ASH Clinical News July 2017 V2 - Page 40

Interview Richard Pazdur, MD program, biorepositories, and electronic medical record systems – this informa- tion will play a greater role in developing treatments for hematologic malignan- cies, as well as selecting the appropriate patient population for those agents. The growing evidence about the role genetic mutations (particularly driver muta- tions) play in cancer risk and prognosis has also provided easily identifiable tar- gets for new product development – for instance, the approvals of imatinib, which targets BCR-ABL, and the re- cent approval of midostaurin, which targets FLT3. How do you see drug labels/ indications changing within hematology as more targeted approaches become available? Targeted approaches have certainly progressed and, as precision medi- cine moves forward, the targets of therapy have evolved from a tissue- or organ-based approach to a gene- or pathway-based targeting paradigm. Product indications and labeling will have to evolve accordingly. As the OCE director, I hope to be able to integrate FDA resources to sup- port regulators and researchers in this transition. For instance, approval decisions will increasingly describe the use of complementary and companion diagnostics – tests that identify patients whose cancers harbor the targeted abnormalities – for the safe and effective use of these drugs. Companion diagnostics also will provide information about how a drug might be used or which patients should receive a particular drug. The FDA has typically ap- proved companion diagnostics under a “one drug, one diagnostic” paradigm, but advances in molecular sequencing mean that we are likely to shift to a “one drug, a panel of diagnostic markers” paradigm. How could the development and approval of targeted therapies impact registration trial designs? For decades, the clinical development of cancer treatments has followed the conventional phase I, phase II, and phase III paradigm. One of the OCE’s ongoing initiatives is an effort to modernize eligibility criteria and patient selection for oncology clinical trials. 1 It has become clear to us that, far too often, the eligibility criteria for enrolling patients in cancer clinical trials appear to be simply cut- and-pasted from one trial to another, without a scientific or justifiable 38 ASH Clinical News basis. We need a more thoughtful approach. We encourage clinical trial designs that allow for enrollment of patients who reflect the real-world popula- tion likely to receive the therapy under investigation, including patients with HIV or a history of prior cancers and older patients who, traditionally, might be excluded from clinical trials. 2 Recently, researchers have discovered early biomarkers of disease prognosis, which has facilitated better patient selection for drugs. These discoveries have prompted a move away from the sequential, three-phase design to a more seamless approach – adding cohorts to a first-in-human trial to investigate doses and activity in a variety of cancers. This type of approach proved suc- cessful with the investigation of the PD-1 inhibitor pembrolizumab, as we described in a perspective article in the New England Journal of Medicine. 3 Pembrolizumab was initially studied in a first-in-human trial to determine the safety and recommended dose of pembrolizumab. When investiga- tors observed early impressive response rates and durations of response, par- ticularly among patients with metastatic melanoma or non-small cell lung cancer, cohorts were added to assess efficacy in these two patient populations, as well as to