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)
© Brahmer et al.; licensee BioMed Central Ltd. 2014
Published: 6 November 2014
MEDI4736 is an engineered human IgG1 that blocks PD-L1 binding to PD-1 and allows T-cells to recognize and kill tumor. MEDI4736 has single-agent activity and potential for further increased activity in combination. A comprehensive development programme is underway in NSCLC, as monotherapy and in combination.
NSCLC data from 2 multicentre, open-label Phase I studies are reported. NCT01693562 evaluates safety and efficacy of MEDI4736 administered every 2 or 3 weeks. NCT02000947 evaluates safety and efficacy of MEDI4736 in combination with tremelimumab, a human IgG2 anti-CTLA-4 mAb, at 4-week intervals.
NCT01693562: As of May 2014, NSCLC cohort included 155 patients (pts) (median age 65 years [33-85], PS 0/1/unknown [25%/73%/2%], median 3 [0-7] prior treatments). Median follow-up: 6 weeks (range 0-67). 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.
Current safety profile and encouraging early antitumor activity (monotherapy and combination) support continued development in NSCLC. Additional monotherapy NSCLC studies: Phase II 'ATLANTIC' (NCT02087423), Phase III 'PACIFIC' following chemo-radiotherapy (NCT02125461), Combination: Phase I + gefitinib (NCT02088112), and Phase Ib + AZD9291 (NCT02143466). Monotherapy and combination: Phase III 'ARCTIC' vs standard-of-care.
Writing support-Isobel Lever/Ashfield Communications, funding-AstraZeneca
Trial registration NIH
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