Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

Brief summary public domain (ClinicalTrials.gov)

This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen: • nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin The study will be conducted in two parts: Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT) [From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days]. Count Of Participants, Participants. Dose Exploration: Cohort 1 (n=7): 2; Dose Exploration: Cohort -1 (n=7): 1; Dose Exploration: Cohort -2B (n=10): 2; Dose Exploration: Cohort -3 (n=7): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Progression Free Survival (PFS) [RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).]. Median, months (95% Confidence Interval). Dose Exploration: Cohort 1 (n=7): 9.7 (2.96 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.]; Dose Exploration: Cohort -1 (n=7): 32.3 (0.53 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.]; Dose Exploration: Cohort -2B (n=10): 9.2 (0.46 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.]; Dose Exploration: Cohort -3 (n=7): 3.8 (1.22 to 5.78); Dose Expansion: Cohort -1 (n=25): 9.2 (7.59 to 11.20); Cohort -1: Pooled (n=32): 9.2 (7.59 to 11.96).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Best Overall Response (BOR) [RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).]. Count Of Participants, Participants. Dose Exploration: Cohort 1 (n=7): 2; Dose Exploration: Cohort -1 (n=7): 6; Dose Exploration: Cohort -2B (n=10): 4; Dose Exploration: Cohort -3 (n=7): 4; Dose Expansion: Cohort -1 (n=25): 20; Cohort -1: Pooled (n=32): 26.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Response Rate (ORR) [RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).]. Number, percentage of participants (95% Confidence Interval). Dose Exploration: Cohort 1 (n=7): 0 (0 to 41.0); Dose Exploration: Cohort -1 (n=7): 42.9 (9.9 to 81.6); Dose Exploration: Cohort -2B (n=10): 30.0 (6.7 to 65.2); Dose Exploration: Cohort -3 (n=7): 14.3 (0.4 to 57.9); Dose Expansion: Cohort -1 (n=25): 32.0 (14.9 to 53.5); Cohort -1: Pooled (n=32): 34.4 (18.6 to 53.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (DCR) [At Week 16]. Number, percentage of participants (95% Confidence Interval). Dose Exploration: Cohort 1 (n=7): 42.9 (9.9 to 81.6); Dose Exploration: Cohort -1 (n=7): 71.4 (29.0 to 96.3); Dose Exploration: Cohort -2B (n=10): 40.0 (12.2 to 73.8); Dose Exploration: Cohort -3 (n=7): 28.6 (3.7 to 71.0); Dose Expansion: Cohort -1 (n=25): 72.0 (50.6 to 87.9); Cohort -1: Pooled (n=32): 71.9 (53.3 to 86.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Overall Survival (OS) [RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).]. Median, months (95% Confidence Interval). Dose Exploration: Cohort 1 (n=7): 12.6 (3.98 to 21.03); Dose Exploration: Cohort -1 (n=7): 12.5 (0.53 to 12.71); Dose Exploration: Cohort -2B (n=10): 16.6 (0.69 to 26.74); Dose Exploration: Cohort -3 (n=7): 5.8 (1.35 to 14.65); Dose Expansion: Cohort -1 (n=25): 12.7 (8.18 to 23.66); Cohort -1: Pooled (n=32): 12.6 (8.74 to 19.12).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Duration of Response (DoR) [RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).]. Median, months (95% Confidence Interval). Dose Exploration: Cohort -1 (n=2): 28.4 (3.52 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.]; Dose Exploration: Cohort -2B (n=1): NA (NA to 16.39) [Median and lower limit of confidence interval was not evaluable due to below the level of detection.]; Dose Expansion: Cohort -1 (n=4): 9.4 (2.20 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.]; Cohort -1: Pooled (n=6): 9.4 (3.52 to NA) [Upper limit of confidence interval was not evaluable due to below the level of detection.].