Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors

Locally Advanced/Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06414460
• Other study ID #: ISM3412-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: March 1, 2025
• Est. completion date: March 31, 2029

Study information

• Verified date: May 2024
• Source: InSilico Medicine Hong Kong Limited
• Contact: Yichen Liu
• Phone: +86 021-50831718
• Email: Insilico-Clinicaltrial[@]insilico.ai
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced/Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ISM3412
ISM3412 will be administered orally once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
InSilico Medicine Hong Kong Limited

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicity (DLT) events	To evaluate the safety and tolerability of ISM3412.	31 days
Primary	Incidence and severity of adverse events (AEs)	To evaluate the safety and tolerability of ISM3412.	Approximately 30 months
Primary	Recommended phase 2 dose (RP2D)	To determine the RP2D of ISM3412.	Approximately 30 months
Secondary	Maximum observed concentration (Cmax)	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412	Approximately 30 months
Secondary	Time of maximum observed concentration (Tmax)	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412	Approximately 30 months
Secondary	Area under the concentration-time curve (AUC)	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412	Approximately 30 months
Secondary	Terminal half-life (t1/2)	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412	Approximately 30 months
Secondary	Objective response rate (ORR)	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.	Approximately 30 months
Secondary	Best objective response (BOR)	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.	Approximately 30 months
Secondary	Duration of response (DoR)	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.	Approximately 30 months