Oral Administration of STC-15 in Subjects With Advanced Malignancies

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Advanced Solid Tumor; Advanced Cancer
• Intervention / Treatment: Drug: STC-15

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Melinda Snyder; Phone Number: 617-233-4057; Email: melinda.snyder@stormtherapeutics.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Honor Health
      • Contact: Mei Yu; Email: myu@honorhealth.com
      • Principal Investigator: Justin Moser, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Jordi Rodon Ahnert, M.D., PhD; Phone Number: 713-792-5603
      • Principal Investigator: Jordi Rodon Ahnert, M.D., PhD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics
      • Principal Investigator: Kyriakos Papadopoulos, MD
      • Contact: Isabel Jimenez; Phone Number: 210-593-5265; Email: Jimenez@startda.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of m6A modification of mRNA from peripheral blood	To evaluate the effect of STC-15 on METTL3 enzymatic activity	Screening through Cycle 2 (each cycle is 21 days)
Assessment of serum cytokines levels	To evaluate immunologic biomarkers in blood and tumor tissue	Screening through Cycle 2 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: STORM Therapeutics LTD
• Investigators: Study Director: Josefin Holz, STORM Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 21, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Oncology; METTL-3 Inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: STC15-22101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No