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`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`Our STN: BL 103792/5150
`
`N-oV i 6 2006
`
`Genentech, Incorporated
`Attention: Todd W. Rich, M.D.
`Vice President, Clinical and Commercial Regulatory Affairs
`1 DNA Way, MS# 242
`South San Francisco, CA 94080-4990
`
`Dear Dr. Rich:
`
`Your request to supplement your biologics license application for Trastuzumab as par of a
`treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel, for the adjuvant
`patients with HER2-overexpressing, node-positive breast cancer, has been
`
`treatment of
`
`approved.
`
`administration, and new dosing regimens are required to contain an aSsessment of
`
`All applications for new active ingredients, new dosage forms, new indications, new routes of
`the safety and
`effectiveness of the product in pediatric patients unless this requirement is waived or deferred.
`Weare waiving the pediatric study requirement for this application.
`
`We acknowledge your written commitments to conduct postmarketing studies as described in
`November 2, 2006, as outlined below:
`
`your letter of
`
`Postmarketine Studies subject to reportine requirements of 21 CFR 601.70.
`
`1. To provide a final study report at the time of the final analysis of overall survival
`(analysis based on 710 deaths) in accordance with the statistical analysis plan of
`April 2005 for integrated analysis of Studies NSABP B31 and NCCTG N983 1. The final
`study report should include the primary datasets and programs for generation of analyses
`and all subset analyses for the final analysis of overall survival and an updated analysis of
`disease-free survival, including exploratory analyses in subgroups based on the timing
`hormonal treatment administered to patients. The 710th death is expected to
`occur by September 30,2011, and the final study report will be submitted by
`September 30, 2012.
`
`and type of
`
`IMMUNOGEN 2194, pg. 1
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`To provide final analysis of cardiac toxicity based on serial ejection fraction monitoring,
`characterizing the cumulative incidence, severity, duration and reversibility over the
`immediate post-treatment period (18 months from initiation of adjuvant chemotherapy) in
`all patients enrolled as of the termination of study enrollment in April 2005.
`The final study report should include the primary datasets and programs for generation of
`analyses; analyses will include, but not be limited to the analyses described in the
`statistical analysis plan of April 2005 for integrated analysis of Studies NSABP B31 and
`NCCTG N983l. The completion of this aspect of the integrated study (18 months from
`the April 2005 termination of accrual) is October 31, 2006, and the final study report will
`May 31,2008.
`
`be submitted by
`
`3. To provide interim cardiac safety updates on an annual basis beginning on
`September 30, 2006, as the first cut-off date and ending with a final comprehensive
`cardiac safety analysis report submitted by September 30,2012. Each annual cardiac
`safety update wil include a detailed narrative summary of each new clinical event with
`associated radiologic reports and laboratory findings for all patients enrolled as of the
`termination of study enrollment in April 2005 The first annual cardiac safety update wil
`28, 2007. The final comprehensive cardiac safety analysis will be
`included in the final study report based on 710 deaths. In addition, the final
`comprehensive study report will contain primary datasets for the ITT population and
`summary analyses that include, but are not limited to, the analyses described in the
`statistical analysis plan of April 2005 for integrated analysis of Studies NSABP B31 and
`NCCTG N9831.
`
`be submitted by April
`
`4. To provide a final study report characterizing the safety profie of
`
`patients who received at least one dose of
`
`protocol-prescribed therapy as of
`
`the two studies among
`the
`termination of study enrollment in April 2005. The study report wil contain primary
`datasets that include final study data for all patients who received at least one dose of
`protocol-specified treatment and summary analyses that include, but are not limited to,
`the analyses described the statistical analysis plan of April 2005 for integrated analysis of
`Studies NSABP B31 and NCCTG N9831 The datasets should include study drug
`information sufficient to characterize exposure in each patient for the individual study
`drug components, including dose modification (reduction or suspension of dosing) and
`should provide the timing of the events in relation to specific study drug treatment. The
`database should also contain a flag to distinguish those patients who were included in the
`joint analysis ITT population in the original database from those patients who were not
`the integrated study (18
`months from the April 2005 termination of accrual) is September 30, 2006, and the final
`study report will be submitted by May 31, 2008.
