Nuvalent chases after Nuvation in ROS1 lung cancer

 Nuvalent has said it is on course to file for approval of its ROS1 inhibitor zidesamtinib as a lung cancer treatment, although rival Nuvation Bio has beaten it to market.

Cambridge, Massachusetts-based Nuvalent has reported the results of its phase 1/2 ARROS-1 trial of zidesamtinib in previously treated patients with ROS1-mutated non-small cell lung cancer (NSCLC), saying the study is "aligned" with the FDA's position on regulatory submissions for this type of cancer.

It now plans to submit the drug via a rolling submission next month, with the aim of completing the filing in the third quarter, as it chases after Nuvation and its recently FDA-approved rival Ibtrozi (taletrectinib).

Like Ibtrozi, zidesamtinib has been held up as a next-generation ROS1 inhibitor that could improve on other drugs in the class, like Pfizer's first-to-market Xalkori (crizotinib), Roche's Rozlytrek (entrectinib), and Bristol Myers Squibb's Augtyro (repotrectinib).

Ibtrozi has approval as a first-line alternative to the established drugs, however, while the ARROS-1 data will only allow Nuvalent to seek approval in patients previously treated with ROS1 drugs, at least initially, although, the company has also reported encouraging preliminary data this morning in a treatment-naïve population.

In the study, there was a 44% objective response rate (ORR) among 117 pre-treated patients – around half of whom had received at least two earlier therapies – after treatment with zidesamtinib. In 78% of responders, the cancer was still being held at bay after 12 months, falling to 62% at 18 months.

The ORR rose to 51% in a subgroup of patients who had received prior treatment with just one ROS1 therapy, with an estimated durability of response of 93% at both the 12- and 18-month landmarks.

Nuvalent has also reported the first data from another study in ROS1 inhibitor-untreated patients, who may have had prior chemotherapy, revealing an ORR of 89% in 35 subjects that is in the same ballpark as was seen with Ibtrozi in the TRUST-1 and TRUST-2 trials that underpinned its approval.

The company said it "continues to engage with the FDA on potential opportunities for line-agnostic expansion."

It is estimated that approximately 2% of the million or so people around the world who are diagnosed with NSCLC each year have ROS1-positive disease, which has a tendency to progress quickly and spread to other parts of the body, particularly the brain.

Meanwhile, Nuvalent has also given an update on its ALK inhibitor neladalkib, saying that the startup of its ALKAZAR trial comparing the drug to Alecensa (alectinib) as a front-line treatment for ALK-positive NSCLC is gathering pace and enrolment is due to start in the latter half of 2025.

https://pharmaphorum.com/news/nuvalent-chases-after-nuvation-ros1-lung-cancer