Bristol-Myers Squibb Presents Ipilimumab Phase 2 Results

Ipilimumab is a T-cell potentiator that specifically blocks the inhibitory signal of CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. Suppression of CTLA-4 can augment the immune system’s T-cell response in fighting disease.

According to the Bristol-Myers Squibb, the study, known as 041, met the predefined criteria for significant improvement (p-value of <0.1) in immune-related progression –free survival (irPFS), the primary endpoint, over chemotherapy alone.

An additional analysis of progression-free survival (PFS), assessed using traditional mWHO criteria1, also reached statistical significance in one of the two dosing schedules that combined ipilimumab with standard chemotherapy.

The 041 study evaluated two distinct regimens of ipilimumab in combination with a chemotherapy regimen that is commonly used to treat advanced NSCLC in the first-line setting compared to the same chemotherapy regimen given alone.

The ipilimumab arms improved irPFS by approximately one month compared to the chemotherapy-only arm. Immune-related adverse events reported in the study included gastrointestinal, skin, liver, or endocrine systems. Moreover, the planning for a Phase 3 study of ipilimumab in the treatment of NSCLC is under way.

Study 041 is a multi-center, randomized, double blind, three arm trial evaluating the efficacy and safety of ipilimumab in combination with paclitaxel/carboplatin compared to paclitaxel/carboplatin alone in previously-untreated patients with Stage IIIb or IV non-small cell lung cancer (n=203).

The trial enrolled patients with squamous and non-squamous cell histology. Patients were randomized to receive ipilimumab (10 mg/kg every three weeks) concurrent with the first four cycles of chemotherapy (concurrent regimen), ipilimumab (10 mg/kg every three weeks) in combination with cycles three through six of chemotherapy (phased or sequential regimen) or chemotherapy alone.

Ipilimumab was administered in a maintenance schedule (10 mg/kg every 3 months) after discontinuation of chemotherapy and until progression or undue toxicity in the former two treatment arms.

Thomas Lynch, director of Yale Cancer Center and physician-in-chief of the Smilow Cancer Hospital at Yale-New Haven, said: “Results from this Phase 2 study are very encouraging and support further investigation of ipilimumab in NSCLC in large scale Phase 3 trials. As with melanoma, ipilimumab brings an innovative approach to lung cancer, which is very difficult to treat. These results add to our understanding of the potential of immuno-oncology in the treatment of cancer.”