In this episode of OncLive On Air, Zev A. Wainberg, MD, sat down with OncLive to discuss the rapidly evolving landscape of KRAS-directed therapy in pancreatic ductal adenocarcinoma (PDAC), from pan-RAS inhibition to KRAS G12D–specific strategies, and what the next several years of clinical investigation may look like for patients with this difficult-to-treat malignancy.<br>Wainberg is a professor of medicine at the David Geffen School of Medicine at UCLA, co-director of the UCLA GI Oncology Program, and medical director of the UCLA Pancreas Cancer Center, where he also serves as director of the Early Phase Clinical Research Program at the Jonsson Comprehensive Cancer Center.<br>This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive

KRAS-Directed Therapy Enters a New Era in Pancreatic Cancer: With Zev A. Wainberg, MD

OncLive® On Air

# Full Transcript

**Podcast:** OncLive® On Air

## Participants

- **Courtney Flaherty** (OncLive)
- **Zev A. Wainberg, MD** (None)
- **Zev A. Wainberg, MD** (None)

## Transcript

Welcome to OncLive On Air. I'm your host today, Courtney Flaherty. OncLive On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In this episode of OncLive On Air, Zev A. Wainberg sat down with OncLive to discuss the rapidly evolving landscape of KRAS-directed therapy and pancreatic ductal adenocarcinoma, from pan-RAS inhibition to KRAS-D12D-specific strategies. He also discussed what the next several years of clinical investigation may look like for patients with this historically difficult-to-treat malignancy.

For decades, KRAS was considered an undruggable target in pancreatic cancer, but now that we have agents like diraxin-RASIB and other mutation-specific inhibitors generating really promising clinical data, how would you characterize the current state of KRAS-directed therapy, and what has enabled these recent advances?

It's really quite different than it's ever been before. If you look back in history, we haven't had quite this moment for a while, so a simple answer is biological chemistry, structural chemistry. All of these things have really led the way. So if you look at the companies and the people that got us to this place, it's all of those chemists and all of those people's pursuits of RAS as this target.

And so once they all figure that out, I think now it becomes an open floodgate in terms of opportunities to develop multiple RAS inhibitors. Diraxin-RASIB is definitely the big name here. So what have we seen with this agent so far as monotherapy in combination in these different settings, and why do you think that it really opens up those floodgates, as you said?

Diraxin-RASIB What's unique about it is that it blocks all RAS. So if you're thinking about a way to test the drug in the largest amount of patients possible, you do it by blocking all RAS. So they were able to develop a very elegant compound that blocks all RAS, wild-type and mutant. And when you have a disease that's so dependent on RAS, like pancreatic cancer, you can test it pretty efficiently and quickly in that cancer.

So that's really what it comes down to, and that's what was done. The results, obviously, of the RAS-LW-302 study are confirmatory that it works better than chemotherapy. But it's just really the first step, right? Now it's going to be about how to use it, when to use it, move it to earlier lines, which we're already doing, of course. Will there be differences in pan-RAS versus other RAS inhibitors? All of that is going to take quite a while to sort out, but that's what we're going to be doing the next number of ...

KRAS-Directed Therapy Enters a New Era in Pancreatic Cancer: With Zev A. Wainberg, MD

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KRAS-Directed Therapy Enters a New Era in Pancreatic Cancer: With Zev A. Wainberg, MD

Transcript

Built for investment professionals

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