Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC

Exclusion Criteria

• •ALK or EGFR non-squamous non-small cell lung cancer.
• •Prior radiation therapy within 2 weeks prior to cycle one day one.
• •-Exception: Prior palliative radiotherapy is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected.
• •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• •-Note: Local surgery of isolated lesions for palliative intent is acceptable.
• •History of allogenic organ transplantation.
• •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,uveitis, etc\]). The following are exceptions to this criterion:
• •* Patients with vitiligo or alopecia
• •* Patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy)
• •* Any chronic skin condition that does not require systemic therapy
• •* Patients without active disease in the last 5 years may be included but only after consultation with the principal investigator
• •* Patients with celiac disease controlled by diet alone
• •Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids:
• •* Intranasal, inhaled, topical steroids, eye drops or local steroid injection (eg,intra-articular injection);
• •* Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent;
• •* Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication).
• •* Other immunosuppressive agents which, in the opinion of the investigator, are not expected to significantly impact study participation or the mechanism of action of the study therapy.
• •History of active primary immunodeficiency
• •Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration) or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms is allowed.
• •Uncontrolled CNS metastases; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicities have resolved to grade 1 or baseline and steroids are no longer required.
• •--Patients with asymptomatic brain metastasis are allowed if previous steroid treatment was discontinued for 5 half-lives.
• •History of leptomeningeal carcinomatosis
• •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 AEs or compromise the ability of the patient to give written informed consent
• •Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load 12 months, CD4+ count of ≥ 350 cells/uL, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 1 month on the same anti HIV medications.
• •Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB 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 RNA.
• •Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti HBcAb with detectable HBV DNA); AND
• •1. HCV positive (presence of anti-HCV antibodies); OR
• •2. HDV positive (presence of anti-HDV antibodies).
• •Vaccination with a live vaccine within 30 days of cycle one day one and while on trial is prohibited except for administration of inactivated vaccines.
• •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
• •Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies, cisplatin, other platinum-containing compounds, or mannitol. (NCI CTCAE v5.0 Grade ≥ 3).
• •Subjects taking prohibited medications as described in Section 6.5.2. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.
• •Participation in another clinical study with an investigational product during the last 2 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.