A Study in Metastatic Cancer and Advanced or Metastatic Unresectable Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

Phase 1b: To determine the safe and tolerable dose of galunisertib in combination with gemcitabine in patients with solid malignancy Phase 2a: To compare the overall survival (OS) of patients with Stage II to IV unresectable pancreatic cancer when treated with a combination of galunisertib and gemcitabine with that of gemcitabine plus placebo.

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

Phase 1b: Recommended Phase 2 Dose [Time of first phase 1b dose until time of last phase 1b dose (up to 1 year)]. Number, milligrams (mg). Phase 1b Participants (n=14): 300.

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

Phase 2: Overall Survival (OS) [Baseline to date of death from any cause (up to 2 years)]. Median, Months (95% Confidence Interval). Phase 2: 300 mg Galunisertib + Gemcitabine (n=104): 8.9 (7.3 to 11.1); Phase 2: Placebo + Gemcitabine (n=52): 7.1 (5.8 to 9.0). Analysis, Phase 2: 300 mg Galunisertib + Gemcitabine vs Phase 2: Placebo + Gemcitabine: Hazard Ratio (HR) 0.794 (95% CI 0.590 to 1.085); Bayesian Analysis; superiority.

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

Phase 1b: Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 24 Hours (AUC[0-24], ss) and Time Zero to Infinity (AUC[0-∞], ss) [Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)]. Geometric Mean, nanogram*hour per milliliter (ng*h/mL) (Geometric Coefficient of Variation). AUC(0-24): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=3): 2530 (116); Phase 1b: 160 mg Galunisertib + Gemcitabine (n=2): NA (NA) [Not analyzed due to insufficient number of participants with enough PK samples.]; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=3): 9090 (27). AUC(0-∞): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=3): 2740 (117); Phase 1b: 160 mg Galunisertib + Gemcitabine (n=2): NA (NA) [Not analyzed due to insufficient number of participants with enough PK samples.]; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=3): 10600 (10).

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

Phase 1b: Pharmacokinetics: Maximum Plasma Drug Concentration at Steady State (Cmax,ss) [Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)]. Geometric Mean, nanogram per milliliter (ng/mL) (Geometric Coefficient of Variation). Phase 1b: 80 mg Galunisertib + Gemcitabine (n=3): 385 (101); Phase 1b: 160 mg Galunisertib + Gemcitabine (n=2): NA (NA) [Not analyzed due to insufficient number of participants with enough PK samples.]; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=3): 1050 (39).

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

Phase 1b: Number of Participants With Tumor Response [Baseline to end of Phase 1b (up to 1 year)]. Number, Participants. Progressive Disease (PD): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=5): 3; Phase 1b: 160 mg Galunisertib + Gemcitabine (n=4): 1; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=5): 2. Stable Disease (SD): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=5): 1; Phase 1b: 160 mg Galunisertib + Gemcitabine (n=4): 2; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=5): 2. Partial Response (PR): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=5): 0; Phase 1b: 160 mg Galunisertib + Gemcitabine (n=4): 1; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=5): 0. Non-Complete Response/Non-Progressive Disease (NC): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=5): 0; Phase 1b: 160 mg Galunisertib + Gemcitabine (n=4): 0; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=5): 1. Not Assessed (NA): Phase 1b: 80 mg Galunisertib + Gemcitabine (n=5): 1; Phase 1b: 160 mg Galunisertib + Gemcitabine (n=4): 0; Phase 1b: 300 mg Galunisertib + Gemcitabine (n=5): 0.

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

Phase 2: Progression Free Survival (PFS) [Baseline to first date of progressive disease or death due to any cause (up to 2 years)]. Median, Months (95% Confidence Interval). Phase 2: 300 mg Galunisertib + Gemcitabine (n=104): 4.11 (2.66 to 5.42); Phase 2: Placebo + Gemcitabine (n=52): 2.86 (1.94 to 3.75).

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

Phase 2: Percentage Change From Baseline in Tumor Size (CTS) [Baseline, end of Cycle 2 (up to 56 days)]. Geometric Mean, Percent change in tumor size (95% Confidence Interval). Independent Assessor 1: Phase 2: 300 mg Galunisertib + Gemcitabine (n=104): 0.95 (0.90 to 1.01); Phase 2: Placebo + Gemcitabine (n=52): 0.92 (0.87 to 0.98). Independent Assessor 2: Phase 2: 300 mg Galunisertib + Gemcitabine (n=104): 1.03 (0.95 to 1.11); Phase 2: Placebo + Gemcitabine (n=52): 0.98 (0.92 to 1.05).

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

Phase 2: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) [Baseline to measured progressive disease (up to 2 years)]. Number, Percentage of Participants (95% Confidence Interval). Phase 2: 300 mg Galunisertib + Gemcitabine (n=104): 10.6 (5.4 to 18.1); Phase 2: Placebo + Gemcitabine (n=52): 3.8 (0.5 to 13.2).

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

Phase 2: Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) [Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)]. Mean, mg*h/L (Inter-Quartile Range). Phase 2: 300 mg Galunisertib + Gemcitabine (n=99): 5.56 (3.82 to 7.91).

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

Phase 2: Population PK: Maximum Concentration (Cmax) of Galunisertib [Cycle 1 Days 14 (predose; 0.5, 2, 3, and 6 hours post dose), 24h (Days 15) and 48h (Days 16)]. Mean, ng/mL (Inter-Quartile Range). Phase 2: 300 mg Galunisertib + Gemcitabine (n=99): 904 (668 to 1194).

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

Phase 2: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) at Study Completion [Baseline, study treatment completion (up to 1 year)]. Mean, Units on a scale (Standard Deviation). Phase 2: 300 mg Galunisertib + Gemcitabine (n=7): 2.54 (2.53); Placebo+Gemcitabine (n=2): 1.50 (2.12).

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

Phase 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA19-9) Level at First Study Completion Follow-up [Baseline, study treatment completion after first follow up visit (up to 1 year)]. Median, Units/Milliliter (U/mL) (Full Range). Phase 2: 300 mg Galunisertib + Gemcitabine (n=38): 32.7 (-93.8 to 3636.3); Phase 2: Placebo + Gemcitabine (n=21): -33.3 (-98.1 to 2460.9).