NSABP B-55/BIG Lynne Suhayda, RN, MSEd. Director, Clinical Coordinating Department. NRG Oncology - Pittsburgh, Pennsylvania

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1 NSABP B-55/BIG 6-13 Lynne Suhayda, RN, MSEd. Director, Clinical Coordinating Department NRG Oncology - Pittsburgh, Pennsylvania NRG Oncology Meeting July 15, 2016

2 Lynne Suhayda, RN, MSEd. No Financial Disclosures

3 NSABP B-55 A Randomised, Double-Blind, Parallel Group, Placebo-Controlled Multi-Centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients with Germline BRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy

4 NSABP B-55 Overview Adjuvant olaparib in TNBC patients with BRCA mutations at high risk of recurrence Post neoadjuvant BRCA TNBC, non-pathcr patients ER and/or PgR positive/her2 negative patients must have non-pathcr AND a CPS&EG score 3

5 NSABP B-55 Overview (Continued) Adjuvant olaparib in TNBC patients with BRCA mutations at high risk of recurrence Post adjuvant BRCA TNBC, patients with positive nodes and any tumor size or node negative and primary tumor is >2 cm Post adjuvant ER and/or PgR positive/her2 negative patients must have had 4 pathologically confirmed positive lymph nodes

6 NSABP B-55 Overview (Continued) Randomized to receive Olaparib 300 mg BID for 12 months or to receive placebo BID for 12 months. Patients are randomized ideally within 8 weeks but no longer than 12 weeks of their last treatment (surgery, chemotherapy or RT). Primary endpoint is invasive disease free survival (IDFS)

7 Genetic Selection Patient Eligibility Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious Patients who have a deleterious or suspected deleterious mutation based on local testing or central testing by Myriad are eligible. If there is a discrepancy between the local testing (positive) and Myriad (negative) the patient can participate in the study if the investigator believes it s appropriate. (gbrca expert advisory committee that investigators can consult with in these situations. Contact the Clinical Coordinating Dept.)

8 TNBC defined as: Major Eligibility Criteria ER and PgR negative-defined as IHC nuclear staining <1% (not eligible for endocrine therapy) HER2 negative defined as: - IHC 0, 1+ without ISH OR - IHC 2+ and ISH non-amplified with ratio <2.0 and if reported, average HER2 copy number <6 signals/cells OR - ISH non-amplified with ratio <2.0 and if reported, average HER2 copy number <6 signals/cells (without IHC)

9 Major Eligibility Criteria (Continued) ER and/or PgR Positive HER2 negative breast cancer ER and/or PR positive defined as IHC nuclear staining 1%. Any tumor locally assessed as either ER or PgR positive in either the core biopsy or the surgical specimen is considered positive.

10 Major Eligibility Criteria (Continued) Multifocal or multicentric invasive disease - lesions that were assessed for HER2 status were negative Synchronous bilateral invasive disease - lesions assessed for HER2 in both breasts were negative Lesion considered at highest risk for recurrence by the investigator is used to determine eligibility.

11 Major Eligibility Criteria (continued) Adjuvant Group Axillary Management Sentinel lymph node biopsy alone if negative or if only micrometastases ( 2.0 mm) OR If positive sentinel node biopsy then axillary nodal dissection or RT per local guidelines. Axillary dissection OR

12 Major Eligibility Criteria (continued) Axillary Management Neoadjuvant Group If sentinel node biopsy (SNB) before neoadjuvant chemotherapy: SNB alone if negative or if only micrometastases ( 2.0 mm) SNB positive - axillary node dissection or axillary nodal RT should follow completion of neoadjuvant chemotherapy

13 Major Eligibility Criteria (continued) Neoadjuvant Group Axillary Management If sentinel lymph node biopsy after neoadjuvant chemotherapy: - If SNB negative additional axillary surgery is not required. - SNB positive,micrometastases are regarded as positive - axillary surgery is required UNLESS the patient is in a clinical trial proposing radiotherapy as alternative treatment of axilla. Axillary dissection

14 Major Eligibility Criteria (continued) Patients have completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed. Systemic chemotherapy - completed at least 3 weeks prior to randomization. Adjuvant RT - completed at least 2 weeks prior to randomization.

15 Major Eligibility Criteria (continued) Formalin fixed, paraffin embedded tumor sample from the primary tumor is mandatory Adjuvant patients- surgical specimen Neoadjuvant patients- both pre-treatment biopsy specimen and the surgical specimen with residual disease are requested but only 1 is mandatory.

16 Patient Reported Outcomes Patient population will have intensive treatments with chemotherapy, surgery, and possible radiation prior to randomization. In this trial, there is an important opportunity to determine whether or not olaparib delays recovery after primary breast cancer treatment. Since fatigue has been the most common side effect reported with olaparib, it is the primary outcome in this comparison.

17 Administration of the PRO Questionnaires FACIT-Fatigue and EORTC QLQ-C30 questionnaires will be collected at - Baseline - 6 months (24 weeks) - 12 months (52 weeks) - 18 months - 24 months

18 Clinical Logistics IRB Approval Site Activation Site Initiation Visit (SIV) B-55 Lab Kit Registration Form

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21 REMINDER Update your Kit Registration Form anytime there is a change in the information you provided on the form.

22 Ordering Biospecimen Kits Initial Kit Order NSABP Web Site Access Kit Registration Form using your CTEP ID Order the kit Kits are site specific and cannot be transferred to other sites!

23 Biospecimen Kits Allow 3 weeks to receive the kits from Q2Solutions Large shipment- 10 boxes Some kit materials expire within 6 months

24 1. Flowchart Q2Solutions Manuals Specimen processing and shipping instructions 2. Laboratory Manual Completing Requisitions and general specimen collection information 3. Lab Manual for Anatomical Pathology Studies Tissue collection, processing and shipping

25 Biospecimen Kit Re-order Q2Solutions Supply Reorder Form CTSU web site B-55 Case Report Forms Enter your Q2Solutions Site Number on the form (5 digit number listed on kit registration confirmation from NRG Statistics and Data Management Center) Fax the completed form to Q2Solutions

26 Blood Samples to be Obtained During Screening Prior to Study Entry 2 Samples Are Required 1. Patients with unknown status (determine BRCA status) and patients with known BRCA mutation (confirmatory sample) 2. For assessment of current and future BRCA mutation assays

27 Shipping Samples Blood sample for BRCA testing Ship to Myriad the same day Marken is the courier for these shipments Marken Information Pack

28 Shipping Samples (continued) Q2Solutions - Blood sample for current and future BRCA mutation assays - Blood samples for biomarker analysis - Exploratory pharmacogenetics (Refer to the Flowchart) NRG Oncology Biospecimen Bank Pgh, PA Tumor samples

29 Pre-Registration Before shipping the BRCA specimen to Myriad Pre-register the patient in OPEN by submitting the Pre-Entry Step 1 form After submission, a print-out will be provided with an E-Code e.g The E-Code is the patient s study number and is required to be on blood tubes and requisitions sent to Myriad and Q2Solutions

30 BRCA Results Myriad ResultsNow secure online web portal Results sent by FedEx to the physician

31 NSABP B-55/BIG 6-13 Pathology and Correlative Science Instructions

32 Myriad Blood sample for BRCA testing NRG Oncology Biospecimen Bank, Pgh. PA Tumor samples Q2Solutions Blood sample for current and future BRCA mutation assays Blood samples for biomarker analysis Exploratory pharmacogenetics

33 Drug Ordering Responsibilities First drug order initiated by NRG Oncology SDMC- PIT at time of patient entry Allow 5 business days to receive study drug All subsequent orders by site staff through NCI PMB Online Agent Order Processing (OAOP)* *Must have CTEP IAM account

34 Management of Toxicity of Study Treatment Toxicity could be managed by interruption of the dose of study treatment or dose reductions. Doses that have been reduced may not be escalated.

35 Dose Reductions 300 mg. B.I.D Request the reduced dose through the NCI PMB OAOP Application

36 Concurrent anti-cancer therapy

37 Contact the Clinical Coordinating Department (CCD) regarding participation in another study or

38 Who to Contact with Questions Eligibility or clinical questions: Clinical Coordinating Department or Data management questions B-55 Data Manager, Adverse Event reporting questions B-55 AE Reporting Nurse,

39 Thank you for your attention!