Clinical Trial 18537

Cancer Type:
Interventions:BMS-936558 (Nivolumab); Galunisertib; LY2157299 (Galunisertib); Nivolumab

Study Type: Treatment
Phase of Study: Phase I/II

  • Scott Antonia


Study Title

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


The main purpose of this study is to help answer the following research questions: Which dose of galunisertib plus nivolumab is safe to give to participants with advanced solid tumors. Which dose of galunisertib plus nivolumab is safe to give to participants with lung cancer, liver cancer, or brain cancer, who did not respond to previous treatment.


The primary objective of the Phase 1b part of this study is to assess the safety and tolerability of orally dosed galunisertib 14 days on/14 days off in combination with IV nivolumab 3 mg/kg Q2W by identifying dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) or pharmacologically active dose (PAD) of the combination in patients with advanced refractory solid tumours during the first 2 cycles. The primary objective of the Phase 2 part (expansion cohorts) of this study is to assess the safety of the combination of galunisertib and nivolumab in patients with refractory or recurrent NSCLC, HCC, or glioblastoma who have failed 1 prior line of therapy.

Inclusion Criteria

  • Phase 1b: Must have advanced refractory solid tumors in any line of therapy. Phase 2: If fewer than 3 Non-Small Cell Lung Cancer (NSCLC), Hepatocellular Carcinoma (HCC) or Glioblastoma (GB) participants are not included in the Phase 1b, then a safety run-in must occur for any of the cohorts that have fewer than 3 participants in Phase 1.
  • Phase 2, must have 1 of the following tumor types: recurrent or refractory NSCLC (any histology), HCC with elevated alpha-fetoprotein (AFP) ≥200 nanogram/milliliter (ng/mL), or GB (primary).
  • 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, HCC or glioblastoma and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease.
  • NSCLC: 1) 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. 2) 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. 3) Tumors with driver mutations treated with a tyrosine kinase inhibitor or crizotinib are eligible. Participants who have progressed on a tyrosine kinase inhibitor or crizotinib or are intolerant to this targeted therapy must receive platinum-based therapy prior to enrollment in this study. 4) Maintenance or switch maintenance therapy after first-line chemotherapy will be considered part of the first-line regimen and is acceptable. 5) 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 disease within the 6 months before screening would be counted as having received 1 prior platinum-containing regimen and 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.
  • HCC: 1) One prior line of therapy which must include sorafenib or 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. May have had clinical progression only following sorafenib or local therapy. 2) Must have Child-Pugh A only. May have any viral status (hepatitis B, hepatitis C, none). 3) Have a viral load > For Glioblastoma (GB): Previous first line of therapy with at least radiotherapy and temozolomide except for participants with O6-methylguanine-DNA methyltransferase (MGMT) unmethylated newly diagnosed GB. Participants with MGMT unmethylated newly diagnosed GB may have received radiation therapy only.
  • Adequate organ function.
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Use an approved contraceptive method.

  • Exclusion Criteria

  • Have moderate or severe cardiovascular disease: 1) 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. 2) 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). 3) Have major abnormalities documented by Echocardiogram with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction > 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.