What side effects are associated with this type of intervention?

Common side effects of targeted therapies for solid tumors, such as those similar to NVL-520 for ROS1-positive tumors, include gastrointestinal issues (nausea, diarrhea), skin reactions (rash, pruritus), fatigue, and liver function abnormalities. More severe but less common side effects may include pneumonitis, hypertension, and cardiac issues. These side effects are generally more tolerable compared to traditional chemotherapy but still require careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of ROS1-positive solid tumors, particularly non-small cell lung cancer (NSCLC). Crizotinib was the first ROS1 inhibitor approved for ROS1-positive NSCLC. Later, entrectinib was also approved for ROS1-positive NSCLC, offering an alternative for patients. These drugs work by targeting the ROS1 gene rearrangement, similar to the investigational drug NVL-520 being studied for its safety, tolerability, and antitumor activity in ROS1-positive tumors.

What other types of research exist?

Promising alternatives to NVL-520 for ROS1-positive solid tumors include: 1) Bevacizumab, an anti-VEGF monoclonal antibody, which has shown efficacy in various solid tumors including NSCLC. 2) Lapatinib, a dual tyrosine kinase inhibitor, which has been studied in neurofibromatosis type 2 and progressive vestibular schwannomas. 3) Everolimus, an mTOR inhibitor, which has demonstrated activity in neurofibromatosis type 2 and other solid tumors. These therapies have shown potential in clinical trials and could be considered as alternatives in 2024.

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ROS1 Inhibitor

NVL-520 for ROS1-Positive Solid Tumors

Phase 1 & 2

Recruiting

Research Sponsored by Nuvalent Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement for Phase 1

Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement for Cohorts 2a, 2b, 2c, and 2d in Phase 2

Must not have

Patient's cancer has a known oncogenic driver alteration other than ROS1

Known allergy/hypersensitivity to excipients of NVL-520

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2-3 years after first patient dosed.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests NVL-520, a new drug, for safety and effectiveness in patients with advanced ROS1-positive cancers. It targets those who haven't responded well to other treatments by blocking a protein that helps cancer cells grow. NVL-520 is being tested for its effectiveness in treating advanced ROS1-positive cancers, a targetable mutation in non-small cell lung cancer (NSCLC) that has seen various treatments like crizotinib and entrectinib.

Who is the study for?

This trial is for adults with advanced solid tumors, especially non-small cell lung cancer (NSCLC), that have a specific genetic change called ROS1 rearrangement. Patients should have tried other cancer treatments unless they're in one special group. They need to be healthy enough overall and not currently on another clinical study or recent major surgery.

What is being tested?

NVL-520 is being tested to see how safe it is and what dose works best against these cancers. The first phase figures out the right dose; the second checks how well it shrinks tumors using independent reviews, also looking at survival times and other health benefits.

What are the potential side effects?

Possible side effects of NVL-520 aren't detailed here but typically include reactions where the drug enters the body, changes in blood tests reflecting organ function, fatigue, nausea, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My advanced cancer has a confirmed ROS1 rearrangement.

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My advanced lung cancer is confirmed to have a ROS1 rearrangement.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer is driven by a specific genetic change, not ROS1.

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I am allergic to ingredients in NVL-520.

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I am currently receiving treatment for cancer.

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I have not had major surgery in the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ within 28 days of last patient dosed during dose escalation.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~within 28 days of last patient dosed during dose escalation.

This trial's timeline: 3 weeks for screening, Varies for treatment, and within 28 days of last patient dosed during dose escalation. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD) (Phase 1)

Objective Response Rate (ORR) (Phase 2)

Recommended Phase 2 Dose (RP2D)

Secondary study objectives

Area under the curve at the end of the dosing interval (AUCtau) of NVL-520

Area under the curve from time 0 to 24 (AUC0-24) of NVL-520

Area under the curve from time 0 to infinity (AUCinf) of NVL-520

+18 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase 1 dose escalationExperimental Treatment1 Intervention

NVL-520 oral daily dosing

Group II: Cohort 2eExperimental Treatment1 Intervention

ROS1+ solid tumor and progressed on any prior therapy

Group III: Cohort 2dExperimental Treatment1 Intervention

ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy

Group IV: Cohort 2cExperimental Treatment1 Intervention

ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy

Group V: Cohort 2bExperimental Treatment1 Intervention

ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy

Group VI: Cohort 2aExperimental Treatment1 Intervention

ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Targeted therapies, like NVL-520, work by specifically targeting genetic mutations or markers present in cancer cells, such as ROS1 rearrangements in solid tumors. This precision allows for the destruction of cancer cells while minimizing damage to normal cells, leading to potentially fewer side effects and better outcomes compared to traditional chemotherapy. For patients with solid tumors, understanding these mechanisms is important as it highlights the potential for more effective and personalized treatment options.

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