A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC

• Drug: Lorlatinib
  ALK-positive NSCL treatment
  Other Name: PF-06463922
• Drug: Crizotinib
  ALK-positive NSCL treatment
  Other Name: Xalkori

• Experimental: Lorlatinib
  Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously
  Intervention: Drug: Lorlatinib
• Active Comparator: Crizotinib
  Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
  Intervention: Drug: Crizotinib

• Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.
• Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10.

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
• Availability of an archival FFPE tissue specimen.
• No prior systemic NSCLC treatment.
• ECOG PS 0, 1, or 2.
• Age ?18 years .
• Adequate Bone Marrow, Liver, Renal, Pancreatic Function
• Negative pregnancy test for females of childbearing potential

Exclusion Criteria:

• Spinal cord compression unless good pain control attained
• Major surgery within 4 weeks prior to randomization.
• Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization
• Active bacterial, fungal, or viral infection
• Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome
• Predisposing characteristics for acute pancreatitis in the last month prior to randomization.
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease
• Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization.

• Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib.

  1. known strong CYP3A inhibitors .
  2. known strong CYP3A inducers
  3. known P gp substrates with a narrow therapeutic index
• Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
• Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study.
• Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.