Phase 1a/1b Study of STK-012 Monotherapy and in Combination With Pembrolizumab in Patients With Solid Tumors
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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 recommended phase 2 dose (RP2D) in selected solid tumor types.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
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. |
Drug: STK-012
pegylated alpha/beta-biased engineered interleukin-2
|
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. |
Drug: STK-012
pegylated alpha/beta-biased engineered interleukin-2
|
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. |
Drug: STK-012
pegylated alpha/beta-biased engineered interleukin-2
Drug: Pembrolizumab
anti-PD-1 humanized monoclonal antibody
|
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. |
Drug: STK-012
pegylated alpha/beta-biased engineered interleukin-2
Drug: Pembrolizumab
anti-PD-1 humanized monoclonal antibody
|
Outcome Measures
Primary Outcome Measures
- 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 recommended Phase 2 dose (RP2D) of STK-012 as a single agent and in combination with pembrolizumab
- 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 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.
Secondary Outcome Measures
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
- 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 with pembrolizumab
Eligibility Criteria
Criteria
Selected Inclusion Criteria
-
In dose-escalation (Phase 1a), patients must have selected tumor types and must have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment
-
Available archived tumor tissue sample. In the setting where archival material is unavailable or unsuitable for use, the patient must consent and undergo fresh tumor biopsy. In some patients, a new pre-treatment and on-treatment tumor biopsy may be required.
-
Patients with central nervous system (CNS) metastases must have been treated and be asymptomatic.
Selected Exclusion Criteria:
-
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 definitive radiotherapy within 2 weeks of the first dose of study treatment; or palliative radiotherapy (defined as < 2 weeks of radiotherapy to non-central nervous system [CNS] disease) within 1 week of the first dose of study treatment.
-
Received prior IL-2-based or IL-15-based cytokine therapy
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Columbia University Irving Medical Center | New York | New York | United States | 10032 |
2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
3 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
4 | Sarah Cannon Research Institute - Nashville | Nashville | Tennessee | United States | 37203 |
5 | NEXT Virginia | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Synthekine
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STK-012-101