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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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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 / Treatment
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* Drug: STK-012
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Selected Inclusion Criteria Patients must have selected tumor types and must have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment. Patients must be amenable to a fresh tissue biopsy, unless medically contraindicated. 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 radiotherapy within 2 weeks of the first dose of study treatment. Received prior IL-2-based or IL-15-based cytokine therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: STK-012 weekly (QW) monotherapy dose escalation<br>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<br>* pegylated alpha/beta-biased engineered interleukin-2<br>|
| Experimental: Part B: STK-012 every three weeks (Q3W) monotherapy dose escalation<br>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<br>* pegylated alpha/beta-biased engineered interleukin-2<br>|
| Experimental: Part C: STK-012 Q3W + pembrolizumab dose escalation<br>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<br>* pegylated alpha/beta-biased engineered interleukin-2<br>Drug: Pembrolizumab<br>* anti-PD-1 humanized monoclonal antibody<br>|
| Experimental: Part D: Dose expansions<br>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<br>* pegylated alpha/beta-biased engineered interleukin-2<br>Drug: Pembrolizumab<br>* anti-PD-1 humanized monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) | 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 | 1 cycle (21 days) | 
| Adverse events | 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. | From 1st dose of STK-012 through 90 days after last dose of STK-012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | 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 | Up to 24 months | 
| Progression-free survival (PFS) | 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 | Up to 24 months | 
| Overall Survival (OS) | 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 | Up to 24 months | 
| Area under the curve (AUC) 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 | From 1st dose of STK-012 through 30 days after last dose of STK-012 | 
| Maximum concentration (Cmax) 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 | From 1st dose of STK-012 through 30 days after last dose of STK-012 | 
| Time of maximum concentration (Tmax) 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 | From 1st dose of STK-012 through 30 days after last dose of STK-012 | 
| Half-life (T1/2) 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 | From 1st dose of STK-012 through 30 days after last dose of STK-012 | 
| Immunogenicity | 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 | From 1st dose of STK-012 through 30 days after last dose of STK-012 |