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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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`Silver Spring MD 20993
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` NDA 202570/S-6
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`SUPPLEMENT APPROVAL
`RELEASE FROM POSTMARKETING REQUIREMENT
`FULFILLMENT OF POSTMARKETING
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`REQUIREMENTS/COMMITMENT
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`PF PRISM C.V.
`
` Attention: Mindy S. Meader
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` Associate Director, Worldwide Regulatory Strategy
`
` Pfizer Inc.
`10646 Science Center Drive
`San Diego, CA 92121
`
`
`Dear Ms. Meader:
`
`Please refer to your Supplemental New Drug Application (sNDA) received February 28, 2013,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Xalkori (crizotinib) capsules, 200mg, 250 mg.
`
`We acknowledge receipt of your amendments submitted on March 14, March 27, April 8, April
`10, April 18, April 23, May 15, May 28, June 5, June 10, June 21, June 24, August 2, August 21,
`September 11, September 30, October 8, October 9, October 10, October 24, October 28,
`November 6, November 13, November 14 and November 20, 2013.
`
`This Prior Approval Supplemental New Drug Application provides for inclusion in product
`labeling of the efficacy, clinical pharmacology, and adverse reaction data from Study A8081007
`and the clinical pharmacology study results on the effect of gastric pH elevating agents on
`crizotinib pharmacokinetics.
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`APPROVAL & LABELING
`
`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`CONTENT OF LABELING
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`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`Reference ID: 3410361
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`

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`NDA 202570/S-6
`Page 2
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`of labeling must be identical to the enclosed labeling (package insert and patient information)
`with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`Also within 14 days, amend all pending supplemental applications that includes labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`SUBPART H FULFILLED
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`We approved this NDA under the regulations at 21 CFR 314 Subpart H for accelerated approval
`of new drugs for serious or life-threatening illnesses. Approval of this supplement fulfills the
`below postmarketing requirement (PMR) made under 21 CFR 314.510.
`
`1789-1
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`Clinical trial report and datasets from A8081007: Phase 3, Randomized, Open-
`label Study of the Efficacy and Safety of PF-02341066 vs. Standard of Care
`(Pemetrexed or Docetaxel) in Patients with Advanced Non-Small Cell Lung
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`Cancer Harboring a Translocation or Inversion Event Involving the Anaplastic
`Lymphoma Kinase Gene Locus.
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`RELEASE FROM POSTMARKETING REQUIREMENT
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`Since we have determined that the data provided in this supplement verify that clinical benefit is
` conferred by XALKORI (crizotinib) capsules, you are released from PMR 1789-2, also required
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`under 21 CFR 314.510.
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`1789-2
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`Clinical trial report and datasets from A8081014: Phase 3, Randomized, Open-
`label Study of the Efficacy and Safety of Crizotinib vs. Pemetrexed/Cisplatin or
`Pemetrexed/Carboplatin in Previously Untreated Patients with Non-Squamous
`Carcinoma of the Lung Harboring a Translocation or Inversion Event Involving
`the Anaplastic Lymphoma Kinase Gene Locus.
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`
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`Reference ID: 3410361
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`

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`NDA 202570/S-6
`Page 3
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` REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are exempt
`from this requirement.
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`FULFILLMENT OF POSTMARKETING REQUIREMENT
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`This supplement contains your PMR final trial report for the following PMR listed in the August
`26, 2011 approval letter.
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`1789-10
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`Conduct a trial in humans to determine how to dose crizotinib with regard to
`gastric pH elevating agents (i.e., a proton-pump inhibitor, an H2-receptor
`antagonist, and an antacid).
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`We have reviewed your final trial report and conclude that the above requirement is fulfilled.
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`FULFILLMENT OF POSTMARKETING COMMITMENT
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`This supplement contains your postmarketing commitment (PMC) final trial report for the
`following PMC listed in the August 26, 2011 approval letter.
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`1789-12
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`To conduct exposure-response analysis for progression-free survival, response
`rate, overall survival and safety endpoints utilizing data from confirmatory trial
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`A8081007 and to submit the analysis plan for review.
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`
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`We have reviewed your final trial report and conclude that the above commitment is fulfilled.
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`We remind you that there are postmarketing requirements and postmarketing commitments listed
`in the August 26, 2011 approval letter that are still open.
`
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
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`We remind you of your postmarketing commitments:
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`2100-1
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`To submit the final trial report for Study A8081007 that includes the final analysis
`of overall survival as specified in the version of Study A8081007 submitted on
`February 5, 2013, in order to characterize the effects of Xalkori (crizotinib)
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`treatment on overall survival.
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`Reference ID: 3410361
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`

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`NDA 202570/S-6
`Page 4
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`The timetable you submitted on November 14, 2013, states that you will conduct
`this trial according to the following schedule:
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`Trial Completion (Final OS Analysis) Date: June 2015
`Final Report Submission: September 2016
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`Clinical trial report and datasets from A8081014: Phase 3, Randomized, Open-label
`Study of the Efficacy and Safety of Crizotinib vs. Pemetrexed/Cisplatin or
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`Pemetrexed/Carboplatin in Previously Untreated Patients with Non-Squamous
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`Carcinoma of the Lung Harboring a Translocation or Inversion Event Involving the
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`Anaplastic Lymphoma Kinase Gene Locus.
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`The timetable you submitted on November 13, 2013, states that you will conduct
`this trial according to the original schedule outlined in our August 26, 2011
`approval letter:
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`Trial Completion Date: December 2015
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`Final Report Submission: June 2016
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`
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`Submit clinical protocols to your IND 73544 for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all postmarketing final reports to this NDA. In
`addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a status
`summary of each commitment in your annual report to this NDA. The status summary should
`include expected summary completion and final report submission dates, any changes in plans
`since the last annual report, and, for clinical studies/trials, number of patients entered into each
`study/trial. All submissions, including supplements, relating to these postmarketing
`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
`Correspondence.”
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`2100-2
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`Reference ID: 3410361
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`

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`NDA 202570/S-6
`Page 5
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` PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Mona Patel, Pharm.D., Regulatory Project Manager, at (301) 796-
`4236.
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`Sincerely,
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`{See appended electronic signature page}
`
`
`Patricia Keegan, M.D.
`Director
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`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3410361
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`PATRICIA KEEGAN
`11/20/2013
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`Reference ID: 3410361
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