ALKOVE-1 Study Results Summary: NVL-655’s Promising Role in Treating Advanced ALK+ Lung Cancer
The clinical results from the Phase 1 portion of the ALKOVE-1 study is bringing new hope to patients with ALK-positive lung cancer, especially those who have exhausted other treatment options. NVL-655, a fourth-generation ALK inhibitor, has shown unique effectiveness in overcoming resistance to previous treatments, including those with brain metastases and specific resistance mutations.
In the first phase of the ALKOVE-1 trial, researchers tested NVL-655 on 103 patients to determine an effective and tolerable dose. The 150 mg daily dose was identified, and an additional 52 patients have since been treated at this dose. About 60% of participants had brain metastases—some of which were untreated—prior to enrollment, underlining the drug’s potential to manage complex cases.
The trial included patients with a high degree of prior treatment; most had undergone an average of three therapies, and 85% had received Lorlatinib, a third-generation ALK inhibitor. Even in this heavily pretreated population, NVL-655 demonstrated meaningful results: about 40% of patients experienced measurable tumor shrinkage. In those with certain ALK resistance mutations, this response rate increased to 80%, with a median response duration of approximately 14 months.
Importantly, NVL-655 is designed to minimize side effects that often accompany other treatments, especially neurological ones. Unlike other ALK inhibitors, NVL-655 has limited inhibition of the TRK protein, reducing the risk of neurological side effects. In this study, side effects were minimal, with only 15% of patients requiring dose reductions and just 2% discontinuing treatment due to adverse effects.
These positive results have earned NVL-655 a breakthrough therapy designation from the FDA, allowing for faster development and, potentially, earlier approval. The trial continues to enroll patients in the Phase 2 portion of the trial, adding to the growing body of evidence supporting NVL-655’s potential.
If approved, NVL-655 would join an expanding arsenal of treatments for ALK-positive lung cancer, adding to second- and third-generation TKIs, localized treatments, chemotherapy, and innovative combinations in ongoing clinical trials. These therapeutic advances are transforming the landscape for ALK+ lung cancer, signaling that Stage 4 ALK-positive lung cancer could soon be managed as a chronic illness rather than a life-threatening one. The rapid evolution of ALK-positive lung cancer treatment is offering patients and their families more hope than ever before.
A heartfelt thank you to the ALK-positive lung cancer patients and dedicated researchers who have contributed to this trial. Your courage and commitment are driving progress and inspiring a brighter future in ALK-positive lung cancer treatment.
For further information about the NVL-655 trial, see Jeff Sturm’s excellent article in this newsletter.
Clinical Trials Currently Recruiting for ALK-positive Cancers.*
General Information About Clinical Trials
Patient-led Research: ALK Life Study
ALK Positive needs your participation to help develop companies and oncologists develop new treatments, practices and policies for ALK-positive lung cancer patients. The ALK Life Study is a global registry for ALK-positive NSCLC patients that was established to explore their diagnostic and treatment journeys. The survey covers the first symptoms presented at the clinic, diagnostic tests, referral to lung cancer specialists, time of diagnosis, and treatment initiation through to today. To register and complete the survey, please click here: Longitudinal Survey of ALK+ Cancer Patients: Self Registration
As of October 2024, there are at least 50 clinical trials that are recruiting specifically for people with ALK-positive lung cancer. Many of these trials have multiple sites worldwide. It is difficult for every oncologist to be aware of all the trials available. You can advocate for yourself and find a clinical trial that may be a good fit for you at any juncture in treatment.
*The ALK Positive Clinical Trials Spreadsheet was developed by the ALK Positive Medical Committee. The database is updated monthly. Disclaimer: these trials have been consolidated by volunteers and should not be considered exhaustive. Listing of these trials is not an endorsement, and ALK Positive does not recommend one trial over another. Please talk with your doctor about these or any trials you are interested in.
By Ellee Urban with assistance from ChatGPT.