Phase 2 Trial Assessing Novel TKI Begins in ALK-Positive NSCLC, Solid Tumors

A novel TKI is being evaluated in a phase 2 trial for patients with ALK-positive NSCLC.

The phase 2 portion of the ALKOVE-1 trial has started and aims to assess the novel ALK-selective tyrosine kinase inhibitor, NVL-655, for the treatment of ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

NVL-655 is designed to penetrate the central nervous system to potentially improve treatment for patients with brain metastases (the spread of cancer cells from their original location to another part of the body), according to a press release from Nuvalent, the treatment’s manufacturer. This treatment is also meant to remain active in tumors that become resistant to first-, second- and third-generation ALK inhibitors.

“The transition of our NVL-655 program into phase 2 advances a second, parallel opportunity towards our goal of bringing potential best-in-class therapies to patients as efficiently as possible,” Darlene Noci, chief development officer at Nuvalent, said in the release. “This sense of urgency is reflected in the thoughtful design of the phase 2 portion of the ALKOVE-1 trial, which aims to accelerate the clinical investigation that may support a potential marketing application towards an initial approval for previously treated patients with ALK-positive NSCLC.”

In this part of the trial, researchers aim to assess the objective response rate (the percentage of patients with a complete or partial response to treatment within a period of time) of NVL-655 at the recommended dose of 150 milligrams once per day, according to the trial’s listing on ClinicalTrials.gov. Other areas of interest include time to response, duration of response, overall survival (the time from the start of treatment when a patient with cancer is still alive), progression-free survival (the time during and after treatment when a patient with cancer lives without disease worsening) and clinical benefit rate (patients who achieve a partial remission, complete remission or have stable disease for at least six months).

“We believe there is the potential for NVL-655 to provide durable responses while minimizing [side effects] and dose-limiting toxicities for patients with ALK-positive cancers throughout the treatment paradigm,” Noci said.

Patients enrolled in this phase 2 study are 18 years and older and have locally advanced or metastatic NSCLC with an ALK arrangement. Patients must also have adequate bone marrow reserve and organ function, according to the ClinicalTrials.gov listing.

Researchers are currently recruiting patients and are aiming to enroll an estimated 320 patients with ALK-positive NSCLC or other solid tumors. The ALKOVE-1 trial is estimated to be completed in March 2026, according to the listing.

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