Home  >  News
6Sugar_Free_Sweetener.gif
you can get e-magazine links on WhatsApp. Click here
Clinical Trials + Font Resize -

Nuvalent to present new preclinical data supporting potential best-in-class profile for ALK-selective inhibitor NVL-655 at WCLC meeting

Cambridge, Massachusetts
Saturday, August 6, 2022, 14:00 Hrs  [IST]

Nuvalent, Inc., a clinical-stage biopharmaceutical company, announced new preclinical data supporting the potential best-in-class profile of NVL-655 – an ALK-selective inhibitor, and a "Trial in Progress" poster for the phase 1/2 ARROS-1 study of NVL-520 – a ROS1-selective inhibitor. NVL-520 and NVL-655 are central nervous system (CNS)-penetrant kinase inhibitors designed to specifically solve for the dual challenges of kinase resistance and selectivity commonly observed with currently available inhibitors.

The two posters will be presented at the IASLC 2022 World Conference on Lung Cancer (WCLC) Annual Meeting taking place August 6-9, 2022 in Vienna, Austria. The posters will also be available on the Nuvalent website.

"Our presentations at WCLC showcase the value that our collaborations with leading physician-scientists and translational investigators bring towards characterizing and developing our parallel lead programs for patients with non-small cell lung cancer (NSCLC)," said James Porter, Ph.D., chief executive officer of Nuvalent. "We are grateful for our continued collaborations focused on advancing the understanding of resistance to kinase inhibitors, as well as the dedication and support of the phase 1 clinical investigators participating in our ongoing studies for patients with advanced NSCLC and other solid tumours."

"We selected NVL-520 and NVL-655 based on the demonstrated strength of their preclinical profiles and their potential to drive deep, durable responses for patients with ROS1-positive and ALK-positive cancers, respectively. With both programs now under clinical investigation, we remain committed to continued, rigorous preclinical characterization to both deepen our understanding of our programs as well as to support the advancement of tools and models that may help accelerate the development of new therapies for genomically-driven cancers," said Henry Pelish, Ph.D., vice president of biology at Nuvalent. "We are pleased to share data further characterizing NVL-655 in a new patient-derived model of lorlatinib-resistant ALK-positive NSCLC with the treatment-emergent G1202R/T1151M compound resistance mutation, developed by our clinical and translational collaborators at Gustave Roussy."

The MR448re patient-derived model was established from cancer cells retrieved from a NSCLC patient previously treated with four prior ALK kinase inhibitors and most recently progressing following treatment with lorlatinib. Presence of an EML4-ALK fusion and the G1202R/T1151M compound mutation was confirmed by sequencing.

"The rapid development of the MR448re patient-derived model and subsequent evaluation of NVL-655 is a testament to the efficient cooperation between our clinical and translational investigators, and our collaborators at Nuvalent," said Luc Friboulet, Ph.D., investigator at Gustave Roussy. "NVL-655 showed strong antitumor activity in this heavily refractory model, while lorlatinib showed limited inhibitory activity consistent with treatment history. This further supports the differentiating and potentially best-in-class preclinical profile of NVL-655, which has previously demonstrated the ability to retain activity in the presence of a broad spectrum of single and compound ALK resistance mutations while maintaining a wide selectivity window over TRKB."

A "Trial in Progress" poster summarizing the preclinical profile of NVL-520 and clinical trial design of the Phase 1/2 ARROS-1 study (NCT05118789) for NVL-520 will also be presented. This multicenter, open-label, dose-escalation and expansion trial is designed to evaluate NVL-520 as an oral monotherapy for patients with advanced ROS1-positive NSCLC and other solid tumours. The ongoing Phase 1 dose-escalation portion of the study is currently enrolling ROS1-positive NSCLC patients who have previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumours previously treated with any prior therapy. Nuvalent plans to share preliminary dose-escalation data from ARROS-1 in the second half of 2022.

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumours that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumours with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumours that have developed resistance to currently available ROS1 inhibitors, including tumours with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.

Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets.

 

*POST YOUR COMMENT
Comments
* Name :     
* Email :    
  Website :  
   
     
 
truking"
 
 
Copyright © 2016 Saffron Media Pvt. Ltd |