GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer

Inclusion criteria

• Age ≥ 18 years.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at the time of study treatment initiation.
• Have pathologically confirmed diagnosis of STK11 mutant NSCLC. STK11 mutation will be based on subject's local clinically accredited laboratory testing (Clinical Laboratory Improvement Amendments \[CLIA\]-certified) using deoxyribonucleic acid (DNA) sequencing test.
• Must have progressed on a pembrolizumab containing regimen and eligible for continuing pembrolizumab post-progression as determined by treating physician. Other anti-PD-1 or anti-PD-L1 checkpoint inhibitors may also be used in place of pembrolizumab
• Adequate bone marrow and organ function as defined by the following lab values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Platelets ≥ 100 x 10\^9/L.
• Hemoglobin ≥ 9 g/dL.
• Estimated glomerular filtration rate (GFR) (measured or calculated with Cockroft and Gault formula) \> 45mL/min.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present).
• Total bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3 x ULN with direct bilirubin within normal range.
• Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) (institutional limit).
• Patients must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
• Participant agrees to provide blood samples at the start of treatment and at multiple times during the study. Participant agrees to provide tumor biopsy tissue or have adequate archival formalin-fixed paraffin-embedded (FFPE) tissue available.

Exclusion criteria

• Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug.
• Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain metastasis. Subjects must have recovered from all radiation related toxicities.
• Active/untreated brain metastasis. Whole brain radiation or gamma knife radiosurgery performed less than 4 weeks prior to first administration of study drug. Previously treated brain metastasis allowed as long as not requiring steroids and stable on imaging at least 4 weeks after completing radiation therapy.
• Leptomeningeal involvement regardless of treatment status.
• Tumor with oncogenic mutation based on standard of care broad genomic profiling in EGFR, ALK, ROS1, RET, MET, or NTRK genes.
• History of autoimmune disorder, with exception of patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation who are eligible. Systemic use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks before the first administration of study drug.
• Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases, or who have not fully recovered from side effects of such treatment. Steroids for endocrine replacement or receipt of short-course of steroids during the preceding 4 week period as supportive medication such as for drug allergy, anti-emetic, etc. is allowed.
• Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.
• Has known immunosuppressive disease (e.g., HIV, AIDS or other immune depressing disease). Testing is not mandatory.
• Active, clinically serious infections or other serious uncontrolled medical conditions.
• Patient has known hypersensitivity to the components of the study drugs or any analogs.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
• Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease.
• History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline.
• Uncontrolled hypertension (systolic blood pressure \[SBP\] \> 160/diastolic blood pressure \[DBP\] \> 100 despite medical intervention).
• History of myocarditis of any etiology.
• History of ventricular arrhythmias.
• Patients diagnosed with an invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason ≤ 6 (under surveillance or treated), early-stage node-negative estrogen receptor positive (ER+)/progesterone receptor positive (PR+) breast cancer with Oncotype Dx score \< 25 not taking adjuvant hormonal therapy.
• Pregnant or nursing female participants.
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.
• Unwilling or unable to follow protocol requirements.