Single agent, canfosfamide (C, TLK286) vs pegylated liposomal doxorubicin (D) or topotecan (T) in 3rd-line treatment of platinum (P) refractory or resistant ovarian cancer (OC): Phase 3 study results

Abstract

LBA5528 Background: Canfosfamide (C) is a novel glutathione analog prodrug activated by glutathione S-transferase P1–1. P resistant OC has a poor prognosis and non-P agents are used for palliation. C reported objective responses in multicenter Phase 2 OC trials. Methods: Pts with P resistant OC who progressed after D or T, measurable disease (RECIST), adequate liver/renal/bone marrow function were eligible. Randomization was stratified by prior D or T treatment, ECOG PS (0 or 1 vs 2) and presence or absence of bulky disease (= 5cm). Patients received C at 1000 mg/m2 IV q3wks, or to D at 50 mg/m2 IV q4wks or T at 1.5 mg/m2 IV daily × 5 q3wks until progression. The trial had a 90% power to detect a 29% reduction in the relative risk of death. Results: 461 pts (C=232 and D or T=229) received 1052 cycles [median 3; range (r) 1–33], 699 (median 4; r 1–32), and 469 (median 5; r 1–21) for C, D and T respectively. Most common Grade 3–4 AEs for C were: nausea (31.6%), vomiting (8.7%), fatigue (6.1%), and anemia (5.6%), for D/T were: nausea (55.3%), anemia (15.2%), fatigue (6.9%), neutropenia (23.5%), thrombocytopenia (12.4%), febrile neutropenia (6%), stomatitis (6%), and PPE syndrome (6%). ORR for C was 4.3% including a CR, vs 10.9% ORR for D/T. Median survival (MS) was 8.5 mos for C, 13.6 mos for D/T (p=0.0001). Median progression-free survival was 2.3 mos for C and 4.4 mos for D/T, (p=0.0001). D/T MS was 14.2/10.8 mos, respectively. Conclusions: Canfosfamide did not meet the primary endpoint. C demonstrated single agent activity in P refractory or resistant OC and was well tolerated. C in combination with standard agents in less heavily treated OC trials are in progress. No significant financial relationships to disclose.