What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving ALK inhibitors like NVL-655, often include targeted therapies. Known side effects of ALK inhibitors can include gastrointestinal issues (nausea, vomiting, diarrhea), liver enzyme abnormalities, fatigue, edema, and respiratory symptoms. More severe but less common side effects may include interstitial lung disease, cardiac issues, and severe hepatotoxicity. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several ALK inhibitors for the treatment of solid tumors, particularly non-small cell lung cancer (NSCLC) with ALK rearrangements. These include crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. These drugs target the anaplastic lymphoma kinase (ALK) gene rearrangements, which are present in a subset of NSCLC patients, and have shown significant efficacy in improving progression-free survival and overall response rates. These treatments are similar to NVL-655, which is currently being studied for its safety, tolerability, and antitumor activity in patients with advanced ALK-positive NSCLC and other solid tumors.

What other types of research exist?

Promising alternatives to NVL-655 for solid tumors with ALK rearrangement or mutation include Lorlatinib, Ensartinib, and Brigatinib. Additionally, emerging therapies such as combination treatments with ALK inhibitors and immune checkpoint inhibitors (e.g., Atezolizumab) are being explored in clinical trials and may offer new options in 2024.

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Monoclonal Antibodies

NVL-655 for NSCLC

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

Age ≥18 years

Cohort 2d: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation

Must not have

Major surgery within 4 weeks of the study entry

Ongoing or anticancer therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2-3 years after first patient dosed

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called NVL-655 to see if it is safe and effective for patients with advanced ALK-positive lung cancer and other solid tumors. The drug works by blocking a protein that helps cancer cells grow. The study focuses on patients who have specific genetic changes and may not respond well to standard treatments. Newer treatments have been shown to improve outcomes in ALK-translocated lung cancer compared to older treatments.

Who is the study for?

This trial is for adults with advanced solid tumors, especially non-small cell lung cancer (NSCLC), that have changes in a gene called ALK. Kids over 12 and weighing more than 40 kg can join one part of the study. Participants need to have measurable disease and good organ function but can't be on other cancer treatments or have allergies to NVL-655 components.

What is being tested?

NVL-655 is being tested in two phases: Phase 1 finds the safest dose by slowly increasing it, while Phase 2 tests how well this dose works using measures like tumor shrinkage rate, how long patients respond, survival without disease getting worse, overall survival time, and total benefit rate.

What are the potential side effects?

While specific side effects of NVL-655 are not listed here, similar drugs often cause tiredness, nausea, diarrhea or constipation; blood count changes leading to infection risk; liver or kidney issues; and sometimes allergic reactions during infusion.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My cancer is advanced or has spread, and tests show an ALK gene change.

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My advanced lung cancer has a specific genetic change known as ALK rearrangement.

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My cancer is advanced or has spread, and tests show an ALK gene change.

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My advanced lung cancer has a confirmed ALK gene change.

Exclusion Criteria

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

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

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I am currently receiving treatment for cancer.

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My cancer is driven by a genetic change not related to ALK.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2-3 years after first patient dosed

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2-3 years after first patient dosed

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2-3 years after first patient dosed for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicities (DLTs) (Phase 1)

Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)

Objective Response Rate (ORR) (Phase 2)

+1 more

Secondary study objectives

Area under the curve at the end of the dosing interval (AUCtau) of NVL-655

Area under the curve from time 0 to 24 (AUC0-24) of NVL-655

Area under the curve from time 0 to infinity (AUCinf) of NVL-655

+15 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Group I: Phase 1 dose escalationExperimental Treatment1 Intervention

NVL-655 oral daily dosing

Group II: Cohort 2fExperimental Treatment1 Intervention

Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.

Group III: Cohort 2eExperimental Treatment1 Intervention

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.

Group IV: Cohort 2dExperimental Treatment1 Intervention

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.

Group V: Cohort 2cExperimental Treatment1 Intervention

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.

Group VI: Cohort 2bExperimental Treatment1 Intervention

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.

Group VII: Cohort 2aExperimental Treatment1 Intervention

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.

0 / 8Eligibility 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

The most common treatments for solid tumors include targeted therapies, chemotherapy, and immunotherapy. Targeted therapies, such as ALK inhibitors like NVL-655, work by specifically targeting and inhibiting the activity of the anaplastic lymphoma kinase (ALK) gene rearrangements or mutations, which are known to drive tumor growth in certain cancers like non-small cell lung cancer (NSCLC). This precision in targeting helps to minimize damage to normal cells and reduce side effects compared to traditional chemotherapy. Chemotherapy works by killing rapidly dividing cells but can affect both cancerous and healthy cells, leading to broader side effects. Immunotherapy boosts the body's immune system to recognize and attack cancer cells. For patients with solid tumors, especially those with specific genetic alterations like ALK rearrangements, targeted therapies offer a more effective and personalized treatment option, potentially leading to better outcomes and improved quality of life.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Crizotinib in ALK+ inflammatory myofibroblastic tumors-Current experience and future perspectives.