Professor - Med Center Line, Medicine - Oncology
Professor - Med Center Line, Radiology - Rad/Molecular Imaging Program at Stanford
Member, Stanford Cancer Institute
Director, Phase I Clinical Research Program, Division of Oncology, Stanford School of Medicine (2015 - Present)
Professor of Medicine, Department of Medicine (2015 - Present)
Current Research and Scholarly Interests
Dr. Kummar’s research interests focus on developing novel therapies for cancer. She specializes in conducting pharmacokinetic and pharmacodynamic driven first-in-human trials tailored to make early, informed decisions regarding the suitability of novel molecular agents for further clinical investigation. Her studies integrate genomics and laboratory correlates into early phase trials. She is interested in alternate trial designs to facilitate rational drug selection based on human data and help expedite drug development timelines. She has published numerous articles in medical journals and serves on a number of national and international scientific committees.
The root causes of pharmacodynamic assay failure
SEMINARS IN ONCOLOGY
2016; 43 (4): 484-491
Robust pharmacodynamic assay results are valuable for informing go/no-go decisions about continued development of new anti-cancer agents and for identifying combinations of targeted agents, but often pharmacodynamic results are too incomplete or variable to fulfill this role. Our experience suggests that variable reagent and specimen quality are two major contributors to this problem. Minimizing all potential sources of variability in procedures for specimen collection, processing, and assay measurements is essential for meaningful comparison of pharmacodynamic biomarkers across sample time points. This is especially true in the evaluation of pre- and post-dose tumor biopsies, which suffer from high levels of tumor insufficiency due to variations in biopsy collection techniques and significant specimen heterogeneity within and across patients. Developing methods to assess heterogeneous biopsies is necessary in order to evaluate a majority of tumor biopsies collected for pharmacodynamic biomarker studies. Improved collection devices and standardization of methods are being sought in order to improve the tumor content and quality of tumor biopsies. In terms of reagent variability, we have found that stringent initial reagent qualification and quality control of R&D-grade reagents is critical to minimize lot-to-lot variability and prevent assay failures, especially for clinical pharmacodynamic questions, which often demand assay performance that meets or exceeds clinical diagnostic assay standards. Rigorous reagent specifications and use of appropriate assay quality control methodologies help to ensure consistency between assay runs, laboratories and trials to provide much needed pharmacodynamic insights into the activity of investigational agents.
View details for DOI 10.1053/j.seminoncol.2016.06.006
View details for Web of Science ID 000384870100007
View details for PubMedID 27663480
Establishing proof of mechanism: Assessing target modulation in early-phase clinical trials
SEMINARS IN ONCOLOGY
2016; 43 (4): 446-452
Since modulation of the putative target and the observed anti-tumor effects form the basis for the clinical development of a molecularly targeted therapy, early-phase clinical trials should be designed to demonstrate proof-of-mechanism in tissues of interest. In addition to establishing safety and the maximum tolerated dose, first-in-human clinical trials should be designed to demonstrate target modulation, define the proposed mechanism of action, and evaluate pharmacokinetic-pharmacodynamic relationships of a new anti-cancer agent. Assessing target modulation in paired tumor biopsies in patients with solid tumors presents multiple challenges, including procedural issues such as patient safety, ethical considerations, and logistics of sample handling and processing. In addition, the availability of qualified biomarker assay technologies, resources to conduct such studies, and real-time analysis of samples to detect inter-species differences that may affect the determination of optimal sampling time points must be taken into account. This article provides a discussion of the challenges that confront the practical application of pharmacodynamic studies in early-phase clinical trials of anti-cancer agents.
View details for DOI 10.1053/j.seminoncol.2016.06.002
View details for Web of Science ID 000384870100003
View details for PubMedID 27663476
- Developing therapies for rare tumors: opportunities, challenges and progress EXPERT OPINION ON ORPHAN DRUGS 2016; 4 (1): 93-103
Delivering on the promise: poly ADP ribose polymerase inhibition as targeted anticancer therapy.
Current opinion in oncology
2015; 27 (6): 475-481
The article presents the rationale, clinical development, and current status of poly (ADP ribose) polymerase inhibitors (PARPis) as anticancer agents.The recent approval of olaparib in heavily pretreated patients with advanced ovarian cancer carrying a BRCA1/2 mutation represents a significant therapeutic advance for patients with this difficult to treat disease. Though olaparib is the first agent in this class to be approved, multiple PARPis are in various stages of clinical development, including in combination with other treatment modalities such as radiation, antiangiogenic agents, and cytotoxic chemotherapies.Clinical benefit has been observed with PARPis in patients with advanced BRCA1/2 mutant ovarian and breast cancers. Various PARPis, either as single agents or in combination, are being evaluated in the neoadjuvant, adjuvant, and metastatic settings.
View details for DOI 10.1097/CCO.0000000000000238
View details for PubMedID 26447876
- Delivering on the promise: poly ADP ribose polymerase inhibition as targeted anticancer therapy CURRENT OPINION IN ONCOLOGY 2015; 27 (6): 475-481