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RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2 Study to Evaluate STK-012 as a Single Agent and in Combination Therapy in Subjects With Front-line Advanced NSCLC and Other Selected Indications

NCT ID: NCT05098132Sponsor: SynthekineLast updated: 2026-03-18

Summary

This is a phase 1/2, multicenter, open-label study. The phase 1 portion is a dose escalation and expansion study of STK-012 as monotherapy and in combination therapy in patients with selected advanced solid tumors. The phase 2 portion is a randomized study of STK-012 in combination with standard of care (SoC) pembrolizumab, pemetrexed, and carboplatin versus SoC, in patients with first line, PD-L1 negative, non-squamous, non-small cell lung cancer.

Detailed description

Phase 1 \[closed to enrollment\]: The phase 1a portion is a dose escalation study to evaluate STK-012 as monotherapy and in combination therapy in patients with selected solid tumors. The phase 1b portion is a dose expansion study to evaluate STK-012 as monotherapy and in combination therapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types. Phase 2 \[open to enrollment\]: The phase 2 portion is a randomized, open label study to evaluate STK-012 at two dose levels in combination with standard of care (SoC) pembrolizumab, pemetrexed and carboplatin, versus SoC, in patients with first line, PD-L1 negative, non-squamous, non-small cell lung cancer.

Arms & interventions

  • DrugSTK-012

    Engineered Interleukin-2 (IL-2) selective for antigen activated T cells

  • Drugpembrolizumab

    anti-PD-1 monoclonal antibody

  • Drugpemetrexed

    chemotherapy

  • Drugcarboplatin

    chemotherapy

Outcome measures

Primary

  • Phase 1a: Treatment emergent adverse events (TEAEs)

    Incidence of TEAEs in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 1a: Serious adverse events (SAEs)

    Incidence of SAEs in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 1a: Dose limiting toxicities (DLTs)

    Incidence of DLTs in participants with select advanced solid tumors

    Time frame: Cycle 1, Days 1 through 21

  • Phase 1a: Deaths

    Incidence of death in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment until death, up to 4 years

  • Phase 1b: TEAEs at the RP2D

    Incidence of TEAEs at the recommended phase 2 dose (RP2D) in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 1b: SAEs at the RP2D

    Incidence of SAEs at the RP2D in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 1b: Deaths at the RP2D

    Incidence of death at the RP2D in participants with select advanced solid tumors

    Time frame: From 1st dose of study treatment until death, up to 4 years

  • Phase 2: Overall response rate (ORR) in Arm A versus Arm C

    To compare the ORR in 1L PD-L1 negative NSQ NSCLC subjects treated with STK-012 2.25 mg + SoC vs. SoC (Arms A vs. C). ORR is the proportion of subjects with confirmed complete response (CR) or confirmed partial response (PR) per BICR.

    Time frame: From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years

Secondary

  • Phase 1: ORR

    Time frame: From enrollment until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years

  • Phase 1: Progression free survival (PFS)

    Time frame: From enrollment until first documentation of disease progression per investigator assessment or death due to any cause, whichever occurs first, up to 4 years

  • Phase 1: Overall survival (OS)

