AstraZeneca Reports Top-Line Result of Tremelimumab Monotherapy Trial in Mesothelioma

“AstraZeneca and MedImmune, its global biologics research and development arm, today announced that DETERMINE, the Phase IIb clinical trial of 10 mg/kg tremelimumab monotherapy in second or third-line treatment of unresectable malignant mesothelioma, did not meet its primary endpoint of overall survival.

“Robert Iannone, Senior Vice President, Head of Immuno-Oncology, Global Medicines Development at AstraZeneca, said: ‘We are disappointed that tremelimumab monotherapy did not demonstrate a survival benefit in this patient population with no approved medicines beyond first-line treatment. However, we remain confident in tremelimumab’s clinical activity in combination, as shown in our recently published Study 006 trial of tremelimumab and durvalumab in non-small cell lung cancer.’ ”


AZ Cancer Immunotherapy Combo Impresses in Lung Cancer Trial

“Two immuno-oncology drugs in development at AstraZeneca (AZ) have shown potential as a dual therapy for non-small cell lung cancer, according to a new study.

“The phase II trial – reported in Lancet Oncology – found that combining anti-PD-L1 antibody durvalumab with anti-CTLA-4 antibody tremelimumab achieved an overall response rate (ORR) of 23%, significantly higher than has previously been seen with durvalumab alone in this setting.

“The trial was small and focused primarily on safety, but the preliminary efficacy signal – albeit in just 26 patients – is encouraging, according to an editorial accompanying the study by Edward Garon of the David Geffen School of Medicine at the University of California, Los Angeles.”


Durvalumab/Tremelimumab Combo Could Be Useful in First-Line Treatment for NSCLC

“A combination of the anti–PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) with the anti–CTLA-4 monoclonal antibody tremelimumab showed improved tumor response in patients with advanced non–small cell lung cancer (NSCLC) over single-agent therapy.

“The study, published in the Journal for ImmunoTherapy of Cancer, was a phase I, open-label, dose-escalation/expansion study that contained 84 patients. Of these patients, 48 had two or more prior lines of therapy. Data from the study showed improved tumor response regardless of PD-L1 status, with an overall response rate of 25% and 35% of PD-L1-negative patients receiving a response (0% tumor cell staining).”


Anti-PD-1 Agents Superior to Others in Advanced Melanoma

“Immunotherapy targeting the programmed cell death (PD) pathway was associated with better outcomes in patients with metastatic melanoma than any other therapy, a new meta-analysis concludes.

“The meta-analysis was featured in a poster presentation here at the Society for Melanoma Research 2015 Congress.

“Anti-PD-1 agents might be a better choice as a first-line therapeutic option, according to Seongseok Yun, MD, PhD, an internal medicine resident at the University of Arizona Medical Center in Tucson, and Nicole Vincelette, a PhD student from the Mayo Clinic in Rochester, Minnesota.”


AstraZeneca and MedImmune Present Positive Immuno-Oncology Combination Data at ASCO 2015

“AstraZeneca AZN, -0.75% and MedImmune, AstraZeneca’s global biologics research and development arm, today presented encouraging results from their novel combination-focused immuno-oncology portfolio at the American Society of Clinical Oncology (ASCO) Annual Meeting 2015.

“Overall, data indicated clinical activity with manageable safety profiles for the anti-programmed cell death ligand 1 (PD-L1) monoclonal antibody MEDI4736, both as monotherapy and in combination with other immuno-oncology and small molecule therapies across different tumor types and tumor biology.

“MEDI4736 and tremelimumab combination shows clinical activity and tolerability in both PD-L1 positive and PD-L1 negative advanced non-small cell lung cancer (NSCLC) patients; dose confirmed for future studies

“Results from the combination study of MEDI4736 and tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody, in the treatment of advanced NSCLC, demonstrated clinical activity in heavily-pretreated patients with a manageable safety profile, establishing appropriate doses to move forward into Phase III combination trials.”


AstraZeneca Drug Combination on Track to Fight Lung Cancer

“A closely watched immune system-boosting drug cocktail from Britain’s AstraZeneca shows promise in advanced lung cancer, despite adverse side effects in a number of patients.

“Researchers said on Wednesday that the combination of the experimental drugs MEDI4736 and tremelimumab had ‘a manageable safety profile with evidence of clinical activity, including in PD-L1 negative disease’.

“The update was provided in a scientific summary, or abstract, released ahead of the annual meeting of the American Society of Clinical Oncology (ASCO) later this month.

“MEDI4736 is an anti-PD-L1 therapy, which works by stopping a tumor’s ability to evade the body’s defenses. Tremelimumab blocks a different molecule, CTLA-4, that also keeps the immune system from attacking cancer.”


Immune Checkpoint Inhibitors in Melanoma: New Directions


The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…


New Combo of Immunotherapy Drugs Is Safe, Shrinks Tumors in Metastatic Melanoma Patients

“Once again, researchers at Penn’s Abramson Cancer Center have extended the reach of the immune system in the fight against metastatic melanoma, this time by combining the checkpoint inhibitor tremelimumab with an anti-CD40 monoclonal antibody drug. The first-of-its-kind study found the dual treatments to be safe and elicit a clinical response in patients, according to new results from a phase I trial to be presented at the AACR Annual Meeting 2015 on Sunday, April 19.

“Researchers include first author David L. Bajor, MD, instructor of Medicine in the division of Hematology/Oncology, and senior author Robert H. Vonderheide, MD, DPhil the Hanna Wise Professor in Cancer Research.

” ‘We’ve had wonderful success with immunotherapies, but we are barely scratching the surface,’ Bajor said. ‘Checkpoint inhibitors are just the beginning. When they are thoughtfully combined with immune-stimulating compounds like CD40 or drugs targeting other facets of the immune system we hope to be able to increase the response rate to previously approved therapies.’

“Known as a checkpoint inhibitor, tremelimumab is an investigational monoclonal antibody that ‘cuts the brakes’ of the immune system by targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), a protein that can switch off a patient’s immune response. Anti-CD40 drugs (in this trial, CP- 870,893) antagonize the CD40 receptor, and effectively ‘push the gas’ on the immune system to make it work harder.”


Tremelimumab Granted Orphan Drug Designation by US FDA for Treatment of Malignant Mesothelioma

“AstraZeneca today announced that the US Food and Drug Administration has granted Orphan Drug Designation for the anti-CTLA-4 monoclonal antibody, tremelimumab, for the treatment of malignant mesothelioma.

“Mesothelioma is a rare, aggressive cancer that most often affects the lining of the lungs and abdomen. Available treatments for mesothelioma are very limited, particularly for patients with advanced disease.

“ ‘There is a significant need for new treatment options for patients with mesothelioma because fewer than five percent of patients currently survive beyond five years, even when they receive timely diagnosis and care. Our aim is to rapidly advance the development of tremelimumab as a potential new treatment option for these patients,’ said Robert Iannone, Senior Vice President, Head of Immuno-oncology, Global Medicines Development at AstraZeneca.

“The Orphan Drug Designation programme provides orphan status to drugs and biologics, which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US1.”