Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Hepatocellular

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Mitogens

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

50 milligrams (mg) Galunisertib administered orally once daily (QD) on Day 1 through Day 14 of each 4-week cycle in combination with 3 milligrams per kilogram (3 mg/kg) nivolumab given intravenously (IV), every 2 weeks (Q2W), (Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met.

50 mg Galunisertib administered orally twice daily (BID) on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W,(Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met.

80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met.

150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W,(Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met.

150 mg Galunisertib administered orally BID for the first 14 days of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

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).

A Study of Galunisertib (LY2157299) in Combination With Nivolumab in Advanced Refractory Solid Tumors and in Recurrent or Refractory NSCLC, or Hepatocellular Carcinoma

A Phase 1b/2 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of a Novel Transforming Growth Factor-beta Receptor I Kinase Inhibitor (Galunisertib) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors (Phase 1b) and in Recurrent or Refractory Non-small Cell Lung Cancer or Hepatocellular Carcinoma (Phase 2)

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

The MTD is defined as the highest tested dose that has less than 33% probability of causing a dose limiting toxicity (DLT).

Minimum Concentration (Cmin) of Nivolumab

Area under the plasma concentration curve from time zero to 24 hours of galunisertib for Cycle 1 and Cycle 2.

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).

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.

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.

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 to response was measured from the date of first study treatment to the first documented response of Complete Response (CR) or Partial Response (PR).

Overall Survival was determined from the date of first study treatment until death due to any cause.

Bristol-Myers Squibb

Eli Lilly and Company

All participants who received at least one dose of study drug.

50 mg Galunisertib administered orally QD on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV every Q2W on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib + Nivolumab (Cohort 1) Phase 1b

50 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib + Nivolumab (Cohort 2) Phase 1b

80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib + Nivolumab (Cohort 3) Phase 1b

150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib + Nivolumab (Cohort 4) Phase 1b

150 mg Galunisertib administered orally BID for the first 14 days of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met.

Galunisertib + Nivolumab (NSCLC) Phase 2

Galunisertib + Nivolumab (HCC) Phase 2

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.

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.

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.

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.

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.

Galunisertib + Nivolumab - Non Small Cell Lung Cancer (NSCLC) Phase 2

Galunisertib + Nivolumab - Hepatocellular Carcinoma(HCC) Phase 2

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Spain

Region of Enrollment

Due low enrollment, the HCC cohort was terminated early.

Chief Medical Officer

Cohort 1: 50 mg Galunisertib administered QD on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, every Q2W, on Day 1 and Day 15 for 2 cycles.

Cohort 2: 50 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

Cohort 3: 80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

Cohort 4: 150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

Phase 1b Participants

All participants who received at least one dose of study drug in Phase 1b per protocol.

Phase 1b: Maximum Tolerated Dose (MTD) of Galunisertib in Combination With Nivolumab

50 mg Galunisertib administered orally QD on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV every Q2W on Day 1 and Day 15 for 2 cycles.

50 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W on Day 1 and Day 15 for 2 cycles.

Galunisertib + Nivolumab ( HCC) Phase 2

All participants who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Nivolumab

50 mg Galunisertib administered orally QD on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

50 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV Q2W (Day 1 and Day 15) for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

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

All participants who received at least one dose of study drug and were evaluable for TE ADA.

Number of Participants With Anti-Nivolumab Antibodies When Administered in Combination With Galunisertib

All participants who received at least one dose of study drug in the Phase 2 cohorts. Censored participants Galunisertib + Nivolumab (NSCLC) Phase 2 = 6.

Phase 2: Progression Free Survival (PFS)

All participants who received at least one dose of study drug in Phase 2 cohorts.

Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response: Objective Response Rate (ORR)

150 mg Galunisertib administered orally BID 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.

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.

Phase 2: Duration of Response (DoR)

All participants who received at least one dose of study drug in Phase 2 cohorts and had a documented response of CR or PR.

Phase 2: Time to Response

All participants who received at least one dose of study drug in Phase 2 cohorts. Censored participants Galunisertib + Nivolumab (NSCLC) Phase 2 = 8.

Phase 2: Overall Survival (OS)

50 milligram (mg) Galunisertib administered orally daily (QD) on Day 1 through Day 14 of each 4-week cycle in combination with 3 milligrams per kilogram (3 mg/kg) nivolumab given intravenously (IV), every 2 weeks (Q2W), on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

50 mg Galunisertib administered orally twice daily (BID) on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, on Day 1 and Day 15 for 2 cycles. Participants may continue to receive study drug until discontinuation criteria are met.

150 mg Galunisertib administered orally BID for the first 14 days of each 4 week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met.

Spots Global Cancer Trial Database for A Study of Galunisertib (LY2157299) in Combination With Nivolumab in Advanced Refractory Solid Tumors and in Recurrent or Refractory NSCLC, or Hepatocellular Carcinoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial