Advanced Cancer, Advanced Solid Tumor, Cancer
Conditions
Keywords
Oncology, METTL-3 Inhibitor
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.
Interventions
DRUGSTC-15
STC-15 oral capsules various dosing regimen in 3-week cycles
Sponsors
STORM Therapeutics LTD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 * Adequate organ and marrow function * ECOG PS of 0 or 1 Key
Exclusion criteria
* Treatment with any local or systemic antineoplastic therapy within 3 weeks prior to first dose of STC-15 * Major surgery or radiation within the 3 weeks * Immune-related AEs from immunotherapy that required permanent discontinuation * Central nervous system (CNS) disease involvement, or prior history of Grade ≥3 drug-related CNS toxicity. * Active autoimmune disease that has required systemic treatment in the 2 years prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 (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 |
| 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of serum cytokines levels | Screening through Cycle 2 (each cycle is 21 days) | To evaluate immunologic biomarkers in blood and tumor tissue |
| 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 |
Countries
United States
Outcome results
None listed