Solid Tumor, Non-Small Cell Lung Cancer Recurrent, Hepatocellular Carcinoma Recurrent
Conditions
Brief summary
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).
Interventions
DRUGGalunisertib
Administered orally
DRUGNivolumab
Administered IV
Sponsors
Bristol-Myers Squibb
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Phase 1b, must have advanced refractory solid tumors in any line of therapy. * For Phase 2, must have one of the following tumor types: recurrent or refractory NSCLC (any histology), or HCC with elevated alpha-fetoprotein (AFP) ≥200 nanogram/milliliter (ng/mL). * For Phase 2 only, have had disease progression or be refractory or intolerant to 1 prior line of therapy (first line therapy) for recurrent or refractory for NSCLC or HCC and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease. This may include multiple chemotherapeutic, targeted or immunotherapeutic agents with or without radiation therapy and/or surgery. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within the same drug class (eg, cisplatinum to carboplatinum) within a regimen in order to manage toxicity does not define the start of a new line of therapy. * For NSCLC: * Prior lines of therapy must include a platinum-based therapy. Investigational agents used in combination with standard therapies are allowed. Participants who received platinum-based neoadjuvant or adjuvant therapy and subsequently received platinum-based therapy as first-line therapy are eligible. * Participants who have completed neo-adjuvant or adjuvant therapy with a platinum doublet and have experienced disease recurrence within 6 months of completing the platinum doublet are eligible. * Tumors with driver mutations (epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive) treated with a tyrosine kinase inhibitor or crizotinib are eligible. For participants who have progressed on a tyrosine kinase inhibitor or crizotinib or are intolerant to this targeted therapy, that participant must receive platinum-based therapy prior to enrollment in this study. Documentation of such mutations must be available and entered into the electronic case report form (eCRF). * Maintenance or switch maintenance therapy after first-line chemotherapy will be considered part of the first-line regimen and is acceptable. Participants who completed and progressed on a platinum-containing regimen as adjuvant, neoadjuvant, or part of a course of chemoradiation therapy given from locally advanced disease and developed recurrent (local or metastatic) disease within the 6 months before screening would be counted as having received 1 prior platinum-containing regimen and therefore would not require re-treatment with a platinum-containing regimen for Stage IIIB, IV, or recurrent disease and are eligible. However, participants must have received at least 2 cycles of a platinum doublet based chemotherapy before discontinuation for toxicity. If participants received only one cycle of a platinum doublet and discontinue due to clear progression, that regimen should be counted as a prior line of therapy. * For HCC: * One prior line of therapy which must include sorafenib or participant must have progressed or been intolerant to sorafenib for participants not eligible for transarterial chemoembolization. Participants who had sorafenib for locally advanced disease or are intolerant to sorafenib are eligible. Participants may have had clinical progression only following sorafenib or local therapy. * Must have Child-Pugh A only. Participants may have any viral status (hepatitis B, hepatitis C, or none). * Have a viral load \<100 international units/milliliter (IU/mL). * For hepatitis B participants, must be on a nucleoside analog reverse transcriptase inhibitor (lamivudine, telbivudine, adefovir, tenofovir, or entecavir). * Have adequate organ function. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Use an approved contraceptive method.
