Durvalumab and Lurbinectedin for the Treatment of Relapsed or Refractory Small Cell Lung Cancer

Inclusion Criteria:

• Age >= 18 years

• Histological or cytological confirmation of small cell lung cancer

• Prior treatment requirements:

• Relapsed or progressed after only one prior chemotherapy and PD-1 or PD-L1inhibitor regimen

• Prior therapy must have been an etoposide platinum doublet combined with PD-1or PD-L1 inhibitor

• Group 1: Must have "platinum-sensitive" disease according to the followingdefinitions:

• "Sensitive" disease: Relapse occurred > 90 days after completion of priortherapy

• "Resistant" Disease: Relapse occurred =< 90 days after completion of priortherapy

• Group 2: May have "platinum-sensitive" (Group 2A) or "platinumresistant" (Group 2B) disease

• Measurable disease

• Body weight > 30 kg

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

• Hemoglobin >= 9.0 g/dL (obtained =< 15 days prior to registration)

• Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 15 days prior toregistration)

• Platelet count >= 100,000/mm^3 (obtained =< 15 days prior to registration)

• Albumin >= 2.5 mg/dL (obtained =< 15 days prior to registration)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN iftotal bilirubin is > 1.5 x ULN (obtained =< 15 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 xULN for patients with liver involvement) (obtained =< 15 days prior to registration)

• Creatinine OR glomerular filtration rate (GFR) =< 1.5 x ULN OR glomerular filtrationrate (GFR) > 60 mL/min for patients with creatinine > 1.5 x ULN (obtained =< 15 daysprior to registration)

• Negative pregnancy test done =< 7 days prior to registration, for persons ofchildbearing potential only

• Persons able to become pregnant OR able to father a child must be willing to use anadequate method of contraception while on treatment and for 120 days after lasttreatment

• Life expectancy >= 12 weeks

• Provide written informed consent

• Willingness to provide mandatory blood specimens for correlative research

• Willingness to provide mandatory tissue specimens for correlative research

• Willing to return to Mayo Clinic for follow-up (during the active monitoring phaseof the study)

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whosegenotoxic, mutagenic and teratogenic effects on the developing fetus and newborn areunknown:

• Pregnant persons

• Nursing persons

• Persons of childbearing potential OR able to father a child who are unwillingto employ adequate contraception

• Any of the following prior therapies:

• Live vaccine < 30 days prior to registration, including intranasal flu vaccine (e.g. Flu-Mist[R]) (Note: Injected seasonal influenza vaccine is not "live")

• Surgery < 28 days prior to registration

• Chemotherapy or targeted small molecule therapy < 21 days prior to registration

• Radiation therapy < 21 days prior to registration

• Investigational therapy or investigational device < 14 days prior toregistration

• Failure to recover to =< grade 1 (or baseline) from adverse events due to previouslyadministered therapies or prior surgery. Exceptions: Neuropathy, fatigue, and/oralopecia may be grade 1

• Known active central nervous system (CNS) metastases. NOTE: Patients with previouslytreated brain metastases may participate provided all of the following are true:

• They are stable (without evidence of progression by imaging =< 4 weeks prior toregistration and any neurologic symptoms have returned to baseline)

• Have no evidence of new or enlarging brain metastases, and

• Are not using steroids =< 14 days prior to registration

• Known leptomeningeal disease

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens

• Known active human immunodeficiency virus (HIV) infection (defined as patients whoare not on anti-retroviral treatment and have detectable viral load and CD4+ < 500/ml). NOTE: HIV-positive patients who are well controlled on anti-retroviraltherapy are allowed to enroll

• Active autoimmune disease requiring systemic treatment, documented history of severeautoimmune disease, or a syndrome that requires systemic steroids orimmunosuppressive agents. NOTE: Exceptions are allowed for:

• Vitiligo

• Resolved childhood asthma/atopy

• Intermittent use of bronchodilators or inhaled steroids

• Daily steroids at dose of =< 10mg of prednisone (or equivalent)

• Local steroid injections

• Stable hypothyroidism on replacement therapy

• Stable diabetes mellitus on non-insulin therapy

• Sjogren's syndrome

• Current or prior use of immunosuppressive medication < 14 days prior toregistration. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,intraarticular injection)

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or its equivalent

• Steroids as premedication for hypersensitivity reactions (e.g., premedicationfor computed tomography [CT] scans)

• Uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection requiring systemic therapy

• Interstitial lung disease

• Serious, chronic gastrointestinal conditions associated with diarrhea (e.g.,Crohn's disease or others)

• Known active hepatitis B (i.e., known positive hepatitis B virus [HBV] surfaceantigen [HBsAg] reactive)

• Known active hepatitis C (i.e., positive for hepatitis C virus ribonucleic acid [HCV RNA] detected by polymerase chain reaction [PCR])

• Known active tuberculosis (TB)

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Unstable cardiac arrhythmia or

• Psychiatric illness/social situations that would limit compliance with studyrequirements (e.g., substance abuse)

• History of myocardial infarction =< 6 months, or congestive heart failure requiringuse of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• Receiving any other investigational agent which would be considered as a treatmentfor the primary neoplasm

• Hypersensitivity to durvalumab or any of its excipients

• Previous adverse event attributed to durvalumab or other PD-1 or PD-L1 directedtherapy that led to drug discontinuation

• History of grade >= 3 immune-related adverse event or any grade of immune-relatedneurologic or ocular adverse event while receiving immunotherapy. Note: Patients whohad endocrine adverse events =< grade 2 are allowed to enroll if they are stable onappropriate replacement therapy and asymptomatic

• Other active malignancy < 6 months prior to registration. EXCEPTIONS: Non-melanoticskin cancer, papillary thyroid cancer, or carcinoma-in-situ of the cervix, or otherscuratively treated and now considered to be at less than 30% risk of relapse