IMagyn050 YO39523 / GOG-3015 / ENGOT-ov39 Sandro Pignata

IMagyn050 YO39523 / GOG-3015 / ENGOT-ov39 Study Overview: Protocol A Phase III, multicenter, randomized, study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed Stage III or Stage IV ovarian, fallopian tube, or primary peritoneal cancer

IMagyn050: Study Design in Primary Surgery Cohort Previously untreated ovarian, fallopian tube, or peritoneal cancer Stage III w/macroscopic residual disease), Stage IV, or Unresectable advanced stage patients for neo- adjuvant therapy ECOG PS 0-2 Carboplatin AUC 6 q3wk Paclitaxel 175 mg/m2 q3wk R 1:1 Bev 15 mg/m2 q3wk Bev* 15 mg/kg X 16 cycles Placebo q3w X 22 cycles No cross-over Carboplatin AUC 6 q3wk Stratification variables Stage/debulking status ECOG PS PDL1 IC0 vs IC1+ Adjuvant/Neo-adjuvant Paclitaxel 175 mg/m2 q3wk Bev 15 mg/m2 q3wk Bev* 15 mg/kg X 16 cycles Atezo 1200 mg q3w X 22 cycles Co-Primary endpoint: PFS & OS in all comers and Dx+ (IC1+)

IMagyn050: Study Design in Neoadjuvant Cohort Previously untreated ovarian, fallopian tube, or peritoneal cancer Stage III / IV, Unresectable advanced stage patients for neoadjuvant therapy ECOG PS 0-2 R 1:1 Carboplatin AUC 6 Bev 15 mg/kg X 16 cycles Placebo q3w X 22 cycles Paclitaxel 175 mg/m2 Bev 15 mg/m2 Bev* 15 mg/kg X 16 cycles Atezo 1200 mg q3w X 22 cycles No cross-over SURGERY

IMagyn050: Study Outcome Measures Efficacy SEE PROTOCOL SECTION 6.4 Co-Primary PFS ITT population PDL1+ population OS Key Points OS may be the better endpoint for CIT trials -- CIT trials to date have had variable results with PFS, despite the OS being positive -- Maintaining the integrity of the OS endpoint is imperative. Survival follow-up (OS) continues after Study drug discontinuation and after Progression/Recurrence (PFS) -- Including:  After progression  After AE-related treatment discontinuation  After stopping Study drug for any reason  After starting a new regimen upon progression Documentation: -- Patient discontinues Study treatment, NOT the Study

IMagyn050: Study Outcome Measures Efficacy SEE PROTOCOL SECTION 6.4 Secondary Objective Response (Primary Surgery patients) Duration of Response (Primary Surgery patients) Patient-reported Ovarian Cancer Abdominal Symptoms (Neoadjuvant patients) Patient-reported function & HRQoL

IMagyn050: Study Outcome Measures Safety and PK SEE PROTOCOL SECTION 6.5 & 6.6 Safety Incidence, nature, &severity of AEs (CTCAE v4.0) Incidence of ATA to atezolizumab & correlation with PK, PD, safety, &efficacy PK Maximum (Cmax)& Minimum (Cmin) after infusion

IMagyn050: Study Hypothesis IMagyn050 will test the hypothesis that treatment with atezolizumab added to paclitaxel, carboplatin, and bevacizumab will prolong PFS and OS compared with treatment with placebo plus paclitaxel, carboplatin, and bevacizumab N = 1300 patients Neoadjuvant Chemotherapy cohort: approximately 20%

Exploratory Biomarker Objectives SEE PROTOCOL SECTION 6.7 Pharmacodynamic exploratory biomarkers in archival and/or fresh tumor tissue and blood & association with clinical outcome Molecular subtyping of ovarian cancer cell-free tumor DNA Identify biomarkers associated with resistance Association of tumor immune- related or disease type−related exploratory biomarkers (in archival and/or freshly obtained tumor tissues and plasma, whole blood, or serum) with clinical outcome; biomarkers may include but are not limited to the following: Relationship between biomarkers in blood and tumor tissue between pre-treatment and post- progression samples collected at disease progression. These biomarkers may include and not limited to: Acquired CD8 Changes in the tumor immune microenvironment and biology BRCA, HRD, MSI

IMagyn050: ENGOT Groups MITO (Lead group): Italy MaNGO: Italy AGO: Germany AGO: Austria BGOG: Belgium CEEGOG: Czech Republic GEICO: Spain GINECO: France HECOG: Greece NSGO: Denmark, Finland, Norway, Sweden PGOG: Poland TRSGO: Turkey

IMagyn050: Road to FPI with ENGOT in Europe 2017 Feb Mar Apr May Jun Jul Aug Sep Roche ENGOT - agreements ENGOT Regulatory Roche site startup 14 Feb: PSA signed 28 Feb: MSA development End-Jul: MSA signed Beg-Mar: Negotiate study and site budgets End-Mar: Site selection Mar: Feasibility End-Mar: VHP submission (protocol v2) Beg-Jun: VHP approval * Mid-Jun: Country HA submissions Parallel submission possible Mid-Jul: CTA approval Mid-Jun: EC submissions End-Jun: Contract negotiations End-Jul: FSA in EU * Assumes only one round of questions received during VHP review End-Aug: FPI in EU