BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

In light of the central role of extracellular signal-regulated kinases (ERK) in pancreatic cancer, the investigators propose a phase I study to evaluate the ERK inhibitor BVD-523 at the recommended phase 2 dose in combination with nab-paclitaxel plus gemcitabine in patients with newly diagnosed metastatic pancreatic cancer. The primary endpoint will be maximum tolerated dose (MTD) or RP2D and safety. The secondary endpoints include safety, response rate, biochemical response, progression-free survival (PFS) and overall survival (OS). The exploratory endpoints include the assessing the impact of BVD-523 on the MEK/ERK pathway and other major pathway pertain to pancreatic cancer.

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

Maximum Tolerated Dose (MTD) of BVD-523 [Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient]. Number, mg. Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine (n=10): 450.

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

Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events [30 days after completion of treatment (median time was 67.5 days)]. Count Of Participants, Participants. Grade 1/2 Hearing Impaired: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 blurred vision: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 3; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 3 abdominal infection: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 constipation: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 5; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 2. Grade 1/2 diarrhea: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 5; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 4. Grade 3 diarrhea: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 2; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 dry mouth: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 2; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 dyspepsia: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 1/2 flatulence: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 gastrointestinal pain: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 mucositis oral: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 2; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 2. Grade 1/2 nausea: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 5; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 3 nausea: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 1/2 taste change: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 vomiting: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 0; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 3 vomiting: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 2; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 1/2 acute kidney injury: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 3 lower GI hemorrhage: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 chills: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 3; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 1/2 edema limbs: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 3; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 1. Grade 1/2 edema trunk: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 1; 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 0. Grade 1/2 fatigue: 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=12): 3; 450 mg BVD-523/Nab-paclitax

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

Response Rate [Through completion of treatment (median time was 37.5 days)]. Count Of Participants, Participants. Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine (n=5): 2; Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine (n=2): 0.

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

Biochemical Response of Treatment Regimen [Through completion of treatment (median time was 37.5 days)]. Count Of Participants, Participants. Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine (n=7): 3; Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine (n=5): 1.

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

Time to Tumor Progression (TTP) [Up to 2 years]. Median, days (Full Range). Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine (n=5): 85 (63 to 243); Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine (n=2): 39.5 (30 to 49).

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

Progression-free Survival (PFS) [Up to 2 years]. Median, days (Full Range). Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine (n=5): 85 (63 to 243); Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine (n=2): 39.5 (30 to 49).

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

Overall Survival (OS) [Up to 2 years]. Median, months (95% Confidence Interval). 600 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 13.8 (10.7 to 22.8); 450 mg BVD-523/Nab-paclitaxel/Gemcitabine (n=6): 5.7 (1.1 to NA) [There were too few participants to provide upper estimate on the 95% confidence interval.].