STK-012 Monotherapy and in Combination Therapy in Patients with Solid Tumors
- Conditions
- Advanced Solid TumorMalignant MelanomaHead and Neck Squamous Cell CarcinomaMicrosatellite Instability HighGastric CancerNon Small Cell Lung CancerCervical CancerGastroEsophageal CancerUrothelial CarcinomaRenal Cell Carcinoma
- Interventions
- Registration Number
- NCT05098132
- Lead Sponsor
- Synthekine
- 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 therapy in patients with selected advanced solid tumors.
- Detailed Description
The phase 1a portion of the study is a dose escalation design to evaluate STK-012 as monotherapy and in combination therapy in patients with selected solid tumors. The phase 1b portion of the study includes dose expansions to evaluate STK-012 as monotherapy and in combination therapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 202
- Participants enrolled to STK-012 monotherapy dose escalation and expansion and STK-012 + pembrolizumab combination dose escalation must have selected tumor types and progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment.
- Participants enrolled to STK-012 + pembrolizumab combination dose expansion must have selected tumor types and may not have received treatment for metastatic disease.
- Participants enrolled to STK-012 dose escalation combination treatment with pembrolizumab, pemetrexed and carboplatin must have NSCLC and may not have received treatment for metastatic disease.
- Participants enrolled to STK-012 dose expansion combination treatment with pembrolizumab, pemetrexed and carboplatin must have PD-L1 negative NSCLC and may not have received treatment for metastatic disease.
Selected
- 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.
- Received radiotherapy within 2 weeks of the first dose of study treatment.
- Received prior IL-2-based or IL-15-based cytokine therapy.
- Participants with NSCLC may not have any known actionable genetic aberrations with approved therapies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: STK-012 weekly (QW) monotherapy dose escalation STK-012 STK-012 will be administered in sequential ascending doses as monotherapy subcutaneously (SC) QW until unacceptable toxicity, disease progression, or withdrawal of consent. Part B: STK-012 every three weeks (Q3W) monotherapy dose escalation STK-012 STK-012 will be administered in sequential ascending doses as monotherapy SC Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part C: STK-012 Q3W + pembrolizumab dose escalation STK-012 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. Part C: STK-012 Q3W + pembrolizumab dose escalation pembrolizumab 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. Part D: STK-012 Q3W monotherapy and STK-012 Q3W + pembrolizumab dose expansions STK-012 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. Part D: STK-012 Q3W monotherapy and STK-012 Q3W + pembrolizumab dose expansions pembrolizumab 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. Part E: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose escalation STK-012 STK-012 will be administered in sequential ascending doses SC Q3W in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part E: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose escalation pembrolizumab STK-012 will be administered in sequential ascending doses SC Q3W in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part E: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose escalation pemetrexed STK-012 will be administered in sequential ascending doses SC Q3W in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part E: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose escalation carboplatin STK-012 will be administered in sequential ascending doses SC Q3W in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part F: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose expansion STK-012 STK-012 will be administered at the RP2D SC in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part F: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose expansion pembrolizumab STK-012 will be administered at the RP2D SC in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part F: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose expansion pemetrexed STK-012 will be administered at the RP2D SC in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent. Part F: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose expansion carboplatin STK-012 will be administered at the RP2D SC in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.
- Primary Outcome Measures
Name Time Method Dose limiting toxicities (DLTs) 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 therapy
Adverse events 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 therapy 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.
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) 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 therapy
Progression-free survival (PFS) 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 therapy
Overall Survival (OS) 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 therapy
Area under the curve (AUC) of STK-012 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 therapy
Maximum concentration (Cmax) of STK-012 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 therapy
Time of maximum concentration (Tmax) of STK-012 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 therapy
Half-life (T1/2) of STK-012 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 therapy
Immunogenicity 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 therapy
Trial Locations
- Locations (19)
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
UCLA Hematology/Oncology - Santa Monica
🇺🇸Santa Monica, California, United States
Yale New Haven Hospital, Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Georgetown University
🇺🇸Washington, D.C., District of Columbia, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Columbia University Irving Medical Center
🇺🇸New York City, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Sarah Cannon Research Institute - Nashville
🇺🇸Nashville, Tennessee, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States