Anti-LeY monoclonal antibody (mAb) hu3S193 (Rebmab 100) in patients with advanced platinum resistant/refractory (PRR) ovarian cancer (OC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC).

Abstract

5078 Background: Lewis-Y (LeY) antigen is a blood group related antigen expressed in 75% of OC. hu3S193 is a humanized anti-LeY IgG1 mAb with strong complement dependent cytotoxicity and excellent targeting characteristics with a good safety profile in Phase I studies. Methods: This phase II study accrued pts with PRR, OC, PPC or FTC, with LeY expression by IHC, ≤ 1 prior chemotherapy regimens in the PRR state, and a KPS ≥ 70%. Pts received weekly intravenous infusions (1 cycle = 8 weeks) of hu3S193 at 20mg/m2 for up to 3 cycles, until disease progression or unacceptable toxicity. Primary endpoint was clinical benefit rate [objective response (OR) + stable disease (SD) ≥ 24 weeks]. A two-stage design was utilized with H1 set at 15%, requiring at least 1 OR. Secondary objectives were safety, progression-free survival (PFS) and pharmacokinetics (PK). Results: 31 pts were enrolled. Median age: 55 yrs (range 25-78); primary site: OC-29, PPC-1 FTC-1; LeY-positive by IHC (N): 1+ (15), 2+ (5), 3+ (8), 4+ (3). Prior platinum response: refractory 8, primary resistant 8, secondary resistant 14, allergy 1; median KPS: 90% (range 70-100); median CA-125: 257 (range 18-10,041). Number of cycles of hu3S193 delivered: 32 (median 1, range <1-3). Evaluable patients: 26 (5 pts < 4 doses); Responses: OR=0; SD=11 (42%); SD ≥ 24 weeks=6 (23%). No grade 4 toxicities observed. Most frequent toxicities in all pts (N any grade/grade 3): fatigue 4/1, allergy 4/1, tremor 2/1, fever 3/0, nausea 4/0, hypertension 3/0. Median PFS was 10 weeks (95 % CI, 4-15). PK data will be presented. Conclusions: single agent hu3S193 induces disease stabilization in a significant rate in this heavily pretreated population, including long term stabilization. PFS is comparable to historic chemotherapy data with acceptable toxicity. Further studies in combination with chemotherapy are underway.