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

Study Identifier:
STK-012-101
CT.gov Identifier:
NCT05098132
EudraCT Identifier:
202552263214
EU Trial (CTIS) Number:
2025-522632-14-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

To assess the safety, efficacy and PK of STK-012 as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors. To evaluate the safety, pharmacokinetics, immunogenicity, preliminary efficacy, and pharmacodynamics of STK-012 as monotherapy and in combination with pembrolizumab. Phase Ib: to evaluate STK-012 as monotherapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types, including renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). Longitudinal blood samples at pretreatment, peak (Day8) and trough (Day21) of dosing cycles 1–3 were analyzed for STK-012 pharmacokinetics (PK), cytokines, and effects on immune cells. T-cell clonality was analyzed by TCR- sequencing pre/post a single dose of STK-012 (quantifying >10-fold expanding clones).

To investigate the safety and efficacy of STK-012 in combination with standard dose pembrolizumab and chemotherapy vs. the safety and efficacy of standard dose pembrolizumab and chemotherapy in patients with first-line, PD-L1 negative NSQ NSCLC.

To evaluate the safety, pharmacokinetics, immunogenicity, pharmacodynamics, and antitumor activity of STK-012 as monotherapy and in combination in subjects with advanced solid tumors

Main objective (English)

To compare the ORR in 1L NSQ NSCLC (PD L1<1% or STK11m) subjects treated with STK 012 2.25 mg + PCT vs. PCT (Arms A vs. C)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Ovarian
Solid Tumor
Metastatic Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Selected Inclusion Criteria:
  • Phase 1: Selected advanced solid tumors
  • Phase 2:
  • 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.
  • Must have a tumor that meets at least one of the following criteria on local testing:
  • PD-L1 negative (TPS <1%), OR;
  • STK11 mutated on tumor tissue or ctDNA
  • 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.
  • as per ctis:
  • 01. Provide written informed consent to participate in the study and follow the study procedures.
  • 04. Subjects must have measurable disease by RECIST 1.1 as assessed by the local site investigator or radiology department. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • 05. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 28 days before randomization for Phase 2
  • 06. Adequate organ function within 28 days before randomization for Phase 2, as defined by the protocol
  • 07. Female subjects of childbearing potential must agree to use a highly effective method of birth control, as defined by the protocol.
  • 08. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours of the first dose of study treatment.
  • 09. Male subjects with female partners of childbearing potential must agree to use highly effective methods of birth control, as defined by the protocol, or a male condom plus spermicide and must refrain from donating sperm during the treatment period and for 180 days after the last dose of study treatment.
  • 10. Female partners (of childbearing potential) of male subjects must also use a highly effective method of birth control, as defined by protocol, during the treatment period and for 180 days after the last dose of study treatment, if the male subject’s only birth control method is male condom plus spermicide.
  • 17. Subjects who received adjuvant, neoadjuvant or consolidation chemotherapy are eligible if the therapy was completed >6 months prior to initiation of study treatment. Subjects must not have received any prior adjuvant, neoadjuvant or consolidation ICI therapy.
  • 11. Subjects are able and willing to complete the entire study according to the applicable study schedule of assessments.
  • 12. Subjects must have histologically or cytologically confirmed diagnosis of stage IV (M1a, M1b or M1c per AJCC 8th edition) or stage IIIB/IIIC (N2 or N3 per AJCC 8th edition) NSQ NSCLC if they are not candidates for definitive treatment.
  • 13. Subject’s tumor must have predominantly non-squamous cell histology NSCLC. Subject’s tumor must not have rare subtypes (mucinous histology or tumors with small cell, neuroendocrine or sarcomatoid components).
  • 14. No known AGAs by tumor or ctDNA testing in EGFR, ALK, or ROS1 or other AGAs for which there is a local SoC available as 1L therapy.
  • 15. Subjects must have a tumor that is negative for PD-L1 (TPS <1%) per local assessment
