Nektar Therapeutics (Nasdaq: NKTR) today announced positive results from a Phase 2 clinical study evaluating single-agent NKTR-102 in women with platinum-resistant/refractory ovarian cancer. A total of 68 patients were enrolled with platinum-resistant disease, half of whom were platinum refractory. All 68 patients were evaluable for the primary endpoint of objective response rate using Gynecologic Cancer InterGroup (GCIG) criteria, which is a combination of response by tumor imaging (RECIST) and/or ovarian cancer biomarker (CA-125) criteria. GCIG (confirmed and unconfirmed) response rates were 41 percent (14/34) in the once every 14 days (q14d) dose schedule and 41 percent (14/34) for the once every 21 days (q21d) dose schedule. Confirmed objective GCIG response rates were 29 percent (10/34) and 38 percent (13/34) in the q14d and q21d dose schedules, respectively. Confirmed and unconfirmed objective response rates using RECIST were 24 percent (8/33) and 29 percent (9/31) for the q14d and q21d dose schedules, respectively. Confirmed objective response rates using RECIST were 21 percent (7/33) and 23 percent (7/31) for each dose schedule, respectively.
"NKTR-102 has an exceptionally high response rate compared to what would be expected in this group of heavily pre-treated women with platinum-resistant and refractory ovarian cancer," said Prof. Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, European Union and Lead Investigator of the NKTR-102 study. "The impressive and rapid-onset treatment effect is particularly significant considering 71 percent of platinum-resistant patients had progressed within three months of their last platinum dose with a median of three prior cancer treatments. Based upon data from the GINECO cooperative group studies, RECIST response rates are typically below 10 percent for patients such as these. In addition, the median progression-free survival of eighteen weeks is considerably longer than would be expected in women with a median platinum-free interval of only one month. These results demonstrate that NKTR-102 holds great therapeutic potential for women battling ovarian cancer."
Approximately 48 percent (31/64) of the women in the study showed clinical benefit with single-agent NKTR-102, with a clinical benefit rate of 52 percent (17/33) in the q14d regimen and 45 percent (14/31) in the q21d regimen. Confirmed response rates for women that failed prior pegylated liposomal doxorubicin (PLD) therapy were 20 percent (3/15) for the q14d regimen and 29 percent (4/14) for the q21d regimen. NKTR-102 demonstrated a median progression-free survival of eighteen weeks as compared to a prior median platinum-free interval of four weeks. Confirmed CA-125 response rates were 38 percent (11/29) for both dose schedules.
"NKTR-102's clinical performance in platinum-refractory patients is particularly notable and provides a compelling rationale for accelerated development in this patient population," commented Robert L. Coleman, M.D., a leading ovarian cancer specialist and Director of Clinical Research, Department of Gynecologic Oncology, at The University of Texas M. D. Anderson Cancer Center, Houston, TX. "Rapid entry of NKTR-102 into Phase 3 development in women with less heavily pre-treated recurrent ovarian cancer is of great interest to the gynecologic cancer community."
NKTR-102 was generally well tolerated, particularly at the q21 dose schedule. The most common Grade 3 and 4 side effects were diarrhea, dehydration, hypokalemia, fatigue, nausea and neutropenia, with most side effects being Grade 3 in severity.
NKTR-102 Phase 2 Study Results
P2 Study of NKTR-102 in Women with Platinum Resistant/Refractory Ovarian Cancer (Abstract #5013) – Sunday, June 6, 2010, 11:15 a.m. – 11:30 a.m. CT, E Arie Crown Theater
The NKTR-102 Phase 2 Study was an international, multicenter, open-label, randomized, two-stage study to evaluate NKTR-102 when given either on a q14d or q21d regimen in women with platinum-resistant/refractory disease to any line of platinum-based chemotherapy (platinum-free interval <6 months). Median lines of prior therapy for women enrolled in the study were three, with 47 percent of the women having failed prior treatment with pegylated liposomal doxorubicin (PLD). Of the 71 patients enrolled, 68 were platinum-resistant, and of these 34 were platinum-refractory (3 patients had platinum-sensitive disease and were excluded from efficacy results). The primary endpoint of the study was objective response rate (based on RECIST and GCIG response criteria). Secondary endpoints were safety, progression-free survival and overall survival. Three patients in the study remain on NKTR-102 treatment.