Exclusion criteria
* For Phase 2 only, more than 1 prior line of therapy for their tumor type. * Have moderate or severe cardiovascular disease: * Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension. * Have documented major electrocardiogram (ECG) abnormalities which are clinically significant at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle-branch blocks, ventricular hypertrophy, or recent myocardial infarction). * Have major abnormalities documented by ECHO with Doppler: * Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation. * Left ventricular (LV) ejection fraction \<50%, evaluation based on the institutional lower limit of normal. * Have septal aneurysm or other heart aneurysm. * Any aneurysm of the major vessels. * Active infection with hepatitis B virus (HBV) (positive hepatitis B surface antigen); HCV is allowed only in HCC participants. HCC participants at risk for HBV reactivation (as defined by anti-hepatitis B core antibody positive) are only eligible in the HCC cohort. * Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Maximum Tolerated Dose (MTD) of Galunisertib in Combination With Nivolumab | Cycle 1 through Cycle 2 (Up to 2 Months) | The MTD is defined as the highest tested dose that has less than 33% probability of causing a dose limiting toxicity (DLT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 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 | Area under the plasma concentration curve from time zero to 24 hours of galunisertib for Cycle 1 and Cycle 2. |
| Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | Cycle 1: Days 1, 14, 15 Predose and Day 100 Follow-up; Cycles 2 and 4: Day 1 Predose and Day 100 Follow-up | 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). |
| Phase 2: Progression Free Survival (PFS) | Date of First Study Treatment to Measured Progressive Disease or Death (Up to 35 Months) | 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. |
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | PK: Cycle 1 Day 15 Predose; Cycle 2: Day 1: Pre-dose; Day 15: Predose: Cycle 4: Day 1: Predose | Minimum Concentration (Cmin) of Nivolumab |
| Phase 2: Duration of Response (DoR) | 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) | 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. |
| Phase 2: Time to Response | Date of First Study Treatment to Date of Complete Response or Partial Response (Up to 35 Months) | 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). |
| Phase 2: Overall Survival (OS) | Date of First Study Treatment to Death from Any Cause (Up to 35 Months) | Overall Survival was determined from the date of first study treatment until death due to any cause. |
| Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response: Objective Response Rate (ORR) | Baseline to Measured Progressive Disease (Up to 35 Months) | 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. |
Countries
Spain, United States
Participant flow
Recruitment details
Due low enrollment, the Hepatocellular Carcinoma (HCC) cohort was terminated early.
Pre-assignment details
Participants who had at least one post baseline tumor assessment were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Galunisertib + Nivolumab (Cohort 1) Phase 1b 50 mg Galunisertib administered orally daily on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given intravenously (IV) every 2 weeks (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met. | 3 |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b 50 mg Galunisertib administered orally twice daily on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV every 2 weeks (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met. | 5 |
| Galunisertib + Nivolumab (Cohort 3) Phase 1b 80 mg Galunisertib administered orally twice daily on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV every 2 weeks(Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met. | 3 |
| Galunisertib + Nivolumab (Cohort 4) Phase 1b 150 mg Galunisertib administered orally twice daily on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV every 2 weeks (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met. | 4 |
| Galunisertib + Nivolumab - Non Small Cell Lung Cancer (NSCLC) Phase 2 150 mg Galunisertib given orally twice daily for the first 14 days of each 4 week cycle in combination with 3 mg/kg nivolumab given IV every 2 weeks (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met. | 25 |
| Galunisertib + Nivolumab - Hepatocellular Carcinoma(HCC) Phase 2 150 mg Galunisertib given orally twice daily for the first 14 days of each 4 week cycle in combination with 3 mg/kg nivolumab given IV every 2 weeks (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met. | 1 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Galunisertib + Nivolumab (Cohort 1) Phase 1b | Galunisertib + Nivolumab (Cohort 2) Phase 1b | Galunisertib + Nivolumab (Cohort 3) Phase 1b | Galunisertib + Nivolumab (Cohort 4) Phase 1b | Galunisertib + Nivolumab - Non Small Cell Lung Cancer (NSCLC) Phase 2 | Galunisertib + Nivolumab - Hepatocellular Carcinoma(HCC) Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 15.6 | 47.2 years STANDARD_DEVIATION 15.8 | 36.0 years STANDARD_DEVIATION 5.3 | 61.5 years STANDARD_DEVIATION 9 | 61.0 years STANDARD_DEVIATION 8.4 | 64.0 years | 57.6 years STANDARD_DEVIATION 12.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 25 Participants | 1 Participants | 39 Participants |
