Clinical Trials: What’s New in Oncology?

Novel Immunotherapy Shows Promise for Various Types of Cancers

Since the approval of Provenge and Yervoy immunotherapies, development of anti-cancer immune therapies has gained a lot of momentum. Bristol-Myers Squibb’s and Ono Pharma’s antibodies targeted toward PD-1 and PD-L1 molecules are showing great promise for the treatment of non-small cell lung cancer, melanoma, kidney cancer and ovarian cancer. PD-1 is a molecule found on T-cells, when PD-1′s ligand PD-L1 binds to it T-cells loose activity or die. These targeted antibodies block the binding of ligand to receptor and in doing so maintain anti-tumor T-cell activity.   

Investigational Drug Trastuzamab Emtansine Delays Progression of Advanced HER2-positive Breast Cancer

Trastuzamab emtansine  (T-DM1) is a combination drug containing the trastzamag (Herceptin) antibody attached to chemotherapeutic agent DM1. DM1 is toxic when delivered alone into the bloodstream, combining it with an antibody which has specificity for a given antigen limits its potential wide range toxicity to only cells positive for Her2. Women treated with T-DM1 benefited from a 3 month progression free survival compared to patients treated with lapatinib (Her2/neu and EGFR inhibitor) and chemotherapeutic, capecitabine (DNA synthesis inhibitor) combination treatment.

The FDA is expected to decide on the approval of T-DM1 on Feb. 26, 2013.

Improved Therapy for Rare Form of Brain Cancer
Brain tumor resized 600
Clinical trials conducted on patients with anaplastic oligodendrogliomas, a rare form of brain cancer (anaplastic oligodendrogliomas account for less than 10% of brain cancers) were found to live much longer if treated with a combination of chemotherapy and radiation therapy rather than radiation alone. These findings came after a long term (10 yr) follow up in patients whose tumors had mutations or deletions in both chromosomes 1 and 19 which account for about half of all cases.  Patients who lacked those mutations did not show any benefit to the combination treatment.  This work highlights the importance of genetic screening of a patients cancer and tailoring of cancer treatments.  

Promising New Treatment for Drug-Resistant Leukemia

Chronic Myeloid Leukemia (CML) patients who have failed all therapeutic options now have a new drug option, ponatinib. This drug is efficacious at inhibiting various mutations of the BCR-ABL fusion protein known to cause CML. First and second-generation BCR-ABL inhibitors imatinib, desatinib and nilotinib are effective in the treatment of CML but eventually acquired resistance develops towards these treatments or in some cases there is no response. Resistance to these therapies is largely attributed to mutations on BCR-ABL. Ponatinib is said to overcome these limitations based on its intelligent design that renders it capable of blocking BRC-ABL’s various mutations.

The FDA approved ponatinib on Dec. 14, 2012 for the treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). 

About Jemima Escamilla

Jemima Escamilla Ph.D in Molecular and Medical Pharmacology at the UCLA David Geffen School of Medicine. Her research focus integrates hormonally regulated cancer progression and cancer immunology.