Trial reportCancer discovery2024
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.
Trial report in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.Molecular cancer · 2024Trial
- Article
- A new chapter in targeting kinase enzymes in cancer.Nature · 2026Article
- Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Molecules of lung cancer - fusion alterations in nonsmall cell lung cancer: biology and diagnostic considerations.Breathe (Sheffield, England) · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- The novel ALK K1150dup mutation mediates resistance to frontline lorlatinib and retains sensitivity to gilteritinib.NPJ precision oncology · 2026Article
- First Things First: Navigating ALK-Positive Metastatic Non-Small Cell Lung Cancer Treatment Options-A Podcast.Targeted oncology · 2026Article
- Review
- Research progress of small molecule targeted drugs for non-small cell lung cancer.Frontiers in oncology · 2026Review
- Medicinal Chemistry of Fourth-generation Tyrosine Kinase Inhibitors.Mini reviews in medicinal chemistry · 2026Review
- Construction and verification of a prognostic model for prostate cancer based on ribosome biogenesis-related genes.BMC medical genomics · 2025Article
- Advances in Targeted Therapy for Non-Small-Cell Lung Cancer: Current Progress and Future Directions.International journal of molecular sciences · 2025Review
- Preclinical Prediction of Resistance Mutations and Proposal of Sequential Treatment Strategies for ALK-positive Lung Cancer Using Next-generation ALK Inhibitors.Pharmaceutical research · 2025Article
- Clinical Features, Molecular Biology, and the Metastatic Microenvironment in Lung Cancer Brain Metastases: Implications for Treatment Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2025Review
- Lorlatinib in ALK-positive non-small cell lung cancer: final survival data that reshape the therapeutic landscape.Translational lung cancer research · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
Abstract
Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion-positive non-small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested. In vitro, NVL-655 inhibits diverse ALK fusions, activating alterations, and resistance mutations, showing ≥100-fold improved potency against ALKG1202R single and compound mutations over approved ALK TKIs. In vivo, it induces regression across 12 tumor models, including intracranial and patient-derived xenografts. NVL-655 inhibits ALK over TRK with 22-fold to >874-fold selectivity. These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion-positive non-small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations. Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.