The Road Less Traveled

What routes do new faculty take as they wend their way through post-doctoral training to prepare for where life leads them? In particular, what routes do new faculty members in the Department of Medicine follow? What causes them to choose the fork in the road that takes them to the Stanford campus?

We are asking this question from time to time, and we expect to uncover a globe-full of roads to Stanford. This conversation is with Shivaani Kummar, MD (professor, oncology), who joined the Stanford faculty in January 2015.

Each faculty member comes with a unique background, which often propels him or her into medicine and a particular subspecialty. In Kummar’s case, the focus on a career in medicine began early.

I decided to be a physician at the age of 11

“I decided to be a physician at the age of 11,” she says, “so it wasn’t like I fell into medicine. I did my medical training back in India, and then moved to the US, pursuing a residency in internal medicine at Emory University. Oncology was my first rotation in the US, and I got hooked on it from then on. My fellowship in both hematology and oncology was at the National Cancer Institute (NCI) at the National Institutes of Health. Apart from my clinical rotations, I worked in an immunology laboratory studying graft vs. tumor responses.”

Her first job was as an assistant professor at the Yale Cancer Center, where she got interested in novel therapeutics for cancer. She was recruited back to the NCI to build the Developmental Therapeutics Clinical Program.  For the past few years she was the head of early clinical trials development at the NCI before coming to Stanford.

While at the NCI, Kummar became the principal investigator of M-PACT, a randomized trial of patients with solid tumors resistant to standard therapy; the trial is designed to determine the usefulness of genetic sequencing to improve patients’ outcomes, using mutations found on sequencing to guide the choice of therapy.

Kummar 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 to help expedite drug development timelines.

At Stanford, Kummar is building an integrated translational research program in Phase I drug development. This will be, as she describes it, “a full-fledged Phase I program to span different tumor types with different pathways. Recently, Phase I trials have become more scientifically driven, where they are not only focused on safety but also on informing proof of mechanism and proof of concept.  The idea is to address as many initial questions as possible up front so they can guide what happens to the agent in subsequent Phase II and Phase III trials. Rationally guiding the development of novel anticancer agents will eventually increase the success rate of promising agents, while de-prioritizing agents that don’t achieve the required efficacy.”

Q: What are the advantages to taking part in this integrated Phase I program as opposed to each bench researcher studying a new agent in isolation?

“There are several,” Kummar says. “First is having access to the expertise that it takes to bring an agent from preclinical to clinical; second is the expertise in designing a trial to answer whatever question the person is trying to answer; and third, once a trial is open in the clinical realm, is the monitoring, safety reporting, meeting FDA criteria for reporting, making sure the patient’s safety comes first, and getting all the scientific endpoints answered. The infrastructure in the Phase I Clinical Program will be available to do all those things.”

Q: How will a bench researcher make the transition from the lab to Phase I?

“There are two different ways to interact with the new Phase I program. The first helps out a scientist who has a molecule that he or she has brought all the way forward and is trying to figure out the best path to get it into the patient. The second is if researchers are interested in particular pathways and survival mechanisms; based on the trials that we have open we could provide samples to them to study those pathways and mechanisms further.  In collaboration with the scientists, we could also approach industry partners to study specific agents in defined patient populations to further the understanding of the biology and treatment efficacy. ”

Q: Does the geographic location of Stanford (in addition to the welcome contrast between winter in Bethesda and winter in Palo Alto) play a role in bringing forward molecules that perform well in Phase I trials?

Indeed it does, says Kummar: “Stanford is a very open place with a lot of interaction with biotech and industry. Scientists here are thinking about how to translate what they are doing in the laboratory.  Other places have very good science; it’s just that they don’t think of translating it – the application part of medicine. Here it seems to be a culture where people are trying to define something, find an application for it, and interface with companies here in the Bay Area and beyond.  This is what we’re trying to do in Phase I – find something new and bring it very quickly and safely into patients so that we can develop novel effective therapies for cancers.”