Data support rapid progression to Phase III development for MEDI4736 (PD-L1); highlight progress of company’s oncology portfolio
Chicago, Ill., June 3, 2014 -- MedImmune, the global biologics research and development arm of AstraZeneca, presented results today from its novel investigational immunotherapy portfolio, focusing on MEDI4736, at the American Society of Clinical Oncology (ASCO) 2014 Annual Meeting. Overall, studies demonstrated durable clinical activity and tolerability for MEDI4736 across a range of tumor types.
This announcement follows the recent progression of the first Phase III study for MEDI4736, an investigational, engineered, human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. It is believed that by targeting PD-L1, MEDI4736 may block this ligand from sending out signals to T-cells to ‘ignore’ tumor cells, thereby countering cancer’s immune-evading tactics.
Multiple sets of data were presented from MEDI4736, including dose-escalation data, dose expansion data, and an analysis of pharmacokinetic data.
MEDI4736: Four Data Sets Point to Early Clinical Activity and Tolerability
In a Phase I dose-escalation study (Study 1108) of MEDI4736 in 27 patients with advanced solid tumors, reduction of tumor burden was seen at multiple dose levels in as early as six weeks. Clinical activity was maintained for at least one year, with 19 percent of patients achieving a partial response and 39 percent of patients achieving disease control. There was a very low frequency of drug-related serious adverse events, and no dose-limiting toxicities were observed. The tumor types included in the escalation phase of this study were non-small cell lung cancer (NSCLC), melanoma, colorectal cancer and renal cell cancer (Lutzky, abstract 3001).
Treated patients who had advanced NSCLC were separately reported in a poster discussion at ASCO. Data from ~150 NSCLC patients found no treatment discontinuations for toxicity, drug-related colitis of any grade, or grade three or four pulmonary toxicities. An early signal of clinical activity was observed in patients with both squamous and non-squamous NSCLC treated with MEDI4736 (Brahmer, 8021).
Data from the dose expansion phase in ~350 patients provided further information on the clinical activity and tolerability profile of MEDI4736, showing early evidence of clinical activity in multiple tumor types, including NSCLC, squamous cell carcinoma of the head and neck (SCCHN), pancreatic cancer, gastroesophageal cancer, and cutaneous melanoma (Segal, abstract 3002).
Additionally, an analysis of pharmacokinetic (PK) / pharmacodynamics (PD) data indicated a very low incidence of immunogenicity (2 of 196 patients) with no impact on PK or PD at the phase II and III dose of 10 mg/kg. Furthermore, the study demonstrated dose-dependent PK and soluble PD-L1 suppression in patients with solid tumors (Fairman, abstract 2602).
“The data presented at ASCO reinforce the importance MEDI4736 plays in our immuno-oncology portfolio, and more broadly, the potential role it has to help in transforming cancer therapy, alone and in combination with other treatments,” said Dr. Edward Bradley, Senior Vice President, R&D and Oncology iMED Head, MedImmune. “In our Phase I studies, MEDI4736 has demonstrated encouraging clinical activity and tolerability profile across a range of tumor types. We look forward to seeing further data on this molecule as part of current Phase III program, as well as the numerous combination trials underway.”
Accelerated development of Novel Combinations, Additional Immunotherapy Studies
There are two ongoing combination studies exploring different doses and schedules of tremelimumab (CTLA-4) + MEDI4736, one in multiple tumor types through a collaboration with the Cancer Research Institute/Ludwig Cancer Research and the other in NSCLC. MedImmune provided a preliminary status update of the Phase I MEDI4736 + tremelimumab combination study in NSCLC at the AstraZeneca analyst and investor briefing on June 2, 2014 at ASCO. Dose escalation is continuing with no maximum tolerated dose defined to date. Early, preliminary clinical activity has been observed with this combination in patients with advanced NSCLC.
MEDI4736 and tremelimumab target non-redundant pathways to fight cancer, working at different checkpoints to engage the immune system to possibly overcome cancer’s immune-evading tactics. In one mouse study, combining agents that target PD-L1 and CTLA-4 produced synergistic effects and led to complete tumor regression.
MedImmune is also exploring tremelimumab as monotherapy in a pivotal study for malignant mesothelioma, a patient population with a very high unmet need. Updated Phase II data from an investigator-initiated trial exploring tremelimumab in malignant mesothelioma was also presented at ASCO.
MedImmune data at ASCO 2014 continue to highlight the company’s immunotherapy portfolio. Among the 10 abstracts presented by MedImmune, data include:
- Combination therapies: recruitment is ongoing for additional combination treatments. This includes a Phase I study of MEDI4736 in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma (Gordon, abstract TPS9108).
- MEDI3617: a Phase I dose-escalation study investigated MEDI3617 alone and in combination with carboplatin/paclitaxel, paclitaxel or bevacizumab across a variety of tumor types in adults with advanced solid tumors, and researchers observed clinical activity along with an acceptable tolerability profile (Hyman, abstract 3012).
- MEDI-551: a Phase II study is ongoing to evaluate tolerability of MEDI-551 among 124 patients with relapsed/refractory chronic lymphocytic leukemia (Gladstone, abstract 3028).
NOTES TO EDITORS
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centers. For more information, please visit www.medimmune.com.
Tracy Rossin, MedImmune