Evaluation of maintenance mono-immunotherapy to improve outcomes in advanced ovarian cancer (OV CA)

Abstract

5507 Background: Translating cancer specific immune stimulation into clinical benefit is a challenge. This ph III study tested the hypothesis that oregovomab (o) mono-immunotherapy IT following front-line therapy in a selected patient population pt would prolong time-to-relapse TTR and ultimately survival. The population was identified in an exploratory analysis of an earlier ph IIb study. O binds circulating CA125 stimulating a cellular immune response targeting CA125 and tumor. Method: Stage III/IV OV CA pts with <2 cm residual disease, CA125 <65 U/nl prior to cycle 3 and NED with CA125 5–35 at end of primary therapy were randomized to o or placebo (pbo) in a double blind protocol. 2 mg of o or pbo was infused at wks 0, 4, and 8 and then q12 wks until recurrence or year 5. Pts received serial imaging and/or clinical evaluation for recurrence q12 wks. TTR was primary endpoint. The protocol was divided into two identical studies 17A &17B each with 80% power at α=0.05 to detect a 6 m difference in TTR with N=177 randomized 2:1 to permit internal independent confirmation of results. Result: 371 pts were accrued at >60 centers, 251 to o and 120 to pbo. The arms were well balanced except for distant metastasis at staging which were observed in 17% of o but only 8% of pbo pt at staging CT. There were no differences in the clinical outcomes between treatment groups. TTR measured from randomization 4–12 weeks post completion of carboplatin- paclitaxel based chemotherapy was 10.3 m [9.7,13.0] for o and 12.9 m [10.1, 17.4] for pbo p=0.29 log rank test. Results were consistent in 17A&B. The treatment was well tolerated. The incidence of serious adverse events was 19% for pbo and 14% for o, mostly related to disease progression. Grade 3/4 toxicity was reported in 25% of pbo and 20% of o pts respectively. There were no differences in quality of life scores. Conclusion: Although o has demonstrated bioactivity, the strategy of monoIT is not effective as maintenance therapy following front-line treatment of advanced OV CA. The treatment was not associated with additive toxicity. Recent data demonstrating that schedule-sensitive concomitant chemoIT results in more vigorous immune stimulation than monoIT suggests that future studies of this or other tumor antigen specific immunization strategies focus on primary concurrent chemoIT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Unither, Inc.