Phase 2 Trial to Investigate Novel Drug in ROS1-Positive Lung Cancer

A phase 2 trial will investigate a new drug for patients with ROS1-positive cancer.

The phase 2 portion of the ARROS-1 clinical trial recently launched, investigating the novel drug, NVL-520, for patients with pretreated ROS1-positive non-small cell lung cancer (NSCLC) or other solid tumors, according to an announcement from Nuvalent, the manufacturer of the drug.

Based on findings from the earlier phase 1 trial, the Food and Drug Administration (FDA) recommends that phase 2 uses a 100 mg daily dose of NVL-520, as that dose maintained steady state plasma levels above the target thresholds, had a favorable tolerability profile and showed no clinically significant drug-related safety issues.

"The ARROS-1 trial was designed to support a seamless transition from first-in-human dose-exploration in a heavily pre-treated population to a phase 2 portion designed with the potential to support registration. We are thrilled to achieve this milestone towards our goal of bringing a potential best-in-class therapy to patients with ROS1-positive NSCLC as efficiently as possible," said Darlene Noci, chief development officer at Nuvalent, in a press release.

NVL-520 is a ROS1-selective tyrosine kinase inhibitor (TKI), which are drugs that work by blocking certain signals that tell cancer cells to grow and divide, according to the National Institutes of Health. Notably, NVL-520 can get into the brain. Per the press release, penetrating the brain is an attractive treatment mechanism because it fills a need for patients whose disease became resistant to therapy; can decrease side effects related to the central nervous system associated with TRK inhibitors; and may be an option for patients with brain metastases who are not eligible for other ROS1-directed TKIs.

Researchers in the ARROS-1 trial plan on enrolling approximately 225 patients with ROS1-positive NSCLC or other solid tumors that has not previously been treated with a TKI. Participants — who are being recruited in North America, Europe, Asia and Australia — will fall into one of five groups:

• Those with advanced/metastatic ROS1-positive NSCLC that have been treated with one line of chemotherapy and/or immunotherapy
• Those with advanced/metastatic ROS1-positive NSCLC that have been previously treated with wither Xalkori (crizotinib) or Rozyltrek (entrectinib) with no prior chemotherapy or immunotherapy
• Those with advanced/metastatic ROS1-positive NSCLC that have been previously treated with wither Xalkori (crizotinib) or Rozyltrek (entrectinib) and one prior line of platinum-based chemotherapy, with or without immunotherapy
• Patients with advanced or metastatic ROS1-positive NSCLC treated two or more prior ROS1 TKIs (Xalkori or Rozyltrek) and up to one line of chemotherapy and/or immunotherapy
• The exploratory cohort of patients with any advanced or metastatic ROS1-positive solid tumors — including those with NSCLC who are not otherwise eligible for the other groups — and who progressed on prior treatment

"Support for the Phase 2 cohort design includes the demonstrated nonclinical activity of NVL-520 in the periphery and in the CNS, and its selective inhibition of ROS1 and ROS1 drug-resistance mutant G2032R over the structurally-related TRK kinases. Combined with the broad clinical activity and favorable tolerability observed to date in heavily pre-treated patients in the Phase 1 portion of ARROS-1, we believe there is the potential for NVL-520 to provide durable responses while minimizing adverse events and dose limiting toxicities for patients with ROS1-positive cancers throughout the treatment paradigm,” Noci explained.

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