LOXO-292 in Patients With RET-Fusion Lung Cancer

Transcript: Jacob Sands, MD: The data presented on these 2 drugs have been really impressive, particularly relative to the historical studies. The most recent 1 presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer, by Dr Alexander Drilon, looked at selpercatinib and reported out the data in all patients, so patients who had not gotten any prior treatments, treatment-naïve patients, as well as just a broader group of patients. The overall group had a response rate of 68%, and in the treatment-naïve patients, it was 85%. The median progression-free survival overall was about 18 months and not yet reached in the treatment-naïve group.

The efficacy that we’re seeing is this really does match with some of the more effective targeted therapies we’ve seen before, probably somewhere between the EGFR and ALK outcomes. We have yet to see the frontline data on this, although the RET target in itself really correlates well with what we’re seeing within ALK outcomes. There’s still a lot to mature from that data, and so the story will continue, but it is extremely encouraging.

To add to that, the adverse-effect profile, as I’ve mentioned, was very well tolerated, and we continue that. Another important aspect of this is CNS [central nervous system] control, and we saw 91% response rate within the CNS. And an encouraging thing actually is that none of the patients had progression at this point on the targeted therapy. So there was a 91% response rate in the CNS without any progression.

We really see this hitting all the points. We see a good number of responses, we see durability of responses, we see CNS control, and extremely good toxicity profiles. This is all very encouraging. I’ll speak to BLU-667.

Benjamin Besse, MD, PhD: Cabozantinib PFS [progression-free survival] is outstanding compared with what we have seen with platinum-based chemotherapy, or multikinase inhibitors in the same population. The impact is the same that in other molecular selected non—small cell lung cancer patients, such as ROS1 or ALK rearranged in NLCLC [non—small cell lung cancer]. We know that the potency of this drug is much higher than platinum-based chemotherapy, and it should be enough to have the drug registered, because we will never get a PFS of 18 months with a platinum-based chemotherapy.

Toady if you want to treat a RET-positive and ALK patient, you will use either platinum-based chemotherapy or multikinase inhibitor. But the PFS you will expect is around 7 months. With selpercatinib, the PFS expected is 18 months. So it is much better than a treatment we can use today.

Jacob Sands, MD: When we’re seeing all those improvements with durability, better responses, and better toxicity profiles, on all accounts, this really is a significant improvement over the multikinase inhibitors. By having a more directed targeted therapy that’s highly selective, we minimize the toxicity profile, and then on top of this we’re seeing better response rates. At this point, I don’t know that there’s even a discussion to have about multikinase inhibitors versus 1 of these highly selective drugs. It’s kind of like considering a drag race: if you’re going to ride a horse or drive a Ferrari, the difference is really substantial between the 2.

Alexander Drilon, MD: The activity and the safety that we’re seeing with selective RET inhibition is really a substantial improvement compared with older multikinase agents. The rates of toxicity are much higher with these older drugs, and the activity level is lower. As an example, the objective response rate with cabozantinib was approximately 30%. So we’re seeing more than a doubling of response rate with the selective RET inhibitor, and also a much more favorable safety profile. For cabozantinib the dose modification rate was about 75%, meaning 3 of 4 patients needed to have some tweaking of the drug to get down a dose that was tolerable.

Transcript Edited for Clarity