A woman on the beach, facing away, walking towards the waves. A woman on the beach, facing away, walking towards the waves.

Pipeline

Created for the Challenge

Nuvalent’s novel drug candidates solve for the dual challenges of kinase resistance and selectivity, with the goal of enabling durable responses for patients with cancer.

Nuvalent Pipeline

Lead Indication
Product
Candidate
Discovery
IND Enabling
Phase 1
Phase 2
Phase 3
ROS1 NSCLC
NVL-520
ALK NSCLC
NVL-655
HER2 NSCLC
NVL-330
ROS1 NSCLC Product candidate: NVL-520
phase 2
ALK NSCLC Product candidate: NVL-655
phase 2
HER2 NSCLC Product candidate: NVL-330
IND ENABLING
Programs

ROS1 fusions are an oncogenic driver alteration found in up to 3% of patients with non-small cell lung cancer (NSCLC). The clinical utility of approved therapies for ROS1-driven NSCLC is limited by emergent resistance mutations as well as central nervous system (CNS) disease.

 

NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim of addressing the combined medical needs of:

  • Treating tumors driven by ROS1 that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R “solvent front” resistance mutation,
  • Avoiding inhibition of the structurally-related tropomyosin receptor kinase (TRK) family, and
  • Treating brain metastases.


ROS1-selectivity is emphasized to minimize CNS adverse events related to off-target inhibition of TRK and potentially drive durable responses for patients with ROS1-mutant variants. In addition, NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases.

The Phase 2 portion of the ARROS-1 Phase 1/2 clinical trial of NVL-520 for patients with advanced ROS1-positive NSCLC and other solid tumors is now enrolling. To learn more, please visit www.clinicaltrials.gov (NCT05118789).

ALK fusions are an oncogenic driver alteration found in up to 5% of patients with non-small cell lung cancer (NSCLC). The clinical utility of approved therapies for ALK-driven NSCLC is limited by emergent resistance mutations as well as central nervous system (CNS) disease.

 

NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim of addressing the combined medical needs of:

  • Treating tumors driven by ALK that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with both single or compound treatment-emergent ALK mutations such as those involving the G1202R “solvent front” mutation,
  • Avoiding inhibition of the structurally-related tropomyosin receptor kinase (TRK) family, and
  • Treating brain metastases.


ALK-selectivity is emphasized to minimize CNS adverse events related to off-target inhibition of TRK and potentially drive more durable responses for patients with ALK-mutant variants. In addition, NVL-655 has been optimized for brain penetrance to improve treatment options for patients with brain metastases.

The Phase 2 portion of the ALKOVE-1 Phase 1/2 clinical trial of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors is now enrolling. To learn more, please visit www.clinicaltrials.gov (NCT05384626).

 

Mutations in human epidermal growth factor receptor 2 (“HER2” or “ERBB2”) occur in up to 4% of metastatic non-small cell lung cancer (NSCLC), with in-frame deletions, insertions, or duplications in exon 20 accounting for 90% of cases (collectively “HER2ex20”). Approximately 20% of patients with HER2 mutant NSCLC present with brain metastases, with the percentage increasing upon treatment. There are limited therapeutic options targeting these mutations.

 

NVL-330

NVL-330 is a novel, brain-penetrant HER2-selective tyrosine kinase inhibitor designed with the aim to address the combined medical needs of:

  • Treating tumors driven by HER2ex20,
  • Avoiding treatment-limiting adverse events due to off-target inhibition of wild-type EGFR, and
  • Treating brain metastases.


HER2-selectivity is emphasized to minimize potentially dose-limiting adverse events associated with inhibition of the structurally related wild-type EGFR kinases such as skin rash and gastrointestinal toxicity. In addition, NVL-330 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases.

 

At Nuvalent we are combining our close partnerships with physician-scientists, rigorous target selection, and disciplined program advancement to explore a robust pipeline of discovery programs with a focus on addressing the limitations of existing therapies for clinically proven kinase targets in oncology.

Our team combines clinical insights with deep expertise in structure-based drug design and oncology drug development to create new programs where we are able to rapidly advance molecules that are designed to precisely target driver kinases and spare off-targets. This molecular optimization and precise targeting, sometimes by avoiding highly similar off-targets, affords therapies designed to improve the lives of patients with cancer.

hexagon shape
Molecule shape

Our Clinical Trials

Actively recruiting patients in the global Phase 2 with registrational intent

Have you or a loved one been diagnosed with ROS1-positive cancer?

Talk to your doctor today to find out whether you or a loved one may be eligible to receive NVL-520 through the ARROS-1 clinical trial. ARROS-1 is open and enrolling.

For more information, visit www.clinicaltrials.gov (NCT05118789).

View our Expanded Access Policy

Actively recruiting patients in the global Phase 2 with registrational intent

Have you or a loved one been diagnosed with ALK-positive cancer?

Talk to your doctor today to find out whether you or a loved one may be eligible to receive NVL-655 through the ALKOVE-1 clinical trial. ALKOVE-1 is open and enrolling.

For more information, visit www.clinicaltrials.gov (NCT05384626).

View our Expanded Access Policy