The main purpose of this study is to evaluate the safety, tolerability, and efficacy of the study drug known as galunisertib in combination with nivolumab in participants with advanced refractory solid tumors and in recurrent or refractory non-small cell lung cancer (NSCLC) or hepatocellular carcinoma (HCC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Administered orally
Administered IV
University of Alabama at Birmingham Medical Center
Birmingham, Alabama, United States
University of California - San Diego
La Jolla, California, United States
H Lee Moffitt Cancer Center
Tampa, Florida, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Hospital Universitari Vall d'Hebron
Barcelona, Spain
Institut Catala d'Oncologia
Barcelona, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Regional Universitario de Málaga
Málaga, Spain
Phase 1b: Maximum Tolerated Dose (MTD) of Galunisertib in Combination With Nivolumab
The MTD is defined as the highest tested dose that has less than 33% probability of causing a dose limiting toxicity (DLT).
Time frame: Cycle 1 through Cycle 2 (Up to 2 Months)
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab
Minimum Concentration (Cmin) of Nivolumab
Time frame: PK: Cycle 1 Day 15 Predose; Cycle 2: Day 1: Pre-dose; Day 15: Predose: Cycle 4: Day 1: Predose
PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State
Area under the plasma concentration curve from time zero to 24 hours of galunisertib for Cycle 1 and Cycle 2.
Time frame: PK: Cycle 1 and Cycle 2 Day 1: Predose, 0.5 - 3 hours postdose, Cycle 1 and Cycle 2 Day 14: Predose, 0.5 - 2, 3.5 - 5, and 24 hours postdose through Cycle 4 Day 1 predose
Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib
Participants with treatment-emergent anti-nivolumab antibodies when administered with galunisertib were participants with a 4-fold or greater increase in titer from baseline measurement (treatment-boosted). If baseline result is ADA not present, then the subject is TE ADA+, if there is at least 1 postbaseline result of ADA present with titer ≥ 40 (treatment-induced).
Time frame: Cycle 1: Days 1, 14, 15 Predose and Day 100 Follow-up; Cycles 2 and 4: Day 1 Predose and Day 100 Follow-up
Phase 2: Progression Free Survival (PFS)
PFS was defined as the time from the date of first study treatment to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Time frame: Date of First Study Treatment to Measured Progressive Disease or Death (Up to 35 Months)
Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response: Objective Response Rate (ORR)
Objective Response Rate was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time frame: Baseline to Measured Progressive Disease (Up to 35 Months)
Phase 2: Duration of Response (DoR)
Duration of response was measured from the date of documented response to the date of first progression of disease or the date of death due to any cause, whichever is earlier.
Time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 35 Months)
Phase 2: Time to Response
Time to response was measured from the date of first study treatment to the first documented response of Complete Response (CR) or Partial Response (PR).
Time frame: Date of First Study Treatment to Date of Complete Response or Partial Response (Up to 35 Months)
Phase 2: Overall Survival (OS)
Overall Survival was determined from the date of first study treatment until death due to any cause.
Time frame: Date of First Study Treatment to Death from Any Cause (Up to 35 Months)
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