  • 16. Subjects must not have received prior systemic treatment for their advanced NSQ NSCLC.
  • 02. Male and female subjects age ≥18 years on day of signing ICF.
  • 03. Life expectancy >3 months as determined by the investigator.
  • 18. Subjects must have a tumor that meets at least one of the following criteria on local testing in a CLIA certified or equivalent setting: Negative for PD-L1 (TPS <1%) OR STK11 mutated on tumor tissue or ctDNA.
  • 19. Subjects enrolled must provide an archival tumor sample collected within 24 months of screening, if available.
Exclusion criteria
  • Selected Exclusion Criteria:
  • 2. Phase 2:
  • Prior immune checkpoint inhibitor (anti-PD[L]1 and/or anti-CTLA-4) treatment
  • Rare tumor subtypes (mucinous histology or tumors with small cell, neuroendocrine, or sarcomatoid components).
  • Received radiotherapy ≤ 7 days of the first dose of study treatment.
  • Known active central nervous system metastases
  • Any history of carcinomatous meningitis
  • as per ctis:
  • 01. 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.
  • 10. Known active or history of autoimmune disease or a syndrome that requires steroids or immunosuppressive agents. Subjects are permitted to enroll if they have vitiligo, type 1 diabetes mellitus, resolved childhood asthma; residual hypo- or hyperthyroidism due to an autoimmune condition not requiring immunosuppressive treatment; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).
  • 11. Diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Exceptions include inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted.
  • 12. History of allogeneic tissue/solid organ transplant.
  • 13. Clinically significant (ie. active) cardiovascular disease or risk factors at screening, as defined by the protocol.
  • 14. History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than their primary malignancy, that in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluations, procedures, or completion.
  • 15. Subjects with uncontrolled intercurrent illnesses, including immune colitis, interstitial lung disease, or a history of immune pneumonitis or pulmonary fibrosis that required oral or intravenous glucocorticoids.
  • 16. Evidence of any serious active bacterial, viral, parasitic, or systemic fungal infections requiring systemic therapy within the 30 days prior to the first dose of study drug.
  • 17. Known additional malignancy that is progressing or has required active treatment within the past 2 years. Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma and CC in situ), excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Subjects with low-risk early-stage prostate cancer (T1 T2a, Gleason score ≤6, and PSA ≤10ng/ml) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
  • 18. Receipt of a live-virus vaccine within 30 days prior to first dose of study drug and while on study (seasonal flu vaccines and coronavirus disease 2019 [COVID-19] vaccines that do not contain live-virus are permitted).
  • 19. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • 02. Received radiotherapy ≤ 7 days prior to the 1st dose of study treatmen
  • 20. HIV infection confirmed during the Screening Period by a positive serum HIV test.
  • 21. Active hepatitis B virus infection or hepatitis C virus (HCV) infection confirmed during the Screening Period by a positive hepatitis B surface antigen or positive anti-hepatitis C virus antibody (anti-HCV) test. Exceptions include subjects with a reactive or indeterminate/equivocal anti-HCV test with a negative HCV RNA test.
  • 22. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, defined as starting with the screening visit through 180 days after the last dose of study treatment.
  • 03. Received prior IL-2-based or IL-15-based cytokine therapy.
  • 09. Severe hypersensitivity (NCI CTCAE Grade ≥3) to monoclonal antibodies, including pembrolizumab and/or any of its excipients.
  • 23. Prior use of an anti-PD(L)1 agent or an agent directed to another stimulatory or co inhibitory receptors (eg., CTLA4, OX40, CD137) is exclusionary for enrollment into Part G.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Dublin
Dublin, Ireland, D07 R2WY
Investigator
Austin Duffy
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer
Ovarian
Solid Tumor
Metastatic Cancer
Location
START La Rioja
Logroño, La Rioja, Spain, 26006
Investigator
Maria de Miguel
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer
Ovarian
Solid Tumor
Metastatic Cancer