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

2. 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

3. 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+)

4. 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

5. 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

6. 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

7. 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

8. 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%

9. 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

10. 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

11. 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