keywords: Methionine adenosyltransferase 2A (MAT2A)
homozygous MTAP deletion
MAT2A inhibitor
ISM3412
Lead sponsor: InSilico Medicine Hong Kong Limited
Sponsor class: INDUSTRY
First posted: 2024-05-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study has consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2). The primary objectives of this study are to evaluate the safety and tolerability of ISM3412 in participants with locally advanced/metastatic solid tumors, and to determine the RP2D of ISM3412.


Eligibility criteria: Inclusion Criteria:

1. Male or female participants with age ≥18 years at the time of signing the informed consent.
2. Histologically confirmed unresectable locally advanced or metastatic solid tumors with confirmed homozygous MTAP deletion, who have disease progression after standard therapy, intolerable to standard therapy, or for whom no standard therapy exists.
3. Have measurable or evaluable lesions in Part 1 and at least one measurable target lesion in Part 2 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
4. Participants must provide a documentary evidence of homozygous MTAP deletion; or provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or at least 15 FFPE tumor tissue slides, or perform tumor tissue biopsies for a confirmatory genetic test indicating homozygous MTAP deletion.
5. ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
6. Life expectancy of ≥12 weeks as judged by the investigator.
7. Adequate organ function as determined by medical assessment.
8. Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.

Exclusion Criteria:

1. Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
2. Participation in other therapeutic clinical studies within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
3. Anti-tumor therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogues, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter prior to first dose of study treatment.
4. Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
5. History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
6. Previous history of, or presence of Gilbert's syndrome.
7. Previous history of myelodysplastic syndrome.
8. Prior solid organ or hematopoietic stem cell transplant.
9. Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
10. Have serious cardiovascular or cerebrovascular disease as per protocol.
11. Presence of uncontrolled systemic infection as per protocol.
12. Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition.

Other protocol inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLT) events
timeFrame: 31 days
measure: Incidence and severity of adverse events (AEs)
timeFrame: Approximately 30 months
measure: Recommended phase 2 dose (RP2D)
timeFrame: Approximately 30 months
Secondary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Approximately 30 months
measure: Time of maximum observed concentration (Tmax)
timeFrame: Approximately 30 months
measure: Area under the concentration-time curve (AUC)
timeFrame: Approximately 30 months
measure: Terminal half-life (t1/2)
timeFrame: Approximately 30 months
measure: Objective response rate (ORR)
timeFrame: Approximately 30 months
measure: Best objective response (BOR)
timeFrame: Approximately 30 months
measure: Duration of response (DoR)
timeFrame: Approximately 30 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
Study officials:
References: