Biomarker Screening Pilot MRC Clinical Trials Unit Overview

Biomarker Screening Pilot MRC Clinical Trials Unit

Overview • Background and project aims • Required site-set up for participation • Approaching patients to participate in biomarkerscreening • Pilot lab kit • Tumour block Collection logistics • Blood collection logistics • Saliva collection logistics • Sample Queries • Restocking kits MRC Clinical Trials Unit STAMPEDE

Background and project aims • Establish processes that enable retrieval and analysis of samples (saliva, blood and FFPE tumour tissue) within specified timelines • Establish pathology contacts in all sites where diagnostic tissue blocks may be stored. • Evaluate the feasibility of undertaking DNA/RNA sequencing using each sample type to inform the future approach to biomarker-screening MRC Clinical Trials Unit STAMPEDE

Rucaparib • Arm M of the study will contain Rucaparib which is a PARP inhibitor. • Patients will be defined as biomarker positive if a known relevant mutation is detected in a gene involved in DNA repair, this includes BRCA 1, BRCA 2, ATM and 11 other genes • Only patients that are biomarker positive will have the chance to be randomised into the Rucaparib arm. • All biomarker negative patients can enter the other arms of the study. • All suitable patients looking to enter the STAMPEDE study will need to complete biomarker analysis once the arm is greenlit at that site. • Sites that take part in the pilot will be accredited to start the new arm in the spring. MRC Clinical Trials Unit STAMPEDE

Required site-set up for participation • A variation to the clinical trials agreement (CTA) was put in place for the retrospective tumour block project (Variation Number 3). • All sites should have CTA variation 3 in place. • Most sites will not need new variation to the CTA as variation 3 states additional funding will be made available. • A signed STAMPEDE Histopathology Agreement will be required from all sites before being accredited to participate in the trial. MRC Clinical Trials Unit STAMPEDE

Approaching patients To be eligible to participate in the biomarker-screening pilot, patients are required to provide informed consent to both: • Main STAMPEDE study consent • Additional Research consent The following selection criteria must be met: • Confirmed metastatic disease (M 1) • Histologically confirmed prostate adenocarcinoma with recent tumour rich FFPE blocks (obtained within 8 months of registration) • If hormone therapy has started, FFPE tumour blocks should be sent within: • 8 weeks of the patient starting LHRH. • 10 weeks of starting anti-androgens. MRC Clinical Trials Unit STAMPEDE

Registration • Screening required prior to registration: Radiologically confirmed metastatic disease and minimum baseline bloods are required. Once eligibility for the biomarker screening pilot has been confirmed, the patient must be registered in order to proceed to biomarker screening. • Once patient consent has been obtained Form 01 A Registration CRF should be completed. • The patient can be registered for biomarker screening by phoning the MRC CTU at UCL on +44 (0) 20 7670 4777. While making sure to have the registration CRF to hand. • A registration ID will be provided by the STAMPEDE trial team. • The registration ID should be used on all data collection forms and correspondence with the MRC CTU at UCL prior to randomisation. MRC Clinical Trials Unit STAMPEDE

S-Stampede screening flowchart MRC Clinical Trials Unit STAMPEDE

Pilot lab kit Materials provide for each sample: Tissue sample 1 1 x x Registration ID label Plastic envelopes per sample Padded envelope (pre-paid postage) Test Request Form Blood sample 1 x Transport box 2 x 10 ml blood collection tubes (cell free DNA Streck TM tubes) 2 x Postal tubes 1 x Addressed padded envelope (pre-paid postage) 1 x S-STAMPEDE Blood CRF Saliva sample 1 1 2 1 1 1 x x x Saliva collection kit (Oragene DNA) Registration ID label Sample barcode Plastic envelope Sample Requisition form padded envelope (pre-paid postage) MRC Clinical Trials Unit STAMPEDE

Biomarker screening sample collections SAMPLE TYPE REGISTRATION 2 tumour rich FFPE tumour blocks obtained within 8 months of registration X# Blood X PRIOR TO PREPROGRESSION STARTING RESEARCH TREATMENT (48, 72 & 84 WEEKS) n/a X PROGRESSION X POST PROGRESSION, PRE-2 ND LINE TREATMENT X (Streck. TM tubes) Saliva X* # Two tumour rich FFPE blocks should be sent for testing (Almac Diagnostic) immediately following registration within the required hormone therapy timelines * Saliva sample using the Oragene 510 kit should be taken after registration MRC Clinical Trials Unit STAMPEDE

FFPE block analysis Key points • Please request the two most tumour rich FFPE tumour blocks obtained within 8 months prior to registration. • Please also complete the Test Request Form and send with the tumour samples when shipping to the central lab. • Almac diagnostics will contact sites regarding queries • Biomarker results are not required to randomise patients until the “rucaparib comparison” is active at your site • Funding for reimbursement per participant is available. A £ 60 payment will be made available on receipt of a tumour rich sample. An additional sum of £ 40 will be paid following successful DNA/RNA extraction and sequencing completed. MRC Clinical Trials Unit STAMPEDE

FFPE blocks - Processing and shipping • Place both FFPE tumour blocks belonging to one patient into one zip lock bag. • Complete a sample label and attach to each zip lock bag using the stickers provided. • Complete a Test Request Form and make 2 copies, send one with the samples, and retain one on-site. • Send to the Biomarker test provider, Almac Diagnostics using the pre -paid envelope provided. • Please ensure that the postage envelopes are securely fastened using tape or staples to ensure samples cannot fall out in transit. MRC Clinical Trials Unit STAMPEDE

Blood sampling • Similar to current sub-study blood sampling practise • Blood collection using cell free DNA Streck. TM tubes from which circulating tumour DNA can be extracted MRC Clinical Trials Unit STAMPEDE

Blood sampling - Processing and shipping • Complete label on blood collection tubes, add the registration ID • Collect 2 x 10 ml blood using Streck. TM tubes • Invert 8 to 10 times • No onsite processing required • Store at room temperature • Complete S-STAMPEDE CRF • Post samples and CRFs – within a maximum of 5 days to the ICR MRC Clinical Trials Unit STAMPEDE

Saliva sampling • Color Genomics will supply Oragene 510 saliva kits for the Biomarker-screening pilot study. These kits are different to the Oragene 500 saliva kits. MRC Clinical Trials Unit STAMPEDE

Saliva sampling- Processing and shipping • Adhere one of the barcode labels onto the Sample Requisition Form. Barcodes • Complete sample ID label and stick to the sample tube avoiding covering the barcode. • Place the sample into the sealable plastic bag and put into the original packaging. • Once completed seal the kit into the pre-paid envelope provided. MRC Clinical Trials Unit STAMPEDE

Queries - Almac diagnostics • Almac will direct queries at site by email and phone. • The CTU will occasionally contact sites regarding escalated queries • Examples of queries • Registration number on documents does not match sample labelling. • Documentation not correctly completed MRC Clinical Trials Unit STAMPEDE

Restocking kits • 2 lab kits will be sent to sites. • The CTU will send out a new kit once Almac have confirmed a site has sent a tissue sample for analysis. • If a site believes they may see more then 2 suitable patients at one time please contact the STAMPEDE inbox as soon as possible. MRC Clinical Trials Unit STAMPEDE

Questions? MRC Clinical Trials Unit STAMPEDE