Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with advanced pancreatic adenocarcinoma (NCT03665441)

518 Background: Eryaspase, asparaginase encapsulated in red blood cells is an investigational product under development. The encapsulated asparaginase induces the degradation of asparagine and glutamine, crucial for cancer cell growth and survival. An earlier Phase 2b study in patients with advanced pancreatic cancer showed an improvement in overall survival (OS) and progression free survival (PFS) with eryaspase plus chemotherapy. Methods: TRYbeCA-1 was a randomized, open-label Phase 3 trial of eryaspase combined with chemotherapy in patients with advanced adenocarcinoma of the pancreas who have progressed on only one prior line of systemic anti-cancer therapy. Patients were randomized in a 1:1 ratio to gemcitabine/nab-paclitaxel or irinotecan/fluorouracil (5FU) therapy (depending on first-line received) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria included progression on or following first-line systemic treatment, ECOG performance status 0 or 1, stage III-IV disease, documented evidence of disease progression, available tumor tissue and adequate organ function. The primary endpoint was OS. A total of 412 events were required for 90% power to detect a treatment effect hazard ratio (HR) of 0.725 at a two-sided significance level of 5%. Results: A total of 512 patients were included. Baseline characteristics were well balanced between the treatment arms. The study did not meet the OS primary endpoint [HR: 0.92 (95% confidence interval (CI), 0.76-1.11), p-value 0.375]. The median OS for patients treated with eryaspase plus chemotherapy was 7.5 mo (95% CI, 6.5-8.3), compared to 6.7 mo (95% CI, 5.4-7.5) for chemotherapy alone. There was a trend of nominal OS benefit in 107 patients treated with eryaspase and irinotecan-5FU compared to 109 patients in control subgroup, with a median OS of 8.0 mo versus 5.7 mo, respectively [HR: 0.81 (95% CI: 0.60- 1.09)]. Treatment effect was consistent across various prognosis factors. Median PFS was 3.7 mo vs. 3.5 mo in the eryaspase and control arms, respectively [HR: 0.89 (95% CI: 0.73-1.07), p-value 0.215]. Disease control rate was 57.6% and 49.0% (p-value 0.047) in the eryaspase and control arms, respectively. The most common adverse events were in the eryaspase arm were asthenia, diarrhea, and anemia (Grade 3-4: 16.9%, 7.66% and 17.3%, respectively). Eryaspase did not appear to enhance toxicity of chemotherapy. Conclusion: This large prospective study did not meet it primary endpoint of improving OS in patients treated with eryaspase. The addition of eryaspase demonstrated nevertheless a well-tolerated profile and an encouraging survival benefit in the irinotecan/5FU subgroup, warranting further investigation. Clinical trial information: NCT03665441.