Development of MEDI4736, an anti-programmed cell death ligand 1 (PD-L1) antibody, as monotherapy or in combination with other therapies in the treatment of non-small cell lung cancer (NSCLC)

Results NCT01693562: As of May 2014, NSCLC cohort included 155 patients (pts) (median age 65 years [3385], PS 0/1/unknown [25%/73%/2%], median 3 [0-7] prior treatments). Median follow-up: 6 weeks (range 067). Treatment-related adverse events (TRAEs): 29% (Grade [Gr] ≥3: 3%); none led to treatment discontinuation. Most frequent TRAEs: fatigue (7%), nausea (5%), and vomiting (5%). No treatment-related colitis any Gr. No treatment-related Gr 3/4 pneumonitis or dyspnea. 58 pts had ≥12 weeks follow-up: 16% had partial response (as early as 6 weeks), duration of response ranged 5-54+ weeks, disease control rate 35%. PD-L1 positivity appears to enrich for response. NCT02000947: As of April, 2014, 12 pts treated at 4 dose-levels (PS 0-1, median 3 [2-5] prior treatments). No DLTs observed in any cohort during DLT observation period. Most frequent TRAEs: -↑amylase, abdominal pain, arthralgia, colitis, diarrhea, epigastric discomfort, fatigue and nausea. TRAEs ≥Gr 3 noted in 3 pts: Gr 3 ↑AST/ ALT & Gr 5 myasthenia (MG) (n = 1), Gr 3 diarrhea/colitis (n = 1), Gr 4 ↑amylase (n = 1). TRAEs led to discontinuation in two subjects: Gr 5 MG and Gr3 colitis. In 12 response-evaluable pts (Figure 1), tumor shrinkage at 8 weeks: 0/3 pts cohort 1a; 6/9 pts cohorts 2a and 3a/b; disease control: 7/12 pts. Dose-escalation ongoing; total of 6 dose-levels, including cohort 5a (MEDI4736/Treme: 15/10 mg/kg), has been cleared since cut-off.