Clinical trial NCT05584111: Oral Administration of STC-15 in Subjects With Advanced Malignancies
Official title: Phase 1 Study to Evaluate the Safety, PK, PD, and Clinical Activity of STC-15, a METTL-3 Inhibitor, in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Advanced Solid Tumor
Cancer
Keywords: Oncology
METTL-3 Inhibitor
Lead sponsor: STORM Therapeutics LTD
Sponsor class: INDUSTRY
First posted: 2022-10-18
Enrollment: 42
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: 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.


Eligibility 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Screening through end of treatment, approximately 6 months
measure: Cmax (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Tmax (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Ctrough (PK)
timeFrame: Screening through end of treatment, approximately 6 months
measure: Terminal elimination half life (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: AUC (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Average concentration (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Systemic Clearance (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Volume of distribution at steady-state (PK)
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Accumulation ratio from first dose to steady-state (PK)
timeFrame: Screening through end of treatment, approximately 6 months
Secondary outcomes:
measure: Efficacy as measured by RECIST 1.1 (DoR)
timeFrame: Screening through disease progression, approximately 6 months
measure: Efficacy as measured by RECIST 1.1 (PFS)
timeFrame: Screening through disease progression, approximately 6 months
measure: Efficacy as measured by RECIST 1.1 (DCR)
timeFrame: Screening through disease progression, approximately 6 months
measure: Efficacy as measured by RECIST 1.1 (ORR)
timeFrame: Screening through disease progression, approximately 6 months
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Screening through 90 days after the last dose of STC-15, approximately 9 months
Other outcomes:
measure: Assessment of m6A modification of mRNA from peripheral blood
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
measure: Assessment of serum cytokines levels
timeFrame: Screening through Cycle 2 (each cycle is 21 days)
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
affiliation: STORM Therapeutics
name: Josefin Holz
role: STUDY_DIRECTOR
References: