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The
OReO
Study
Study design & ProtocolStudy design
Key Inclusion criteria Patient population
Recruitment and retention tools
A Phase IIIb, Randomised, Double-blind,
Placebo-controlled, multi-centre Study of
Olaparib Maintenance Re-treatment in
Patients with Epithelial Ovarian Cancer
Previously treated with a PARPi and
Responding to Repeat Platinum
Chemotherapy (OReO)
OReO/GINECOENGOT-ov38
Trial setting: non-mucinous EOC (including patients with fallopian tube
and/or primary peritoneal cancer)
Study Design: Phase IIIb, Randomised, Double-blind, Placebo-controlled,
Sponsor(s): AstraZeneca
Planned No. of patients: 416
Current accrual: First patient in June
Ongoing Trials – status update
• gBRCA+ or sBRCA+(n=136)
• 1 prior PARPi treatment
- 18mo+ after 1st line CT
- 12 mo+ after 2nd line CT
Stratification factors
• Prior bevacizumab
• <3 vs ≥3 chemo lines
2:1
*300 mg bid or last tolerable dose
R
A
N
D
O
M
I
Z
A
T
I
O
N
OReO Study: Olaparib Retreatmentin Platinum-Sensitive Ovarian Cancer
• BRCAve- all-comers(n=280)
• 1 prior PARPi treatment
- 12mo+ after 1st line CT
- 06 mo+ after 2nd line CT
RP/RCPlatinum-based chemotherapy
(no Bev)
PF
S,
TF
ST
, F
AC
T-O
, S
afe
ty,
AE
SI,
OS
Rational of prior PARPi exposure time
Median PFS of Study 19 (Olaparib) and NOVA (Niraparib) Patients According to BRCA Status and Treatment Arm, and Selection of Patients in OReO According to Previous Exposure to PARPi
BRCAm
placebo arm
late relapse
BRCAm
Olaparib arm
late relapse
BRCAwt
placebo arm
late relapse
BRCAwt
Olaparib arm
late relapse
Median PFS (months)
Study 19 4.3 11.2 5.5 5.6
NOVA 5.5 21.0 3.9 9.3
Selection in OReO
according to previous
PARPi exposure for
relapse patients
> 12 > 6
Selection in OReO
according to previous
PARPi exposure for first line
patients
> 18 > 12
Investigator meeting - 18/05/2017 4
➢ Response: CR or PR to most recent platinum CT (No Bevacizumab)
➢ Allowed subjects with additional line of chemo (+/- Bev) after PARPi and
prior to most recent platinum-based chemotherapy
➢ Entry based on length of first PARPi exposure
136 patients patients in a 2:1 ratio
STUDY DESIGN – BRCA1/2 (+VE) COHORT
Chemo OReO olap./plac.
1st line
PARPi
2nd line
Chemo PARPi
≥ 18 months
Chemo
Chemo OReO olaparib/placebo
Relapse *
R
within 8 weeks
≥ 12 months
BRCA+
• 18mo+ after 1st line CT
• 12 mo+ after 2nd line CT
5
Hazard ratio of olaparib maintenance versus placebo of 0.61
(corresponding to a median PFS of 12 months in placebo versus 24
months with olaparib)
➢ Response: CR or PR to most recent platinum CT (No Bevacizumab)
➢ Allowed subjects with additional line of chemo (+/- Bev) after PARPi and
prior to most recent platinum-based chemotherapy
➢ Entry based on length of first PARPi exposure
STUDY DESIGN – BRCA1/2 (-VE) COHORT
≥ 6 months
BRCA-ve
• 12 mo+ after 1st Line CT
• 6 mo+ after 2nd line+ CT
Chemo OReO olaparib/placebo
1st line
PARPi
2nd line
Chemo PARPi
≥ 12 months
Chemo
Chemo OReO olaparib/placebo
Relapse *
R
within 8 weeks
* an interval after stopping PARPi is allowed
6
280 patients patients in a 2:1 ratio
Hazard ratio of olaparib maintenance versus placebo of 0.73
(corresponding to 4.3 month (53.8%) increase in median PFS beyond the 8
months expected for patients on placebo)
STUDY OBJECTIVES
Primary Objective:
• To determine the efficacy of olaparib re-treatment compared to matching
placebo by assessment of Progression free survival (PFS).
Secondary Objectives:
• To determine the efficacy of olaparib re-treatment compared to
matching placebo by assessment of:
• Overall survival (OS)
• the use of subsequent therapies and study treatment discontinuation
• time to progression (TTP) by Gynecologic Cancer Intergroup (GCIG)
criteria
• To determine the Health-related Quality of Life (HRQoL) of olaparib re-
treatment compared to matching placebo as measured by the
Functional Assessment of Cancer Therapy – Ovarian (FACT-O)
Safety Objective:
• To evaluate the safety and tolerability of olaparib maintenance re-
treatment
• General safety (AEs/SAEs)
• Advers events of special interest (AESI)
• Clinical chemistry/haematology parameters (safety Lab data) 7