Oral Administration of STC-15 in Subjects With Advanced Malignancies
Study Details
Study Description
Brief Summary
This Phase 1, multi-center, open-label, first-in-human study evaluates multiple ascending daily oral doses of STC-15 in Q3W treatment cycles in a 3+3 cohort design with dose levels determined by a modified Fibonacci algorithm. The study is designed to systematically assess safety and tolerability, pharmacokinetics, pharmacodynamics and clinical activity of STC-15 in adult subjects with advanced malignancies. Dose levels for further evaluation in expansion cohorts will be selected based on all available PK, pharmacodynamic, target engagement, efficacy, safety, and tolerability data including long-term safety data beyond dose limiting toxicities (DLTs). The study may be amended to evaluate STC-15 in combination with a Food and Drug Administration-approved standard of care treatment regimen, which could encompass targeted/chemotherapy, radiation therapy and/or immunotherapy with immune checkpoint blockers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Level 1 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 2 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 3 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 4 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 5 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 6 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
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| Experimental: Dose Level 7 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
|
| Experimental: Dose Level 8 30mg and 100mg capsules, daily administration for 3 week (21 day) cycles |
Drug: STC-15
STC-15 oral capsules once a day in 3-week cycles
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events [Screening through end of treatment, approximately 6 months]
To evaluate the incidence, severity, and duration of adverse events
- Cmax (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the Cmax concentration over a dosing interval, systemic clearance, volume of distribution at steady-state (Vss), and accumulation ratio from first dose to steady-state.
- Tmax (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the time to Cmax (Tmax)
- Ctrough (PK) [Screening through end of treatment, approximately 6 months]
To determine observed trough serum concentration (Ctrough)
- Terminal elimination half life (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the terminal elimination half-life (t½)
- AUC (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine AUC in 1 dosing interval
- Average concentration (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the average concentration over a dosing interval
- Systemic Clearance (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the systemic clearance
- Volume of distribution at steady-state (PK) [Screening through Cycle 2 (each cycle is 21 days)]
To determine the volume of distribution at steady-state (Vss)
- Accumulation ratio from first dose to steady-state (PK) [Screening through end of treatment, approximately 6 months]
To determine the accumulation ratio from first dose to steady-state
Secondary Outcome Measures
- Efficacy as measured by RECIST 1.1 (DoR) [Screening through disease progression, approximately 6 months]
Determine the duration of response (DoR)
- Efficacy as measured by RECIST 1.1 (PFS) [Screening through disease progression, approximately 6 months]
Determine progression-free survival (PFS)/PFS assessed per immune-related response evaluation criteria (iPFS).
- Efficacy as measured by RECIST 1.1 (DCR) [Screening through disease progression, approximately 6 months]
Determine the disease control rate (DCR)
- Efficacy as measured by RECIST 1.1 (ORR) [Screening through disease progression, approximately 6 months]
Determine the objective response rate (ORR)
- Recommended Phase 2 Dose (RP2D) [Screening through 90 days after the last dose of STC-15, approximately 9 months]
determine the RP2D for STC-15
Other Outcome Measures
- Assessment of m6A modification of mRNA from peripheral blood [Screening through Cycle 2 (each cycle is 21 days)]
To evaluate the effect of STC-15 on METTL3 enzymatic activity
- Assessment of serum cytokines levels [Screening through Cycle 2 (each cycle is 21 days)]
To evaluate immunologic biomarkers in blood and tumor tissue
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
18 years of age
-
Histologic or cytologic confirmation of advanced malignancy that has failed standard of care (SOC) therapy and no further SOC therapy is available or the subject has declined additional SOC therapy
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Adequate organ and marrow function
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ECOG PS of 0 or 1
Key Exclusion Criteria:
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Treatment with any local or systemic antineoplastic therapy within 3 weeks prior to first dose of STC-15
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Major surgery or radiation within the 3 weeks
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Immune-related AEs from immunotherapy that required permanent discontinuation
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Central nervous system (CNS) disease involvement, or prior history of Grade ≥3 drug-related CNS toxicity.
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Active autoimmune disease that has required systemic treatment in the 2 years prior to Screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Honor Health | Scottsdale | Arizona | United States | 85258 |
| 2 | South Texas Accelerated Research Therapeutics | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- STORM Therapeutics LTD
Investigators
- Study Director: Josefin Holz, STORM Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STC15-22101