Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)

Brief summary public domain (ClinicalTrials.gov)

This is a phase 3 study to evaluate the efficacy of ibrutinib in combination with nab-paclitaxel and gemcitabine for the first line treatment of patients with metastatic pancreatic adenocarcinoma.

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

Progression Free Survival (PFS) [Results at an overall median follow-up of 24.87 months]. Median, Months (95% Confidence Interval). Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 5.32 (3.75 to 5.49); Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 6.01 (5.45 to 7.16). Analysis, Ibrutinib+Gemcitabine+Nab-paclitaxel vs Placebo+Gemcitabine+Nab-Paclitaxel: Hazard Ratio (HR) 1.525 (95% CI 1.241 to 1.873); p=<0.0001; Log Rank; superiority.

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

Overall Survival (OS) [Results at an overall median follow-up of 24.87 months]. Median, Months (95% Confidence Interval). Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 9.69 (8.57 to 10.41); Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 10.78 (8.94 to 11.66). Analysis, Ibrutinib+Gemcitabine+Nab-paclitaxel vs Placebo+Gemcitabine+Nab-Paclitaxel: Hazard Ratio (HR) 1.109 (95% CI 0.903 to 1.363); p=0.3225; Log Rank; superiority.

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

Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine. [Results at an overall median follow-up of 24.87 months]. Number, percentage of participants. Subjects with any TEAE >= Grade 3: Placebo+Gemcitabine+Nab-Paclitaxel (n=212): 86.8; Ibrutinib+Gemcitabine+Nab-paclitaxel (n=208): 85.6. Subjects with ibrutinib/pbo-related TEAE >=Grade 3: Placebo+Gemcitabine+Nab-Paclitaxel (n=212): 55.7; Ibrutinib+Gemcitabine+Nab-paclitaxel (n=208): 54.3.

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

Overall Response Rate [Results at an overall median follow-up of 24.87 months]. Number, percentage of Patients (95% Confidence Interval). Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 42.3 (35.5 to 49.2); Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 29.5 (23.3 to 36). Analysis, Placebo+Gemcitabine+Nab-Paclitaxel vs Ibrutinib+Gemcitabine+Nab-paclitaxel: Risk Ratio (RR) 0.695 (95% CI 0.535 to 0.903); p=0.0058; Cochran-Mantel-Haenszel; superiority.

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

Clinical Benefit Response [Results at an overall median follow-up of 24.87 months]. Number, percentage of patients. Achieved a >=50% reduction in pain intensity: Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 25.8; Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 27.5. >=20-pt improvement in KPS (>=4 consecutive weeks): Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 1.4; Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 0. Sustained weight gain (>=7% maintained >4 weeks: Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 11.7; Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 5.7.

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

Carbohydrate Antigen 19-9 (CA19-9) Response [Results at an overall median follow-up of 24.87 months]. Number, percentage of patients (95% Confidence Interval). Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 62.9 (56.0 to 69.4); Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 53.6 (46.6 to 60.4). Analysis, Placebo+Gemcitabine+Nab-Paclitaxel vs Ibrutinib+Gemcitabine+Nab-paclitaxel: Risk Ratio (RR) 0.850 (95% CI 0.722 to 1.0); p=0.0488; Cochran-Mantel-Haenszel; superiority.

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

Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). [Results at an overall median follow-up of 24.87 months]. Median, months (95% Confidence Interval). Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 6.14 (4.86 to 8.21); Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 4.21 (2.86 to 5.82). Analysis, Placebo+Gemcitabine+Nab-Paclitaxel vs Ibrutinib+Gemcitabine+Nab-paclitaxel: Hazard Ratio (HR) 1.265 (95% CI 0.975 to 1.642); p=0.0782; Log Rank; superiority.

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

Rate of Venous Thromboembolic Events (VTE) [Results at an overall median follow-up of 24.87 months]. Number, Percentage of Participants (95% Confidence Interval). Placebo+Gemcitabine+Nab-Paclitaxel (n=213): 10.8 (7.0 to 15.8); Ibrutinib+Gemcitabine+Nab-paclitaxel (n=211): 8.1 (4.8 to 12.6). Analysis, Placebo+Gemcitabine+Nab-Paclitaxel vs Ibrutinib+Gemcitabine+Nab-paclitaxel: p=0.3343; Chi-squared; superiority.