Nemvaleukin Alfa for Melanoma

(ARTISTRY-6 Trial)

No longer recruiting at 128 trial locations

Overseen By Mural Oncology Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mural Oncology, Inc

Must be taking: Anti-PD-L1 therapy

Must not be taking: Systemic corticosteroids, IL-2 therapy

Disqualifiers: Uveal melanoma, Pregnancy, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Nemvaleukin Alfa for individuals with advanced melanoma that cannot be surgically removed or has metastasized. The trial aims to evaluate the treatment's effectiveness against cancer, its safety, and how the body processes it. Participants are grouped based on melanoma type (skin or mucosal) and previous treatments. Eligible participants must have certain types of melanoma, possibly have undergone previous cancer treatments, and still have measurable disease. They should also not have received specific prior therapies. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids (more than 10 mg of prednisone daily or equivalent), you may need to adjust your dosage. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Nemvaleukin Alfa, used alone or with pembrolizumab, has been generally safe in previous studies. Side effects were usually mild and manageable. In studies involving melanoma patients, even those with extensive prior treatments, Nemvaleukin Alfa was well-tolerated. This treatment has been tested in both skin-related and moist tissue-related melanoma, demonstrating a good safety record. Evidence so far suggests that Nemvaleukin Alfa is relatively safe for these patients, making it a potential option for those considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for melanoma?

Unlike the standard treatments for melanoma, which often include drugs like nivolumab or ipilimumab, Nemvaleukin Alfa targets a different pathway. It works by selectively activating immune cells to attack the cancer, potentially improving the immune response against melanoma. Researchers are excited because it can be administered in both intravenous and subcutaneous forms, offering flexibility and convenience in dosing. This approach could enhance treatment effectiveness and reduce side effects compared to current therapies.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research has shown that Nemvaleukin Alfa may help treat advanced melanoma, a serious type of skin cancer. In this trial, some participants will receive Nemvaleukin Alfa alone, while others will receive it with pembrolizumab, an immunotherapy that aids the immune system in fighting cancer. One study found that 13% of patients responded well to the treatment, with some even experiencing complete tumor disappearance. The treatment appears safe and manageable, even for patients who have tried many other treatments. These findings suggest that Nemvaleukin Alfa could be a valuable option for those with difficult-to-treat melanoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Mural Oncology Medical Monitor

Principal Investigator

Mural Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced cutaneous or mucosal melanoma who've had prior anti-PD-[L]1 therapy, possibly with anti-CTLA-4 therapy, and at most one other systemic cancer treatment. They should be in good physical condition (ECOG status of 0 or 1), have a life expectancy over three months, measurable disease not recently treated by radiation or biopsy, and stable disease after previous treatments.

Inclusion Criteria

You have advanced skin or mucosal melanoma that cannot be removed by surgery.

My cancer has a BRAF mutation; I may or may not have had targeted therapy.

I can care for myself and doctors expect me to live for at least 3 more months.

Exclusion Criteria

I have never stopped immunotherapy because of side effects.

Patient has known or suspected hypersensitivity to any components of nemvaleukin

I have had a transplant of an organ, stem cells, or bone marrow that was not my own.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nemvaleukin Alfa monotherapy or in combination with Pembrolizumab for advanced melanoma

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nemvaleukin Alfa

Trial Overview The study tests Nemvaleukin Alfa's effectiveness against advanced melanoma post anti-PD-[L]1 therapy. It explores different administration methods: subcutaneous injection, intravenous infusion, and less frequent dosing intravenously to evaluate tumor response and drug safety.

How Is the Trial Designed?

Group I: Advanced mucosal melanoma with IV Dosing (Cohort 2) Experimental Treatment 1 Intervention

Patients with unresectable and/or metastatic mucosal melanoma

Group II: Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4) Experimental Treatment 2 Interventions

Patients with unresectable and/or metastatic cutaneous melanoma. Patients must not have received prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant and/or neoadjuvant PD-\[L\]1 treatments are allowed if there is at least 6 months between the last dose and date of recurrence.

Group III: Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3) Experimental Treatment 1 Intervention

Patients with unresectable and/or metastatic cutaneous melanoma

Group IV: Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1) Experimental Treatment 1 Intervention

Patients with unresectable and/or metastatic cutaneous melanoma

Who Is Running the Clinical Trial?

Mural Oncology, Inc

Lead Sponsor

Trials

6

Recruited

1,100+

Alkermes, Inc.

Lead Sponsor

Trials

118

Recruited

27,200+

Richard Pops

Alkermes, Inc.

