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)
3 other identifiers
interventional
41
2 countries
9
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2015
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2015
CompletedFirst Submitted
Initial submission to the registry
April 17, 2015
CompletedFirst Posted
Study publicly available on registry
April 22, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 13, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 8, 2020
CompletedResults Posted
Study results publicly available
September 9, 2021
CompletedSeptember 9, 2021
August 1, 2021
4 years
April 17, 2015
July 2, 2021
August 13, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
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).
Cycle 1 through Cycle 2 (Up to 2 Months)
Secondary Outcomes (8)
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
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
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
Phase 2: Progression Free Survival (PFS)
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)
Baseline to Measured Progressive Disease (Up to 35 Months)
- +3 more secondary outcomes
Study Arms (6)
Galunisertib + Nivolumab (Cohort 1) Phase 1b
EXPERIMENTAL50 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.
Galunisertib + Nivolumab (Cohort 2) Phase 1b
EXPERIMENTAL50 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.
Galunisertib + Nivolumab (Cohort 3) Phase 1b
EXPERIMENTAL80 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.
Galunisertib + Nivolumab (Cohort 4) Phase 1b
EXPERIMENTAL150 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.
Galunisertib + Nivolumab - Non-small Cell Lung Cancer (NSCLC) Phase 2
EXPERIMENTAL150 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 - Hepatocellular Carcinoma (HCC) Phase 2
EXPERIMENTAL150 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.
Interventions
Administered orally
Administered IV
Eligibility Criteria
You may qualify if:
- 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.
- +2 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Bristol-Myers Squibbcollaborator
Study Sites (9)
University of Alabama at Birmingham Medical Center
Birmingham, Alabama, 35294, United States
University of California - San Diego
La Jolla, California, 92093, United States
H Lee Moffitt Cancer Center
Tampa, Florida, 33612-9497, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Institut Catala d'Oncologia
Barcelona, 08907, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Regional Universitario de Málaga
Málaga, 29010, Spain
Related Publications (1)
Nadal E, Saleh M, Aix SP, Ochoa-de-Olza M, Patel SP, Antonia S, Zhao Y, Gueorguieva I, Man M, Estrem ST, Liu J, Avsar E, Lin WH, Benhadji KA, Gandhi L, Guba SC, Diaz IA. A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer. BMC Cancer. 2023 Jul 28;23(1):708. doi: 10.1186/s12885-023-11153-1.
PMID: 37507657DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Due low enrollment, the HCC cohort was terminated early.
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
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)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 17, 2015
First Posted
April 22, 2015
Study Start
January 1, 2015
Primary Completion
December 13, 2018
Study Completion
July 8, 2020
Last Updated
September 9, 2021
Results First Posted
September 9, 2021
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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.