| Region of Enrollment Spain | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 24 Participants | 1 Participants | 28 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 9 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 1 Participants | 16 Participants | 0 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 4 / 5 | 1 / 3 | 3 / 4 | 17 / 25 | 1 / 1 |
| other Total, other adverse events | 3 / 3 | 4 / 5 | 3 / 3 | 4 / 4 | 23 / 25 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 2 / 5 | 1 / 3 | 2 / 4 | 13 / 25 | 0 / 1 |
Outcome results
Primary
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)
Population: All participants who received at least one dose of study drug in Phase 1b per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Participants | Phase 1b: Maximum Tolerated Dose (MTD) of Galunisertib in Combination With Nivolumab | 300 milligrams (mg) |
Secondary
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
Population: All participants who received at least one dose of study drug and were evaluable for TE ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Participants | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
| Galunisertib + Nivolumab (Cohort 3) Phase 1b | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
| Galunisertib + Nivolumab (Cohort 4) Phase 1b | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
| Galunisertib + Nivolumab (NSCLC) Phase 2 | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
| Galunisertib + Nivolumab ( HCC) Phase 2 | Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib | 0 Participants |
Secondary
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
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1b Participants | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | 33.5 micrograms per milliliter (µg/mL) |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | 36.2 micrograms per milliliter (µg/mL) |
| Galunisertib + Nivolumab (Cohort 3) Phase 1b | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | 43.2 micrograms per milliliter (µg/mL) |
| Galunisertib + Nivolumab (Cohort 4) Phase 1b | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | 29.2 micrograms per milliliter (µg/mL) |
| Galunisertib + Nivolumab (NSCLC) Phase 2 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab | 37.6 micrograms per milliliter (µg/mL) |
Secondary
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)
Population: All participants who received at least one dose of study drug in Phase 2 cohorts and had a response of complete response or partial response. Censored participants Galunisertib + Nivolumab (NSCLC) Phase 2 = 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Participants | Phase 2: Duration of Response (DoR) | 9.03 months |
Secondary
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)
Population: All participants who received at least one dose of study drug in Phase 2 cohorts. Censored participants Galunisertib + Nivolumab (NSCLC) Phase 2 = 8.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Participants | Phase 2: Overall Survival (OS) | 11.99 months |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | Phase 2: Overall Survival (OS) | 14.52 months |
Secondary
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)
Population: All participants who received at least one dose of study drug in Phase 2 cohorts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b Participants | Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response: Objective Response Rate (ORR) | 24.0 Percentage of Participants |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response: Objective Response Rate (ORR) | 0 Percentage of Participants |
Secondary
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)
Population: All participants who received at least one dose of study drug in the Phase 2 cohorts. Censored participants Galunisertib + Nivolumab (NSCLC) Phase 2 = 6.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Participants | Phase 2: Progression Free Survival (PFS) | 5.26 months |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | Phase 2: Progression Free Survival (PFS) | 5.39 months |
Secondary
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)
Population: All participants who received at least one dose of study drug in Phase 2 cohorts and had a documented response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Participants | Phase 2: Time to Response | 4.2 months |
Secondary
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
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b Participants | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 3060 micrograms*hour per liter (μg*h/L) | Geometric Coefficient of Variation 41 |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 2350 micrograms*hour per liter (μg*h/L) | Geometric Coefficient of Variation 46 |
| Galunisertib + Nivolumab (Cohort 3) Phase 1b | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 2220 micrograms*hour per liter (μg*h/L) | Geometric Coefficient of Variation 164 |
| Galunisertib + Nivolumab (Cohort 4) Phase 1b | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 5580 micrograms*hour per liter (μg*h/L) | Geometric Coefficient of Variation 61 |
| Galunisertib + Nivolumab (NSCLC) Phase 2 | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | 7322 micrograms*hour per liter (μg*h/L) | Geometric Coefficient of Variation 67 |
| Galunisertib + Nivolumab ( HCC) Phase 2 | PK: Area Under the Plasma Concentration -Time Curve of Galunisertib From Time Zero to 24 Hours (AUC [0-24h]) at Steady State | NA micrograms*hour per liter (μg*h/L) | — |