NSGO CLINICAL TRIALS IN OVARIAN CANCER UPDATE

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1 NSGO CLINICAL TRIALS IN OVARIAN CANCER UPATE

2 Niraparib and niraparibbevacizumab combination against bevacizumab alone in Women with Homologous Recombination eficient (HR) platinumsensitive epithelial ovarian, fallopian tube, or peritoneal cancer. ENGOTOV24 NSGO / AVANOVA EudraCT number: ASCO 2016 Gynecologic Cancer Session Type: Poster Session ate and Time: 06/06/2016 1:00 PM 4:30 PM Abstract Title: The ENGOTOV24/AVANOVA1 trial Abstract I: 5555 Sponsor: NSGO Project Manager: Louisa Boufercha Statistitian: epont Christensen PI: Mirza

3 ENGOTOV24 NSGO / AVANOVA Phase 1 (Completed) ose Escalation from cohorts 1 to 2 to 3 to 4 Cohort 1 Niraparib 100mg + Bev 15mg Cohort 2 Niraparib 200mg + Bev 15mg Cohort 3 Niraparib 300mg + Bev 15mg Cohort 4 Niraparib 300mg + Bev 7.5mg No ose Limiting Toicity Escalate to cohort 2 No ose Limiting Toicity Escalate to cohort 3 Bev related toicity Consider cohort 4 Recommended Phase 2 ose (RP2) of bevacizumabniraparib combination Niraparib 300mg daily + Bevacizumab 15mg/kg q 3 wks

4 ENGOTOV24 NSGO / AVANOVA Phase 2 design Randomization: 1:1:1 n=132 Platinumsensitive Ovarian Cancer Homologous Recombinatio n eficiency (HR) positive score Randomize ARM A Bevacizumab 15mg/kg q3w ARM B Niraparib 300mg O d121 ARM C Bevacizumab 15mg/kg q21d + Niraparib 300mg O d121 Treat to P/toicity Treat to P/toicity Treat to P/toicity Switch over to Niraparib 300mg O d121 Investigator s choice (without niraparib) Stratifications BRCA status: BRCA mutated vs. noncarrier Prior receipt of antiangiogenic therapy (yes/no) Prior lines of therapy: 13 vs > 3 lines

5 ENGOTOV24 NSGO / AVANOVA Study Status Part 1 Completed Part 2 Screening in K Activations ongoing in SWE Submissions completed in (NOR, FIN) FA & IRB submissions in May

6 A Phase 2 Randomized Umbrella Trial in Recurrent Ovarian Cancer NSGOOVUMB1 ENGOTOV30 Sponsor: Study Chair: Nordic Society of Gynaelogical Oncology (NSGO) MR Mirza Lead Investigators by participating groups: MR Mirza: Nordic Society of Gynaecological Oncology (NSGO) C Gourley: The Scottish Gynaecological Cancer Trials Group (SGCTG) A Oza: The Princess Margaret Hospital Consortium (PMHC) I Vergote: Belgian Gynaelogical Onology Group (BGOG) M Friedlander: The Australia New Zealand Gynaecological Oncology Group (ANZGOG) J Barek: Cooperative Ovarian Cancer Group for Immunotherapy (COGI) K Fujiwara: Gynecologic Oncology Trial and Investigation Consortium (GOTIC) SY Ryu: Korean Gynaelogical Onology Group (KGOG) G Coukos Ludvig Cancer Research Centre, Switzerland Suported by:

7 NSGOOVUMB1 Endpoints Primary endpoint: ProgressionFree Survival (PFS) by RECIST Secondary endpoints: PFS by ImmuneRECIST PFS at 9 months PFS at 12 months Median PFS PFS in each group according to trial stratification factors Overall survival for each eperimental arm Objective response rate (ORR) isease control rate (CR) (CR+PR+S) uration of (Overall) Response Patient Related Outcomes (PROs) Safety and tolerability.

8 NSGOOVUMB1 Key Inclusion Criteria Relapsed ovarian cancer with TFIchemo either < 6months or 6months. Patients with TFIchemo of 6months must have received 3 courses of chemotherapy. Highgrade serious, endometriod, undifferentiated. Apart from these types a limited number of low grade serious carcinoma, clearcell carcinoma and mucinous carcinoma can be enrolled in this study maimum of 5 patients per study cohort. Patient agrees to undergo all analysis (blood, serum, tissue) including tumor biopsy. ECOG performance status 01 Serum albumin >30g/l.

9 Relapsed ovarian cancer Tumor biopsy Tumor biopsy At progression NetGeneration Sequencing if required 3:1 randomization In each cohort Crossover in Standard arm permitted Cohort A urvalumab Coordinating Lead Group SGCTG Standard of care NSGOOVUMB1 Cohort B urva + AZ5069 Coordinating Lead Group PMHC Standard of care PETCT, tumor, blood, plasma and serum samples Cohort C urva + AZ9150 Coordinating Lead Group NSGO Standard of care PETCT, tumor, blood, plasma and serum samples Continous blood, plasma and serum samples Treatment until disease progression Suported by:

10 NSGOOVUMB1 Eperimental Treatment Arms uration of treatment: Until progression of disease or intolerable toicity Treatment schedule Abbreviations: C=cycle; =day; IBW=ideal body weight; IV=intravenous; PO=by mouth. 7day LeadIn Treatment Cycle 1 (and beyond) 28 days C1 Week 1 C1 Week 2 C1 Week 3 C1 Week Treatment cohort A: MEI4736 alone MEI4736 (10mg/kg IV) Treatment cohort B: AZ5069 in combination with MEI4736 AZ5069 (mg BI, PO) Medi4736 (mg/kg IV) Treatment cohort C: AZ9150 in combination with MEI4736 AZ9150 (mg/kg IBW IV) Medi4736 (mg/kg IV)

11 NSGOOVUMB1 Study Status Initial grant from AZ received Kickoff meeting of Steering Committee Meeting (Feb 20, 2016, London) Major grant application for study cohorts AC submitted (March 1, 2016) istribution of responsibilities being agreed between the lead groups & sponsor (NSGO) Planned submissions June 2016 Net wave of molecules/combinations under discussion