1. Farletuzumab in platinum sensitive ovarian cancer with low CA125
BGOG-ov18 Randomized Phase II of chemo +/- Farletuzumab
BGOG-ov18/Engot ov-27
Farletuzumab in platinum sensitive
ovarian cancer with low CA125
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Efficacy and Safety of Farletuzumab (MORAb-003) in Combination with Carboplatin plus Paclitaxel or Carboplatin plus Pegylated Liposomal Doxorubicin (PLD) in Subjects with Low CA125 Platinum‑Sensitive Ovarian Cancer   

2. BGOG-ov18 Randomized Phase II of chemo +/- Farletuzumab
Carbo PLD x6 + Farletuzumab : Concomittant + maintenance till PD
loading dose for the first 2 weeks of 10 mg/kg farletuzumab (double blind), followed by 5 mg/kg weekly
First recurrent platin sensitive high grade serous ovarian carcinoma
CA125 < 3UNL
Evaluable or measurable according to RECIST
N = 210
Carbo PLD
2:1
Carbo PLD x6 + Placebo : Concomittant + maintenance
Investigator Choice
1:1
Carbo Pacli + Farletuzumab : Concomittant + maintenance till PD
loading dose for the first 2 weeks of 10 mg/kg farletuzumab (double blind), followed by 5 mg/kg weekly
Carbo Pacli
2:1
Carbo Pacli x6 + Placebo : Concomittant + maintenance
FPI: Mar 2015 (US); Aug 2015 (EU)
ENGOT Model: C
Primary endpoint: PFS * (Assumed HR = 0.667, investigator read)
Secondary endpoints: OS, Pt free interval, OR, TTR, DR, safety, PK and exposure-response

3. MORAb-003 (Farletuzumab)
BGOG-ov18/Farletuzumab
MORAb-003 (Farletuzumab)
Humanized IgG monoclonal antibody that binds to folate receptor alpha (FR-α)
FR-α highly expressed in epithelial ovarian cancer cells but largely absent from normal tissue
Farletuzumab (FAR) potentially has anti-tumor activity via antibody dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC)
CA125 has been shown to inhibit the in vitro ADCC activity of FAR

4. BGOG-ov18/Farletuzumab
Rationale
The primary results of the large phase III in platin sensitive ovarian cancer were reported at ESGO 2013 (Vergote et al, October 2013)
The primary result for PFS in the ITT population was not statistically significant in FAR treated groups
However improved PFS and OS was observed in a subgroup of patients with low CA125 (HR=.49 and .44 respectively)
Improved PFS and OS was also observed for those subjects with higher farletuzumab serum exposure levels, therefore testing new dose appears warranted

5. BGOG-ov18/Farletuzumab
Patient Population- 1st platinum sensitive relapse high grade serous EOC
Stratification:
individual chemotherapy treatment regimen (1:1 ratio)
platinum-free interval following first-line therapy (6-12 mos. vs >12‑36 mos.)
Statistical Design
Primary endpoint PFS (based on investigator read; central scans collected for confirmatory analysis)
85% power target PFS hazard ratio of 0.667 (33.3% risk reduction)
Total 143 PFS events (at least 68 PFS events in each of the chemotherapy strata)

6. BGOG-ov18/Farletuzumab
Objectives
Primary:
Farletuzumab has superior efficacy compared to placebo in improving progression-free survival (PFS) as determined by RECIST 1.1 when added to 1 of 2 standard chemotherapy regimens (carboplatin plus paclitaxel or carboplatin plus PLD) in subjects with platinum-sensitive ovarian cancer in first relapse who have a CA125 ≤ 3x the upper limit of normal (ULN) at study entry.
Secondary:
Overall survival (OS)
To assess the effect of Farletuzumab in prolonging second platinum-free interval longer than first platinum-free interval
To assess the effect of farletuzumab on best objective response (OR) rate, time to response (TTR) and duration of response (DR) by RECIST 1.1 criteria
To assess the safety and tolerability of Farletuzumab
To assess the pharmacokinetics and exposure-response relationships between Farletuzumab and PFS and OS

7. BGOG-ov18/Farletuzumab
Inclusion Criteria
CA125 ≤ 3xULN confirmed within 2 weeks of randomization using a centralized laboratory assay
A histologically confirmed diagnosis of high grade serous epithelial ovarian cancer including primary peritoneal and fallopian tube malignancies
Maintenance therapy after the first platinum-free interval is allowed; however, the last dose must have been at least 30 days before Randomization.
No cancer vaccine therapy is allowed.
Must have evaluable disease by CT or MRI scan, according to RECIST 1.1
Must have relapsed radiographically between 6 months and 36 months of completion of first-line platinum chemotherapy and should be randomized within 16 weeks of radiographic relapse

8. BGOG-ov18/Farletuzumab
RECIST-1.1 Assessments
CT/MRI of Chest, Abdomen and Pelvis will be performed
At Screening
Every 6 weeks in first 6 cycles (combination of test article with Chemotherapy)
Every 9 weeks thereafter (single agent test article maintenance therapy) until disease progression
The same method of assessment (e.g. CT scan, spiral CT scan MRI) should be used in all assessments
CT or MRI scans will be read locally for safety, medical management, and primary analysis
Subjects require baseline of CT of Chest, can otherwise be followed with MRI