Oral Administration of STC-15 in Subjects With Advanced Malignancies

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1 Study to Evaluate the Safety, PK, PD, and Clinical Activity of STC-15, a METTL-3 Inhibitor, in Subjects With Advanced Malignancies

Conditions
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Advanced Cancer, Advanced Solid Tumor, Cancer

Intervention / Treatment
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* Drug: STC-15


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>30mg capsules, daily administration for 3 week (21 day) cycles | Drug: STC-15<br>* STC-15 oral capsules various dosing regimen in 3-week cycles<br>* Other names: METTL-3 Inhibitor;|
| Experimental: Dose Level 2<br>30mg capsules, MWF administration for 3 week (21 day) cycles | Drug: STC-15<br>* STC-15 oral capsules various dosing regimen in 3-week cycles<br>* Other names: METTL-3 Inhibitor;|
| Experimental: Dose Level 3<br>100mg capsules, MWF administration for 3 week (21 day) cycles | Drug: STC-15<br>* STC-15 oral capsules various dosing regimen in 3-week cycles<br>* Other names: METTL-3 Inhibitor;|
| Experimental: Dose Level 4<br>30mg and 100mg capsules, M-MWF administration for 3 week (21 day) cycles | Drug: STC-15<br>* STC-15 oral capsules various dosing regimen in 3-week cycles<br>* Other names: METTL-3 Inhibitor;|
| Experimental: Dose Level 5<br>30mg and 100mg capsules, M-MWF administration for 3 week (21 day) cycles | Drug: STC-15<br>* STC-15 oral capsules various dosing regimen in 3-week cycles<br>* Other names: METTL-3 Inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | To evaluate the incidence, severity, and duration of adverse events | Screening through end of treatment, approximately 6 months | 
| Cmax (PK) | 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. | Screening through Cycle 2 (each cycle is 21 days) | 
| Tmax (PK) | To determine the time to Cmax (Tmax) | Screening through Cycle 2 (each cycle is 21 days) | 
| Ctrough (PK) | To determine observed trough serum concentration (Ctrough) | Screening through end of treatment, approximately 6 months | 
| Terminal elimination half life (PK) | To determine the terminal elimination half-life (t½) | Screening through Cycle 2 (each cycle is 21 days) | 
| AUC (PK) | To determine AUC in 1 dosing interval | Screening through Cycle 2 (each cycle is 21 days) | 
| Average concentration (PK) | To determine the average concentration over a dosing interval | Screening through Cycle 2 (each cycle is 21 days) | 
| Systemic Clearance (PK) | To determine the systemic clearance | Screening through Cycle 2 (each cycle is 21 days) | 
| Volume of distribution at steady-state (PK) | To determine the volume of distribution at steady-state (Vss) | Screening through Cycle 2 (each cycle is 21 days) | 
| Accumulation ratio from first dose to steady-state (PK) | To determine the accumulation ratio from first dose to steady-state | Screening through end of treatment, approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as measured by RECIST 1.1 (DoR) | Determine the duration of response (DoR) | Screening through disease progression, approximately 6 months | 
| Efficacy as measured by RECIST 1.1 (PFS) | Determine progression-free survival (PFS)/PFS assessed per immune-related response evaluation criteria (iPFS). | Screening through disease progression, approximately 6 months | 
| Efficacy as measured by RECIST 1.1 (DCR) | Determine the disease control rate (DCR) | Screening through disease progression, approximately 6 months | 
| Efficacy as measured by RECIST 1.1 (ORR) | Determine the objective response rate (ORR) | Screening through disease progression, approximately 6 months | 
| Recommended Phase 2 Dose (RP2D) | determine the RP2D for STC-15 | Screening through 90 days after the last dose of STC-15, approximately 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, METTL-3 Inhibitor