Lorlatinib in ALK Inhibitor Treated Unresectable Advanced/Recurrent ALK-Positive Non Small Cell Lung Cancer Patients in India

Exclusion Criteria

• •1. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study enrollment. Palliative radiation (\<10 fractions) must have been completed at least 48 hours prior to study enrollment. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study enrollment. Whole brain radiation must have completed at least 4 weeks prior to study enrollment. Prior irradiation to \>25% of the bone marrow.
• •2. Major surgery within 4 weeks prior to enrollment. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
• •3. Known prior or suspected severe hypersensitivity to study drug or any component in its formulation.
• •4. Active and clinically significant bacterial, fungal, or viral infection.
• •5. Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions (active or within 3 months prior to enrollment), which may include, but are not limited to:
• •1. Arterial disease such as cerebral vascular accident/stroke (including transient ischemic attack \[TIA\]), myocardial infarction, unstable angina;
• •2. Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism;
• •3. Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class ≥II), second degree or third degree atrioventricular (AV) block (unless paced) or any AV block with PR interval \>220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 beats per minute (bpm) (unless participant is otherwise healthy such as long distance runners, etc.), machine read ECG with QT interval corrected for heart rate (QTc) \>470 msec, or congenital long QT syndrome.
• •6. History or known presence of interstitial fibrosis, interstitial lung disease (ILD), pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis.
• •7. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for enrollment in this study.
• •8. Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, ductal carcinoma in situ \[DCIS\] of the breast or localized and presumed cured prostate cancer) within the last 3 years prior to enrollment.
• •9. Concurrent use of any of the following food or drugs (consult the Sponsor if in doubt whether a food or a drug falls into any of the categories described below) within 12 days prior to the first dose of lorlatinib:
• •1. Known strong cytochrome (CYP)3A inducers (eg, carbamazepine, enzalutamide, mitotane, rifampin, St. John's Wort).
• •2. Known strong CYP3A inhibitors (eg, grapefruit juice or grapefruit/grapefruit related citrus fruits \[eg, Seville oranges, pomelos\], boceprevir, cobicistat, clarithromycin, conivaptan, diltiazem, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nelfinavir, paritaprevir, posaconazole, ritonavir alone and with elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir and voriconazole). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
• •3. Known CYP3A substrates with narrow therapeutic index, such as pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine).
• •4. Known permeability glycoprotein (P-gp) substrates with a narrow therapeutic index (eg, digoxin).
• •10. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are Pfizer employees directly involved in the conduct of the study.
• •11. Participation in other studies involving investigational drug(s) (Phases 1-4) during study participation.
• •12. Breastfeeding female participants.