Study of STK-012 Alone and with Other Treatments in Patients with Advanced Lung Cancer and Other Cancers

Prior treatment

• 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.
• 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).
• Received radiotherapy ≤ 7 days prior to the 1st dose of study treatment.
• Received prior IL-2-based or IL-15-based cytokine therapy.
• History of idiopathic pulmonary fibrosis (including pneumonitis), non-infectious pneumonitis/ interstitial lung disease that required steroids, organizing pneumonia (ie, bronchiolitis obliterans and cryptogenic organizing pneumonia), or has current pneumonitis/interstitial lung disease.
  • 05.Currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anti-cancer treatment to Grade ≤2.
• Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 7 days prior to first dose of study treatment. Subjects with untreated brain metastases may be enrolled if they meet all of the following criteria: no lesion >0.5 cm, asymptomatic, no edema, and no steroid requirement.
• 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.
• 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.
• 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.
• 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.

Other illness

• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• 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.
• 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).
• Any history of carcinomatous meningitis.
• Severe hypersensitivity (NCI CTCAE Grade ≥3) to monoclonal antibodies, including pembrolizumab and/or any of its excipients.
• History of allogeneic tissue/solid organ transplant.
• Clinically significant (ie. active) cardiovascular disease or risk factors at screening, as defined by the protocol.
• 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.
• 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.

Lab values

• HIV infection confirmed during the Screening Period by a positive serum HIV test.

Other

• 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.

• Provide written informed consent to participate in the study and follow the study procedures.
• Subjects are able and willing to complete the entire study according to the applicable study schedule of assessments.
• 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.
• 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).
• 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.
• Subjects must have a tumor that is negative for PD-L1 (TPS <1%) per local assessment
• Subjects must not have received prior systemic treatment for their advanced NSQ NSCLC.
• Male and female subjects age ≥18 years on day of signing ICF.
• Life expectancy >3 months as determined by the investigator.
• 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.
• Subjects enrolled must provide an archival tumor sample collected within 24 months of screening, if available.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 28 days before randomization for Phase 2
• Adequate organ function within 28 days before randomization for Phase 2, as defined by the protocol
• Female subjects of childbearing potential must agree to use a highly effective method of birth control, as defined by the protocol.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours of the first dose of study treatment.
• 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.
• 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.
• 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.