`
`included in this population. The completion of
`
`this aspect of
`
`IMMUNOGEN 2194, pg. 2
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`Page 3 - BL 103792/5150
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`We request that you submit clinical protocols to your IN, with a cross-reference letter to this
`biologics license application (BLA), STN BL 103792. Submit non-clinical and chemistry,
`manufacturing, and controls protocols and all study final reports to your BLA STN BL 103792.
`Please use the following designators to label prominently all submissions, including
`supplements, relating to these postmarketing study commitments as appropriate:
`
`. Postmarketing Study Protocol
`. Postmarketing Study Final Report
`. Postmarketing Study Correspondence
`. Anual Report on Postmarketing Studies
`
`F or each postmarketing study subj ect to the reporting requirements of 2 1 CFR 601.70, you must
`describe the status in an annual report on postmarketing studies for this product. The status
`report for each study should include:
`
`information to identify and describe the postmarketing commitment,
`the original schedule for the commitment,
`the status of the commitment (i.e. pending, ongoing, delayed, terminated, or
`submitted),
`
`an explanation of
`
`the status including, for clinical studies, the patient accrual rate
`(i.e. number enrolled to date and the total planned enrollment), and
`a revised schedule if the study schedule has changed and an explanation of the
`basis for the revision.
`
`... .
`
`.
`
`As described in 21 CFR 601. 70( e), we may publicly disclose information regarding these
`postmarketing studies on our Web site (http://ww.fda.gov/cder/pmc/default.htm). Please refer
`to the February 2006 Guidance for Industry: Reports on the Status ofPostmarketing Studies-
`Implementation of Section 130 ofthe Food and Drug Administration Modernization Act of 1997
`(see http://ww.fda.gov/cber/gdlns/post130.htm) for further information.
`
`Please submit all final printed labeling at the time of use and include implementation information
`on FDA Form 356h. The final printed labeling (FPL) must be identical to the enclosed labeling
`(text for the package insert) submitted November 8, 2006. Marketing product with FPL that is
`not identical to the approved labeling text may render the product misbranded and an unapproved
`new drug. Please provide a PDF-format electronic copy as well as original paper copies (ten for
`circulars and five for other labels).
`
`promotional
`
`Administration, Center for Drug Evaluation and Research, Division of
`
`In addition, you may wish to submit draft copies of the proposed introductory advertising and
`labeling with a cover letter requesting advisory comments to the Food and Drug
`Drug Marketing,
`Advertising and Communication, 5901-B Ammendale Road, Beltsville, MD 20705-1266. Final
`initial
`
`'printed advertising and promotionallabeling should be submitted at the time of
`
`dissemination, accompanied by a FDA Form 2253.
`
`IMMUNOGEN 2194, pg. 3
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`Please submit within 30 days content of
`
`labeling (21 CFR 601.
`
`14(b)) in structured product
`labeling (SPL) format, as described at http://ww.fda.gov/oc/datacouncil/spl.htmL that is
`identical in content to the enclosed labeling text dated November 8, 2006. Upon receipt and
`Medicine for posting on the
`
`verification, we will transmit that version to the National Library of
`
`DailyMed website.
`
`All promotional claims must be consistent with and not contrary to approved labeling. You
`should not make a comparative promotional claim or claim of superiority over other products
`unless you have substantial evidence to support that claim.
`
`This information wil be included in your biologics license application file.
`
`Sincerely,
`
`r2~ kL
`
`Patricia Keegan, M.D.
`Director
`Division of Biologic Oncology Products
`Offce of Oncology Drug Products
`Center for Drug Evaluation and Research
`
`c.,¡;
`
`Enclosure: Final Printed Labeling
`
`IMMUNOGEN 2194, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`