    Time frame: From enrollment until death due to any cause, up to 4 years

  • Phase 1/2: STK-012 ADAs

    Time frame: From screening through 30 days after last dose of STK-012

  • Phase 1/2: AUC of STK-012

    Time frame: From screening through 30 days after last dose of STK-012

  • Phase 1/2: Cmax of STK-012

    Time frame: From screening through 30 days after last dose of STK-012

  • Phase 1/2: Tmax of STK-012

    Time frame: From screening through 30 days after last dose of STK-012

  • Phase 1/2: Half life of STK-012

    Time frame: From screening through 30 days after last dose of STK-012

  • Phase 2: PFS in Arm A versus Arm C

    Time frame: From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years

  • Phase 2: ORR in Arm B versus Arm C

    Time frame: From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years

  • Phase 2: PFS in Arm B versus Arm C

    Time frame: From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years

  • Phase 2: OS in Arm A versus C

    Time frame: From randomization until death due to any cause, up to 4 years

  • Phase 2: OS in Arm B versus C

    Time frame: From randomization until death due to any cause, up to 4 years

  • Phase 2: TEAEs

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 2: SAEs

    Time frame: From 1st dose of study treatment through 90 days after last dose

  • Phase 2: Deaths

    Time frame: From 1st dose of study treatment until death, up to 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Selected Inclusion Criteria: 1. Phase 1 \[closed to enrollment\] 2. Phase 2 \[open to enrollment\]: * Diagnosis of non-small cell lung cancer (NSCLC). * Stage IV or Stage IIIB/IIIC and not a candidate for definitive treatment. * Non-squamous (NSQ) cell histology. * No prior systemic therapy for advanced/metastatic NSQ NSCLC. * Tumor is PD-L1 negative (TPS \<1%) by local testing. * No known actionable EGFR, ALK, ROS1, or other actionable genomic aberrations for which there is a local standard of care available as front line therapy. Selected Exclusion Criteria: 1. Phase 1 \[closed to enrollment\] 2. Phase 2 \[open to enrollment\]: * Prior immune checkpoint inhibitor (anti-PD\[L\]1 and/or anti-CTLA-4) treatment * Tumor with small cell, neuroendocrine, or sarcomatoid components. * Received radiotherapy ≤ 7 days of the first dose of study treatment. * Known untreated central nervous system metastases * Any history of carcinomatous meningitis

Study locations (27)

University of Arizona Cancer Center

Tucson, Arizona, 85721

Recruiting
Mikayla Kirby · Contact

Beverly Hills Cancer Center

Beverly Hills, California, 90211

Recruiting
Ali Muhammad · Contact

Providence Medical Foundation

Fullerton, California, 92835

Recruiting
Linda Gozar · Contact

UC San Diego Moores Cancer Center

La Jolla, California, 92093-0698

Active Not Recruiting

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663

Recruiting
Ariel Klingfus · Contact
Holland Orndorff · Contact

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404

Recruiting

Yale New Haven Hospital, Yale Cancer Center

New Haven, Connecticut, 06510

Recruiting
Jialing Zhang, PhD · Contact

Georgetown University

Washington D.C., District of Columbia, 20057

Recruiting

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Justin Gainor, MD · Contact

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
Alexandra Childs, NP · Contact

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

HealthPartners Cancer Center at Regions Hospital

Saint Paul, Minnesota, 55101

Recruiting

Northwell Health

Lake Success, New York, 11042

Recruiting
Northwell Cancer Trials · Contact

NYU Langone Health

New York, New York, 10016

Recruiting
Salman Punekar, MD · Contact
Joshua Sabari, MD · Contact

Columbia University Irving Medical Center

New York, New York, 10032

Active Not Recruiting

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065

Recruiting
Adam Schoenfeld, MD · Contact

Duke Cancer Center

Durham, North Carolina, 27710

Recruiting

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210

Recruiting
Danny Lawson · Contact
Kai He, MD · Contact

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Active Not Recruiting

Baptist Memorial Hospital Cancer Center

Memphis, Tennessee, 38120

Recruiting

Sarah Cannon Research Institute - Nashville

Nashville, Tennessee, 37203

Active Not Recruiting

Renovatio Clinical

El Paso, Texas, 79915

Withdrawn

Oncology Consultants

Houston, Texas, 77303

Recruiting
Julio Peguero, MD · Contact

Renovatio Clinical

The Woodlands, Texas, 77380

Withdrawn

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting
Blake Patterson · Contact

Northwest Medical Specialties

Tacoma, Washington, 98405

Recruiting
CarrieAnn Brown · Contact
Kiersten Peart · Contact