Phase 2 Study of Fingolimod in Lung Cancers

Inclusion criteria

• Voluntary, signed, and dated, Institutional Review Board (IRB) approved consent form in accordance with regulatory and institutional guidelines.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female
• 18 years of age or older
• Measurable/evaluable as defined by RECIST 1.1 at baseline of advanced/metastatic non-small cell lung cancer progressed on 2L+ systemic therapy with any molecular subtype and PD-L1 Tumor Proportion Score (TPS).
• Measurable/evaluable as defined by RECIST 1.1 at baseline of extensive stage small cell lung cancer progressed on 2L+ systemic therapy.
• Ability to take oral medication and be willing to adhere to the fingolimod regimen.
• ECOG performance status 0-2
• Baseline lymphocyte count \>1000 cells/mL
• For females of reproductive potential: use of highly effective contraception for at least 1 month before screening and agreement to use such a method during study participation and for an additional 2 months after the end of fingolimod administration.
• For males of reproductive potential: use of condoms or other methods during and for an additional 2 months after the end of fingolimod treatment to ensure effective contraception with a partner.

Exclusion criteria

• Patients who have had a recent (within the last 6 months) occurrence of cardiac event including myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or New York Heart Association Class III or IV heart failure, and congenital long QT-syndrome
• Patients who are receiving any medication(s) identified as having a Category D or higher interaction with the identified study agent who cannot be switched to another agent or discontinued before treatment if clinically appropriate. This medication review will be conducted by an oncology-trained Doctor of Pharmacy and discussed with the investigators before starting the treatment phase of this study. Careful evaluation for the following class of medications should be warranted due to their potential for severe side effects:
• Concurrent therapy with QT-prolonging medications with a known risk of torsade de pointes
• Concurrent therapy with drugs that slow heart rate or atrioventricular conduction
• Concurrent therapy with antineoplastic, immunosuppressive, or immune-modulating therapies
• Patients taking ketoconazole who have not completed their last dose at least 2 weeks before starting fingolimod.
• Active untreated brain metastases. Patients are eligible if brain metastases are previously treated and are asymptomatic. Patients must be neurologically stable and must be on stable or tapering corticosteroids 2 weeks before Cycle 1 Day 1
• Patients who have a history or presence of Mobitz Type II 2nd-degree or 3rd-degree atrioventricular block or sick sinus syndrome, unless patients have a functioning pacemaker.
• Patients who have a baseline QTc interval ≥ 500 msec
• Patients who have cardiac arrhythmias requiring Class IA or Class III anti-arrhythmic drugs.
• Class IA: disopyramide (Norpace), quinidine (Quinidex), procainamide (Procanbid)
• Class III: dronedarone (Multaq), dofetilide (Tikosyn), sotalol (Betapace), ibutilide (Corvert), amiodarone (Nexterone)
• Patients who have a hypersensitivity or allergic reaction (including rash, urticaria, and angioedema) to fingolimod or any of the excipients.
• Patients who have an active, uncontrolled acute or chronic bacterial, viral, or fungal infection
• Patients who have not completed all immunizations in accordance with current immunization guidelines before initiating fingolimod therapy
• Unwillingness or inability to comply with procedures required in this protocol.
• Patients who are currently participating in any other clinical trial of an investigational product
• Female patients who are of child-bearing potential (WOCBP) who are pregnant, planning to become pregnant during the study, or lactating. A urine pregnancy test for WOCBP will be collected during the screening period. Females will be determined to be not of child-bearing potential with a history of hysterectomy, tubal ligation, or age 45 or older with postmenopausal status \> 12 months.