Durvalumab and Platinum Doublet Chemotherapy With or Without Abequolixron or Abequolixron Alone for the Treatment of Patients with Stage II-IIIA Non Small Cell Lung Cancer

Inclusion Criteria

• Willing and able to provide written informed consent obtained to participate in the study and Heath Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Age >= 18 years at the time of consent
• Histologically or cytologically confirmed non-small cell lung cancer for which surgical resection would be standard of care
• American Joint Commission on Cancer (AJCC) 8th edition stage II-IIIA confirmed squamous or non-squamous NSCLC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Body weight of > 40 kg
• Is able to swallow and retain oral medication
• Subjects must have a baseline oxygen (O2) saturation by pulse oximetry that is >= 90% both at rest and while walking, off supplemental oxygen
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Subjects must agree to not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or 90 days after receipt of the final dose of durvalumab
• Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• Life expectancy of at least 16 weeks
• No prior curative attempts for this cancer (i.e., surgery, radiation, systemic therapy) and not currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to the first dose of study intervention. No evidence of metastatic disease (M0)
• Hemoglobin (Hgb) >= 9 g/dL obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• White blood cell (WBC) >= 2 x 10^9/L obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Platelets >= 75 x 10^9/L obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Creatinine Clearance > 60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Bilirubin =< 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin < 3.0 mg/dL obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Aspartate aminotransferase (AST) =< 2.5 × ULN unless liver metastases are present, in which case it must be =< 5 x ULN obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Alanine aminotransferase (ALT) =< 2.5 × ULN unless liver metastases are present, in which case it must be =< 5 x ULN obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) =< 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants obtained within 72 hours prior to initiating study treatment *Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)
• Female subjects of childbearing potential: Female subjects of childbearing potential who are not totally sexually abstinent (i.e., refraining from heterosexual intercourse during the entire period of risk associated with study interventions) and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and continue to use it throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy). Non-sterilized male partners of a female subjects of childbearing potential must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female patients should also refrain from breastfeeding throughout this period
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 90 days after the last dose of study therapy

Exclusion Criteria

• Participation in another clinical study with an investigational product during the last 3 weeks
• Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment with the exception of those mentioned in this protocol. Concurrent use of hormonal therapy for noncancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Lack of full recovery from major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP
• History of allogenic organ transplantation
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the subject to give written informed consent
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis or non-autoimmune etiology], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: * Subjects with vitiligo or alopecia * Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Subjects without active disease in the last 5 years may be included but only after consultation with the study physician * Subjects with celiac disease controlled by diet alone
• The subject has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to study therapy administration. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Receipt of live attenuated vaccine (or any vaccines, with the exception of COVID-19 vaccinations and boosters) within 30 days prior to the first dose of study drugs. Note: Subjects, if enrolled, should not receive live vaccine while receiving study drugs and up to 30 days after the last dose of drugs
• Active systemic infection requiring therapy
• Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice)
• Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus ([HBV] surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• History of interstitial lung disease
• Subjects who require or may require pneumonectomy, as assessed by their surgeon, to obtain potentially curative resection of primary tumor
• Have clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study treatment, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication). Subjects are required to have a normal left ventricular ejection fraction as determined by either echocardiography. Subjects must have a Fridericia's corrected QT interval (QTcF) =< 470 msec
• Subject has grade >= 2 hypercholesterolemia (total cholesterol >300 mg/dL or 7.75 mmol/L) and/or hypertriglyceridemia (triglyceride >300 mg/dL or ≥ 3.42 mmol/L) in the fasting state
• Subject has a history of pancreatitis
• Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). Women should not breastfeed for at least 90 days after the last dose of durvalumab
• History of allergic reaction or hypersensitivity to the study drugs or any of their excipients
• Prior therapy with an anti-PD-1, anti-PD-L1, including durvalumab, or anti-CTLA-4 antibody (or any other antibody targeting T-cell co-regulatory pathways)
• Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy. * Subjects receiving medications that are metabolized by or inhibit CYP3A4, as well as those drugs for which OATP1B1 is the predominant uptake transporter, must have those medications discontinued prior to study treatment * Subjects requiring statin (e.g. rosuvastatin, atorvastatin, etc.) therapy. If subject is taking a statin but discontinuation is considered appropriate, the statin must be discontinued at least 5 days prior to starting study therapy