Phase 1a/1b Study of STK-012 Monotherapy and in Combination With Pembrolizumab in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT05098132
• Recruitment Status: Recruiting
• First Posted: October 28, 2021
• Last Update Posted: January 12, 2024
• Sponsor: Synthekine
• Information provided by (Responsible Party): Synthekine

Tracking Information

• First Submitted Date: October 6, 2021
• First Posted Date: October 28, 2021
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: January 25, 2022
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 27, 2023)

• Dose limiting toxicities (DLTs) [ Time Frame: 1 cycle (21 days) ]
  Incidence of adverse events (AEs) meeting protocol defined DLT criteria and determination of the maximum tolerated dose (MTD) and/or the RP2D of STK-012 as a single agent and in combination with pembrolizumab
• Adverse events [ Time Frame: From 1st dose of STK-012 through 90 days after last dose of STK-012 ]
  Assess the safety and tolerability of STK-012 as monotherapy and in combination with pembrolizumab by review of AEs including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and adverse events resulting in death.

Original Primary Outcome Measures (submitted: October 20, 2021)

• Dose limiting toxicities (DLTs) [ Time Frame: 1 cycle (21 days) ]
  Incidence of adverse events (AEs) meeting protocol defined DLT criteria and determination of the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of STK-012 as a single agent and in combination with pembrolizumab
• Adverse events [ Time Frame: From 1st dose of STK-012 through 90 days after last dose of STK-012 ]
  Assess the safety and tolerability of STK-012 as monotherapy and in combination with pembrolizumab by review of AEs including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events leading to treatment discontinuation, and adverse events resulting in death.

Current Secondary Outcome Measures (submitted: July 22, 2022)

• Objective response rate (ORR) [ Time Frame: Up to 24 months ]
  The ORR is defined as the proportion of patients with confirmed CR or confirmed PR, based on RECIST Version 1.1 after STK-012 administration as monotherapy and in combination with pembrolizumab
• Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
  PFS is defined as the time from the start of treatment with STK-012 until the first documentation of disease progression or death due to any cause, whichever occurs first after STK-012 administration as monotherapy and in combination with pembrolizumab
• Overall Survival (OS) [ Time Frame: Up to 24 months ]
  Overall survival is defined as the time from the start of treatment with STK-012 until death due to any cause after STK-012 administration as monotherapy and in combination with pembrolizumab
• Area under the curve (AUC) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The AUC of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Maximum concentration (Cmax) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The Cmax of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Time of maximum concentration (Tmax) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The Tmax of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Half-life (T1/2) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The T1/2 of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Immunogenicity [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The immunogenicity of STK-012 will be assessed by summarizing the number of patients who develop detectable anti-drug antibodies (ADAs) at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab

Original Secondary Outcome Measures (submitted: October 20, 2021)

• Objective response rate (ORR) [ Time Frame: Up to 24 months ]
  The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1 after STK-012 administration as monotherapy and in combination with pembrolizumab
• Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
  PFS is defined as the time from the start of treatment with STK-012 until the first documentation of disease progression or death due to any cause, whichever occurs first after STK-012 administration as monotherapy and in combination with pembrolizumab
• Overall Survival (OS) [ Time Frame: Up to 24 months ]
  Overall survival is defined as the time from the start of treatment with STK-012 until death due to any cause after STK-012 administration as monotherapy and in combination with pembrolizumab
• Area under the curve (AUC) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The AUC of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Maximum concentration (Cmax) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The Cmax of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Time of maximum concentration (Tmax) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The Tmax of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Half-life (T1/2) of STK-012 [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The T1/2 of STK-012 will be measured at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab
• Immunogenicity [ Time Frame: From 1st dose of STK-012 through 30 days after last dose of STK-012 ]
  The immunogenicity of STK-012 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs) at different timepoints after STK-012 administration as monotherapy and in combination with pembrolizumab

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1a/1b Study of STK-012 Monotherapy and in Combination With Pembrolizumab in Patients With Solid Tumors
• Official Title: A Phase 1a/1b Study to Evaluate the Safety and Tolerability of STK-012 Monotherapy and in Combination With Pembrolizumab in Patients With Selected Advanced Solid Tumors
• Brief Summary: This is a first-in-human, phase 1a/1b, multicenter, open-label, dose escalation study of STK-012 as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors.
• Detailed Description: The phase 1a portion of the study is standard 3+3 dose escalation design to evaluate STK-012 as monotherapy and in combination with pembrolizumab in patients with selected solid tumors who have progressed after standard of care treatments. The phase 1b portion of the study includes dose expansions to evaluate STK-012 as monotherapy and in combination with pembrolizumab at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumor
• Non Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma
• Malignant Melanoma
• Renal Cell Carcinoma
• Cervical Cancer
• Microsatellite Instability High
• Gastric Cancer
• GastroEsophageal Cancer
• Urothelial Carcinoma
• Mismatch Repair Deficiency

Intervention

• Drug: STK-012
  pegylated alpha/beta-biased engineered interleukin-2
• Drug: Pembrolizumab
  anti-PD-1 humanized monoclonal antibody

Study Arms

• Experimental: Part A: STK-012 weekly (QW) monotherapy dose escalation
  STK-012 will be administered in sequential ascending doses as monotherapy subcutaneously (SC) QW until unacceptable toxicity, disease progression, or withdrawal of consent.
  Intervention: Drug: STK-012
• Experimental: Part B: STK-012 every three weeks (Q3W) monotherapy dose escalation
  STK-012 will be administered in sequential ascending doses as monotherapy SC Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.
  Intervention: Drug: STK-012
• Experimental: Part C: STK-012 Q3W + pembrolizumab dose escalation
  STK-012 will be administered in sequential ascending doses SC Q3W in combination with a fixed dose of pembrolizumab intravenously (IV) Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.
  Interventions:

  • Drug: STK-012
  • Drug: Pembrolizumab
• Experimental: Part D: Dose expansions
  STK-012 will be administered at the RP2D SC as monotherapy and in combination with a fixed dose of pembrolizumab IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.
  Interventions:

  • Drug: STK-012
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 22, 2022): 202
• Original Estimated Enrollment (submitted: October 20, 2021): 135
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Selected Inclusion Criteria

1. Patients must have selected tumor types and must have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment.
2. Patients must be amenable to a fresh tissue biopsy, unless medically contraindicated.
3. Patients with central nervous system (CNS) metastases must have been treated and be asymptomatic.

Selected Exclusion Criteria:

1. Received systemic anti-cancer therapy within 3 weeks of the first dose of study treatment or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment.
2. Received radiotherapy within 2 weeks of the first dose of study treatment.
3. Received prior IL-2-based or IL-15-based cytokine therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Operations; 650-271-9888; clinicaltrialinfo@synthekine.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05098132
• Other Study ID Numbers: STK-012-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Synthekine
• Original Responsible Party: Same as current
• Current Study Sponsor: Synthekine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Synthekine
• Verification Date: November 2023