FDA Orphan Designated Drug for Mesothelioma In Trial With Combination Therapy To Assess Increased Efficacy

In April, Mesothelioma Help announced the FDA granted Orphan Drug Designation for tremelimumab for the treatment of malignant mesothelioma. The drug was found to increase survival in mesothelioma patients. Now, in a new clinical trial researchers are assessing whether the combination of tremelimumab and durvalumab for lung cancer treatment will fight the cancer better than either drug alone.

AstraZeneca’s tremelimubab, an immunotherapy drug that targets the T Cell receptor protein cytotoxic T-lymphocyte-associated protein 4 (CTLA4), belongs to a class of drugs that are known as “immune checkpoint inhibitors.” Durvalumab, also from AstraZeneca, is an investigational immunotherapy drug (also referred to as MEDI4736 ) that targets the PD-L1 protein. The drug works by blocking signals from PD-L1 tumors, activating the immune system, allowing it to take over and attack and kill cancer cells.

In results posted of the Phase 1B clinical trial in the Feb. 5 issue of The Lancet Oncology, researchers report that the combination showed a “manageable tolerability” and induced a response rate of 23% in patients irrespective of PD-L1 status. This indicates that even patients without the PD-L1 protein may benefit from the combination therapy.

“Combination therapy with durvalumab and tremelimumab demonstrated antitumor activity in patients with NSCLC regardless of PD-L1 status, including in patients with no evidence of tumor cell membrane PD-L1 staining,” lead author, Scott J. Antonia, MD, PhD, chair of the Department of Thoracic Oncology at Moffitt Cancer Center, said in a statement, according to a Feb. 12 article in OncLive. “The results suggest that this combination has potential as a treatment option for patients with PD-L1–negative tumors whose needs are not addressed by currently available therapies, including immunotherapies.”

The combination therapy will now move on to a Phase III study.

To find out more about the clinical trial results of advanced malignant mesothelioma treatment with tremelimumab see: Intensified Regimen of Tremelimumab Shows Efficacy, Safety in Clinical Trial.

Pleural mesothelioma, a rare form of cancer affecting the lining of the lungs, is highly aggressive and is resistant to many cancer treatments making it a difficult disease to treat effectively. Recent breakthroughs in the use of immunotherapy drugs, such as Keytruda, have significantly improved survival for some patients. This breakthrough could bring these PD-L1 inhibitors to more patients by eliminating the need for PD-L1 screening.

“The latest findings reinforce our belief that the combination strategy we are pursuing is key to the future success of immuno-oncology treatment,” Ed Bradley, MD, senior vice president of Oncology at MedImmune, a subsidiary of AstraZeneca, said in a statement.

AstraZeneca’s Oncology department is dedicated to “Redefining the treatment paradigm to eliminate cancer as a cause of death,” according to its website. The mesothelioma community continues to keep a close eye on trials from companies focused on eradicating cancer or increasing survival for cancer patients.

To find out more about the clinical trial see ClinicalTrials.gov.

Photo credit: AstraZeneca

Sources:

• The Lancet Oncology
  http://secure.jbs.elsevierhealth.com/action/cookieAbsent
• ClinicalTrials.gov
  https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1
• (Feb. 12 article in) OncLive
  http://www.onclive.com/conference-coverage/aacr-2014/pd-l1-predictive-of-response-to-mk-3475-in-melanoma-and-nsclc