Chief Executive Officer since 1991

BA in Economics from Stanford University

Dr. Craig Hopkinson

Alkermes, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

Nemvaleukin alfa, an engineered cytokine, shows promise in treating solid tumors, achieving overall response rates of 13% in advanced melanoma and 18.2% in advanced renal cell carcinoma when used alone.

In combination with pembrolizumab, nemvaleukin alfa resulted in a response rate of 16.1% across various solid tumor types, suggesting it may enhance the effectiveness of existing cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential IL2 Substitute Shrinks Solid Tumors. [2022]

Nemvaleukin alfa selectively expands immune effector cells, such as CD8+ T cells and natural killer (NK) cells, while minimally affecting immunosuppressive regulatory T cells, indicating its potential as an effective cancer immunotherapy.

Subcutaneous administration of nemvaleukin provides similar systemic exposure and immunostimulatory effects as intravenous dosing, suggesting it could be a more practical option for patients in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamic Effects of Nemvaleukin Alfa, a Selective Agonist of the Intermediate-Affinity IL-2 Receptor, in Cynomolgus Monkeys. Lopes, JE., Sun, L., Flick, HL., et al.[2021]

Aldesleukin (recombinant IL-2) has shown modest efficacy in treating metastatic melanoma, with response rates up to 56% in combination therapies, but median survival times remain around 10 to 11 months, indicating limited long-term benefits.

The administration methods of aldesleukin have evolved to reduce toxicity, with continuous intravenous infusion and subcutaneous options leading to fewer severe adverse events, but further studies are needed to fully understand its risk/benefit profile compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldesleukin (recombinant interleukin-2). Noble, S., Goa, KL.[2022]

The combination of encorafenib (ENC) and binimetinib (BIN) was found to be cost-effective compared to cobimetinib (COB) and vemurafenib (VEM) only at a very high willingness-to-pay threshold of $573,000 per quality-adjusted life year (QALY).

The combination of dabrafenib (DAB) and trametinib (TRA) was determined to be the most optimal treatment option for BRAF-mutated advanced melanoma, dominating the COB + VEM combination in terms of cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. Halloush, S., Alkhatib, NS., Almutairi, AR., et al.[2023]

Nemvaleukin alfa is a new cytokine that aims to enhance the effectiveness of interleukin-2 (IL-2) while reducing its toxicity, specifically targeting CD8+ T cells and natural killer cells, which are important for fighting cancer.

The ongoing phase III ARTISTRY-7 trial is evaluating the safety and efficacy of nemvaleukin combined with pembrolizumab compared to standard chemotherapy in patients with platinum-resistant ovarian cancer, with the main goal of improving progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer. Herzog, TJ., Hays, JL., Barlin, JN., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04830124

Study Details | NCT04830124 | Nemvaleukin Alfa ... Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4). Patients with unresectable and/or metastatic cutaneous melanoma ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40759440/

results from the phase 1/2 non-randomized ARTISTRY-1 trial Nemvaleukin alfa (nemvaleukin, ALKS 4230) demonstrated manageable safety and antitumor activity, alone and in combination with pembrolizumab, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12323519/

Nemvaleukin alfa monotherapy in patients with advanced ... We report in-depth antitumor activity, safety, pharmacokinetics, and pharmacodynamics of nemvaleukin monotherapy at the recommended phase 2 dose ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04592653

Study Details | NCT04592653 | Less Frequent IV Dosing & ... Patients must have histologically or cytologically confirmed diagnosis of an advanced solid tumor type of cutaneous melanoma, RCC, TNBC, MSS colorectal cancer, ...

5. cancernetwork.com cancernetwork.com/view/nemvaleukin-alfa-shows-promising-activity-in-advanced-solid-tumors

Nemvaleukin Alfa Shows Promising Activity in Advanced ... Per efficacy, there were 19 confirmed overall responses (13%; 95% CI, 8%-20%) among 144 patients. Of them, 5 (4%) were complete responses, and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04830124

Study Details | NCT04830124 | Nemvaleukin Alfa ... This study observes the antitumor activity, safety, tolerability, PK, and pharmacodynamics in patients with inoperable and/or metastatic melanoma.

7. synapse.patsnap.com synapse.patsnap.com/drug/972eb6e62b274e65b6a388c28de0a78b

Nemvaleukin Alfa - Drug Targets, Indications, Patents Nemvaleukin alfa (nemvaleukin, ALKS 4230) demonstrated manageable safety and antitumor activity, alone and in combination with pembrolizumab, ...

8. targetedonc.com targetedonc.com/view/nemvaleukin-shows-durable-antitumor-activity-in-melanoma-rcc

Nemvaleukin Shows Durable Antitumor Activity in ... Nemvaleukin alfa shows promising antitumor activity in advanced melanoma and renal cell carcinoma, with manageable safety in heavily pretreated ...