204 Background: In the phase 3 MPACT study, treatment with nab-P + G resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in patients with metastatic PC, suggesting the potential for activity against LAPC. This international, multicenter single arm, phase 2 trial (LAPACT) was designed to evaluate the efficacy and safety of an induction phase regimen of nab-P + G in previously untreated patients with LAPC. Methods: Treatment-naive patients with unresectable LAPC and Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 were enrolled. The induction phase was designed as 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 on D 1, 8, and 15 of each 28-day cycle. After induction, patients without progressive disease or unacceptable adverse events were eligible for continued treatment with nab-P + G, chemoradiation, or surgery per investigator’s choice (IC). Surgery could occur prior to completing 6 induction cycles if the investigator deemed there had been a sufficient tumor response. The primary endpoint was time to treatment failure (TTF) in patients treated with nab-P + G as induction therapy followed by IC treatment. Key secondary endpoints included disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 107 patients enrolled, 106 were evaluable for the safety analysis. No new toxicities were identified. The most common grade ≥ 3 treatment-emergent adverse events during induction were neutropenia (42%), anemia (11%), and fatigue (10%); grade 3 peripheral neuropathy occurred in 4% of patients. The most frequent reasons for discontinuing induction were adverse events (18%) and progressive disease (7%). Forty-six (43%) patients received IC treatment after induction: 13 (12%) continued nab-P + G, 17 (16%) received chemoradiation, and 16 (15%) underwent surgical resection (R0, n = 7; R1, n = 9). DCR and ORR during induction were 78% and 35%, respectively; with a median TTF of 8.6 months and median PFS of 10.2 months. Conclusion: A nab-P + G induction regimen in LAPC appears tolerable and feasible and is associated with encouraging antitumor activity and promising TTF and PFS. NCT02301143. Clinical trial information: NCT02301143.
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.
358 Background: Treatment options for pts with LAPC are limited and generally similar to those for metastatic PC (mPC). The phase 3 MPACT trial of pts with mPC demonstrated a > 3-fold shrinkage of primary tumors with nab-P + G vs G, suggesting the potential of nab-P + G for LAPC treatment. Here, we present interim results on disease control rate (DCR), adverse events (AEs), and quality of life (QoL) from the international phase 2 LAPACT trial. Methods: Pts with treatment-naive unresectable LAPC and ECOG performance status of 0 or 1 received 6 cycles (C) of nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 of each 28-day C. After the initial nab-P + G treatment phase, pts without PD and unacceptable AEs were eligible for investigator’s choice (IC) of continued treatment with nab-P + G, chemoradiation, or surgery. Surgery could occur prior to completing 6 C in the case of a major response. Pt-reported QoL was assessed via EORTC QLQ-C30 and QLQ-PAN26 questionnaires at screening and prior to infusion on day 1 of each C. Results: As of Aug 17, 2016, 47 pts completed (28/47, 60%) or discontinued (19/47, 40%) the initial nab-P + G treatment (median, 5 C). Median age was 66 years (range, 44 - 86). The most frequent reasons for discontinuation were AE (10/47 [21%], with the most common being neutropenia and abnormal liver function [2 pts each]) and PD (3/47, 6%). The most common grade ≥ 3 AEs were neutropenia (34%) and anemia (11%). The DCR ≥ 16 weeks was 76% (34/45 efficacy-evaluable pts [defined as having evaluable baseline and ≥ 1 postbaseline scan]; PR, n = 13; SD, n = 21). Twenty-two pts (47%) were assigned by the investigators to an IC treatment: 4 (9%) to continue nab-P + G, 8 (17%) to chemoradiation, and 10 (21%) to surgical resection. Mean QoL scores remained stable during the study, with improved symptom scores for appetite and pain. During the initial nab-P + G treatment phase, most patients reported a complete resolution of certain limitations, including depression (≈ 80%), constipation (≈ 62%), and nausea (≈ 93%). Conclusions: These interim results suggest that for pts with LAPC, nab-P + G is tolerable and produces a promising DCR. On average, QoL scores remained stable during nab-P + G treatments. Clinical trial information: NCT02301143.
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