Oncology R&D Will Follow Divergent Paths, Experts Say at JPM Event

What’s the best way to follow the money in oncology research and development? There won’t be a single path to success in the near future, according to experts on an Endpoints News panel gathered January 14, 2025, during the JPMorgan conference in San Francisco, California.

A decade after the immunotherapy revolution, combination therapies abound and newer technologies such as antibody-drug conjugates, T-cell engagers, and radiopharmaceuticals are gaining ground. A key challenge, noted moderator John Carroll, Endpoints’ founder and editor, is the wide gulf between the cutting-edge technology in leading academic centers and what patients may encounter in smaller community hospitals. Carroll has written about his own experience working to hunt down the best doctors and treatments after a diagnosis of Merkel cell carcinoma.

Joining Carroll were:

• Marjorie Green, MD, senior vice president, head of Oncology Clinical Development, Merck.
• Maha Katabi, PhD, CFA, general partner, Sofinnova Investments.
• Stephen Hahn, MD, CEO of Harbinger Health and the former FDA commissioner.
• Dan Malarek, PhD, CEO of Foundation Medicine, which sponsored the panel.

Marjorie Green, MD | Image credit: LinkedIn

Green highlighted the shift from a “universal focus on immunology” toward a “more diversified approach to oncology,” one that takes into account both approaches that have worked as well as known mechanisms of resistance. Merck’s development portfolio features more than 25 assets involving multiple cancer drivers, which offers choices for both combinations and sequencing.

Carroll noted the “tensions” in where to put investment dollars. “There's been obviously a movement towards drugs that have a big impact with a large patient population; at the same time, in terms of gaining some of the most dramatic effects, you go to a very small populations, and sometimes the individual patient,” he said. How do companies select a path?

Maha Katabi, PhD, CFA | Image credit: LinkedIn

Some targeted oncology indications have not delivered on their promise, Katabi said, and thus lost investment dollars. The 2025 meeting, by contrast, saw transactions around well-known targeted agents. “The interest remains,” she said, “but I think the shift that I've seen is targeted oncology that addresses a much broader patient segment than the specific genetic mutations.”

Effects of the IRA

Carroll turned to the Inflation Reduction Act (IRA), noting that companies now have a different timeline surrounding development of cancer drugs. As experts explained during a spring forum at Rutgers Business School, sponsors may not be able to get that first indication before learning as much as they can about the drug, and then go to regulators for multiple indications at once. Carroll asked Hahn for insights on how companies are responding to this new landscape.

“There is now is a different discussion around indications,” Hahn said. As an example, he said a company that was focused on endometrial cancer may look at the size of that market and consider the complications of the IRA, and say, “We’ve got to go into breast cancer.”

Stephen Hahn, MD | Image credit: MD Anderson

Hahn doesn’t think the traditional approach of establishing a presence in one indication before moving on to others has ended; however, the IRA is definitely having an impact. He agreed with Carroll that “we really do need to move to away from our classical definitions of the indications and more toward the target as it spreads across a number of different cancers.”

Of note, Hahn added, “This is highly dependent upon diagnostics. And if you think about where we believe HHS and FDA is heading, from a preemptive medicine point of view, the point of cancer being one of them, moving drugs to an earlier stage, it's highly dependent upon the diagnostic space. The diagnostic space is a little bit of a mess right now.” With more than 85% of the cancer drugs FDA approved in 2024 having a companion diagnostic, this approach “is here to stay.”

What’s Coming in Diagnostics

Carroll said for all the talk about new technologies in cancer treatment, “When you're actually engaged in cancer treatment, you constantly run into these really old technologies.” In his own cancer treatment, Carroll said he’s had tests that are 50 years old.

Dan Malarek, PhD | Image credit: Foundation Medicine

On the other end of the spectrum, Malarek said Foundation Medicine is developing the Foundation One Monitoring Assay, which will streamline patient monitoring by telling patients and physicians not only whether a therapy is working but also why it’s not working if that’s the case.

“What are those resistance mutations?” Malarek asked. By reporting this upfront, the physician can make a decision in the moment on what to do next. With this tool, he said, the next step is to create partnerships with share information with biopharma.

In addition, Katabi said, technologies that were new a few years ago are now advancing into wider use. More practices and cancer centers have the ability to use circulating tumor DNA testing and liquid biopsies to identify whether patients have responded to therapy—and whether it should continue. “So, that opens up a whole avenue of interactions with regulators, but also with payers,” she said.

Bringing the Best to Everyone

For Carroll, these advances still come back to the question of how to bring these advances to everyone—especially the patient in the community hospital—where he received his cancer diagnosis and initial advice for chemotherapy that he realized was the wrong answer.

“Cancer treatment is often defined by the major institutions, like MD Anderson and Dana Farber and so on, but it's really practiced in the community,” Carroll said. “And you know, my first experience at the community level was pretty abysmal…. The first diagnosis I got came back with a recommendation for chemo, which would have killed me after about 2 or 3 months of chemo—and then, you flatten the immune system. That's the last thing you want to do with Merkel cell carcinoma.

“I look at this division between the 90% of community-based cancer treatment and the rest,” he said. “How do you get the newer technologies into the community?”

The panelists had a variety of answers. Green said community oncologists do their best to keep up with guidelines updates from the National Comprehensive Cancer Network, which end up on clinical pathways. The challenge in the community is, “You see every cancer. And so keeping up with the volume of data is tricky.”

Malarek agreed. He said genomic testing rates at the community level have increased, but they remain around 30% to 40%, when they should be at 90%. Hahn said that phase 3 trials should be smaller and less complicated to get novel therapies into the market more quickly, and several speakers called for greater use of real-world data.

Driving Change at FDA

FDA is in need of reform, the panelists agreed, even disruption. China is no longer limited to small iterations or “me too” drugs, and the atmosphere must shift. Johns Hopkins’ Marty Makary, MD, MPH, FACS, a hepatobiliary and pancreatic surgeon, is nominated to be the new FDA commissioner, and is seen as a bridge between the “disruptor” elements of the second Trump team and the more conventional FDA leaders of the past. Hahn thinks there will be resistance to change within the agency, but he’s hopeful, too, that the new administration will bring more transparency.

“Like any big institution, and particularly a big government institution, there are cultural barriers to significant change, and we're going to see that,” he said. “I seriously believe that there will be a big attempt at disruptive change, and my sincerest hope is that is in a positive direction.”

“This administration had been all about pushing innovation forward, and you have to do it the right way,” Hahn continued. “[It] remains to be seen whether it can be done, but I think there'll be a critical look at leadership in the agency. I think there'll be a critical look at the review process. Can we standardize it? Can we make it more transparent? And what can we do to enable actually information to come to the fore?”