At the cut-off date, 204 patients were randomized to the ofra-vec arm and 205 to the control arm. A similar number of patients in each of the treatment arms continued study treatment until disease progression by RECIST and were considered as having completed treatment per protocol; 143 (70.1%) completers in the ofra-vec arm compared to 146 (71.2%) in the control arm.
Exposure to study medications was similar in both arms.
Demographic variables and baseline disease characteristics were as expected for the patient population recruited, were well balanced between the treatment arms, and showed only minimal differences, which would not be expected to impact the validity or interpretation of the results. Patients in both arms were heavily pre-treated.
All patients were considered platinum resistant or refractory, (excluding 2 patients (1%) in each arm who were enrolled despite not meeting this eligibility criterion).
Efficacy
All 204 patients in the ofra-vec arm and 205 in the control arm were evaluable for efficacy. The PFS primary endpoint was not met.
The secondary endpoint of ORR was also not.
Exploratory analyses compared the primary efficacy endpoints in various patient subgroups. The most significant results were obtained for the post-randomization subgroup of patients who had a CA-125 response (CR or PR), which was associated with substantially improved PFS and OS in both treatment arms. See full report for more details.
Safety
The safety analysis set included 406 patients with 203 in each of the two treatment arms. Ofra-vec was well tolerated as evidenced by a low rate of treatment discontinuations due to AEs; In the ofra-vec arm 8 patients [3.9%] discontinued ofra-vec/placebo due to an AE compared to 14 [6.9%] in the control arm, and 14 [6.9%] discontinued paclitaxel due to an AE compared to 20 [9.9%] in the control arm.
Almost all patients experienced at least one AE. Seven patients reported AEs with fatal outcomes; 3 in the treatment arm (pneumonia, AML, and hypovolemic shock) and 4 in the control arm (sepsis in 1 patient, sepsis and general physical health deterioration in 1 patient, sepsis and necrotizing fasciitis in 1 patient, and intestinal perforation in 1 patient). None of the fatal AEs was considered related to study treatment.
Serious AEs (SAEs) were reported by 63 (31.0%) patients in the ofra-vec arm and 54 (26.6%) in the control arm. Some SAEs were more commonly reported in the ofra-vec than the control arm. SAEs related to ofra-vec were reported by 12 (5.9%) in the ofra-vec arm; pyrexia (4 patients), anemia (2 patients), and infusion related reaction, pneumonitis, duodenal perforation, pulmonary embolism, fatigue, dehydration, cerebrovascular accident, deep vein thrombosis (one patient each). This compared to 6 (3.0%) patients in the control arm reporting SAEs related to ofra-vec/placebo; one case each of enterovesical fistula, anemia, pneumonitis, sepsis, febrile neutropenia, pulmonary embolism.
Grade ≥ 3 AEs were reported by 123 (60.6%) patients and 109 (53.7%) in the ofra-vec and control arms, respectively. Of these, 52 (25.6%) in the ofra-vec arm were considered related to ofra-vec/placebo compared to 30 (14.8%) in the control arm.
AEs considered related to ofra-vec or placebo were more common in the ofra-vec arm (183 [90.1%] patients) than in the control arm (154 [75.9%] patients). These events were generally low grade, responded well to antipyretic treatment and resolved within 1-2 days. These differences are expected based on the viral vector nature of ofra-vec.
No new or unexpected safety findings arose during the study. There was no increased incidence of AEs known to be associated with anti-angiogenic agents such as hypertension, proteinuria, gastrointestinal perforation, bleeding, hemorrhage. The pattern of AEs observed reflected the product’s established safety profile and was as expected for an adenovirus based viral therapy. See full report for more details.
Conclusions:
Neither the final PFS or interim OS primary endpoints were met, and the study could not support an efficacy claim in the overall population of patients PROC.
The two treatment groups were well balanced for all relevant background and demographic characteristics. Patients in both treatment groups were heavily pre-treated with a mean of 3 prior lines of anti-cancer therapies, and 60%-70% in each of the groups previously being treated with anti-angiogenics and/or PARP inhibitors. The PFS and ORR results of the control group exceeded the results that were anticipated based on historic results of the AURELIA chemotherapy control group.
In both treatment groups a CA-125 response was associated with substantially improved PFS and OS indicating that CA-125 response is a prognostic biomarker for patients with platinum-resistant ovarian cancer treated with paclitaxel.
