Lung cancer is the leading cause of cancer death in both men and women. PD-L1 is upregulated in non-small-cell lung carcinoma ( NSCLC ) and may be associated with a poor prognosis.
MEDI4736 is a human IgG1 antibody which binds specifically to PD-L1 preventing binding to PD-1 and CD80.
An ongoing phase 1, multicenter, open-label study is evaluating the safety and efficacy of MEDI4736 administered IV )( intravenous ) every 2 weeks ( q2w ) or every 3 weeks ( q3w ) using a 3+3 dose escalation followed by expansion cohorts.
NSCLC patients were assigned to expansion cohorts by histology and line of therapy ( including treatment- naïve patients ).
Retreatment was permitted for progression after 12 months of therapy. Response is assessed by immune-related response criteria ( irRC ) in escalation and RECIST v1.1 in expansion.
As of January 17, 2014, 13 NSCLC patients in dose escalation ( median age 65 years; 40-76 ), all performance status ( PS ) 0-1, with a median of 4 prior treatments, received a median of 7 doses ( 1-25 ) of MEDI4736 across 6 cohorts ( 0.1 – 10 mg/kg q2w; 15 mg/kg q3w ).
Treatment-related adverse effects occurred in 43% of patients, all of which were grade 1-2; none led to discontinuation of study drug.
No pneumonitis or colitis was reported in dose escalation.
Of 13 patients, 3 partial responses ( PRs ) were observed, with 2 additional patients achieving tumor shrinkage not meeting partial response per irRC ( 46% and 48% decreases ).
Tumor shrinkage was reported as early as first assessment ( 6 weeks ) and benefit was durable; 4/13 pts remain on study ( 10+, 10+, 11.1+, 14.9+ months ) as of the data cutoff.
Expansion cohorts opened September 2013; 43 patients ( including treatment-naïve patients ) have been dosed, with the opportunity to enroll more than 300 NSCLC patients in total.
Preliminary clinical activity has been observed with acceptable safety, no greater than or equal to grade 3 pneumonitis, and no apparent differences in toxicity between treatment-naïve versus pretreated patients.
Assessment of clinical activity by PD-L1 expression, underlying mutation, smoking history, and line of therapy patient-reported outcomes is ongoing.
In conclusion, the preliminary safety and durable clinical efficacy profile of MEDI4736 in NSCLC supports continued clinical development; adverse reactions are manageable, even in highly pretreated patients.
Recruitment continues and development of MEDI4736 in non-small-cell lung carcinoma as monotherapy and in combination is ongoing. ( Xagena )
Brahmer JR et al, J Clin Oncol 2014; 32:5s ( suppl; abstr 8021 )