Lowery MA, et al. – The combination of ADI–PEG 20 plus nab–paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma, was assessed for its efficacy. In combination with gemcitabine and nab–paclitaxel, ADI–PEG 20 was well tolerated. Researchers reported the activity in previously treated and untreated patients with advanced pancreatic cancer and in patients with argininosuccinate synthetase (ASS1)–deficient and –proficient tumors.

Methods

• They performed a single-arm, nonrandomized, open-label, phase 1/1B, standard 3 + 3 dose escalation with an expansion cohort of 9 patients at the recommended phase 2 dose (RP2D).
• This study entailed patients who had metastatic pancreatic cancer, up to 1 line of prior treatment (the dose-escalation cohort) or no prior treatment (the expansion cohort), and an Eastern Cooperative Oncology Group performance status of 0 to 1.
• Both gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) for 3 of 4 weeks and intramuscular ADI-PEG 20 at 18 mg/m2 weekly (cohort 1) or at 36 mg/m2 weekly (cohort 2 and the expansion cohort) had been administered to patients.
• Moreover, the primary endpoint was to determine the maximum tolerated dose and RP2D of ADI-PEG 20 in combination with nab-paclitaxel and gemcitabine.

Results

• This study incorporated eighteen patients.
• They did not find any dose-limiting toxicities (DLTs) in cohort 1.
• Because of 1 DLT occurrence (a grade 3 elevation in bilirubin, aspartate aminotransferase, and alanine aminotransferase), cohort 2 was expanded to 6 patients.
• Neutropenia, thrombocytopenia, leukopenia, anemia, peripheral neuropathy, and fatigue were the most frequent adverse events (AEs) of any grade.
• They reported grade 3/4 AEs in all 18 patients.
• Regardless of the relation with any drugs, neutropenia (12 patients or 67%), leukopenia (10 patients or 56%), anemia (8 patients or 44%), and lymphopenia (6 patients or 33%) were the most frequent grade 3/4 toxicities.
• It was noted that the RP2D for ADI-PEG 20 was 36 mg/m2 weekly in combination with standard-dose gemcitabine and nab-paclitaxel.
• 45.5% (5 of 11) was the overall response rate among patients treated at the RP2D in the first-line setting.
• For these patients treated at the RP2D, the median progression-free survival time was 6.1 months (95% confidence interval, 5.3-11.2 months), and the median overall survival time was 11.3 months (95% confidence interval, 6.7 months to not reached).