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

Sponsor
Synthekine (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05098132
Collaborator
(none)
202
5
4
44.2
40.4
0.9

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.

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

Study Type:
Interventional
Anticipated Enrollment :
202 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 25, 2022
Anticipated Primary Completion Date :
Oct 1, 2025
Anticipated Study Completion Date :
Oct 1, 2025

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

  1. 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

  2. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Selected Inclusion Criteria

  1. 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

  2. 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.

  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 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.

  3. 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.
Responsible Party:
Synthekine
ClinicalTrials.gov Identifier:
NCT05098132
Other Study ID Numbers:
  • STK-012-101
First Posted:
Oct 28, 2021
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 27, 2022