Investigational AKT Inhibitor AZD5363 is Active Against Multiple Tumor Types With AKT1 E17K Mutations

“Treatment with the investigational pan-AKT inhibitor AZD5363 led to tumor regression in patients with a variety of types of solid tumors positive for the AKT1 E17K genetic mutation, according to data from a phase I clinical trial expressly designed to recruit patients with these types of tumors. The data were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.

“ ‘The AKT1 E17K genetic mutation was detected in a range of tumor types almost 10 years ago,’ said David M. Hyman, MD, acting director of developmental therapeutics at Memorial Sloan Kettering Cancer Center in New York. ‘Because the mutation is found in only a small fraction of cases of each tumor type and clinical trials have traditionally enrolled patients with only one type of cancer, it was not possible to determine whether the mutation fuels the growth of these tumors and is a viable therapeutic target until the recent advent of basket trials, whereby patients with a range of types of tumor all harboring a defined mutation are enrolled in a single clinical trial.’ “


AACR 2015: New PARP Inhibitor Combination Shows Early Promise for a Wide Range of Cancer Patients

“A combination of two molecularly targeted drugs, olaparib (Lynparza) and the investigational agent AZD5363, was safe and yielded responses in patients with a variety of cancer types, including breast, ovarian, and prostate cancers, regardless of BRCA1/2-mutation status, according to data from the ComPAKT phase I clinical trial presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia (Abstract CT323).

“ ‘In this clinical trial, we evaluated for the first time whether it is possible to safely combine the investigational AKT inhibitor AZD5363 with olaparib, a PARP [poly ADP-ribose polymerase] inhibitor recently approved by the U.S. Food and Drug Administration for treating advanced ovarian cancer associated with defective BRCA genes,’ said Timothy Yap, MD, PhD, National Institute for Health Research Biomedical Research Centre Clinician-Scientist and Consultant Medical Oncologist at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

“ ‘Here, we are reporting results from the dose-escalation portion of the trial, which showed that it was indeed possible to combine these drugs safely,’ continued Dr. Yap. ‘We also observed that several different cancer types responded to the combination, including cancers without BRCA1/2 mutations. These early results are very exciting because preclinical data had suggested that the olaparib and AZD5363 combination had the potential to be effective in a much wider population of patients than just those harboring germline BRCA1/2 mutations.’ “


AKT inhibitor AZD5363 well tolerated, yielded partial response in patients with advanced solid tumors

The investigational drug AZD5363, which has shown activity in preclinical studies, was well tolerated in humans, and two patients with advanced solid tumors showed partial response, according to data presented at the AACR Annual Meeting 2013, held…