Nemvaleukin Alfa + Pembrolizumab for Cancer

(ARTISTRY-3 Trial)

Not currently recruiting at 13 trial locations

Overseen By Director Global Clinical Services

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mural Oncology, Inc

Must not be taking: Systemic corticosteroids, Immunomodulatory agents

Disqualifiers: CNS metastases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Each cycle is 14 or 21 days, assessed up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a combination of two treatments, nemvaleukin alfa (a potential new drug also known as ALKS 4230) and pembrolizumab, to assess their effects on certain cancers, such as melanoma and ovarian cancer. Researchers are investigating how these treatments interact with the tumor environment and whether less frequent dosing remains effective. Individuals with certain advanced cancers that have not responded to previous treatments might be suitable candidates. Participants should have a tumor that can be biopsied for the study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must wait at least 4 weeks after your last antineoplastic therapy (cancer treatment) before starting the trial, and you cannot be on certain immunomodulatory agents or systemic corticosteroids above a specific dose.

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

Research has shown that both nemvaleukin alfa and pembrolizumab have been tested for safety in humans. Nemvaleukin alfa, a modified protein, is generally well-tolerated, even by individuals with heart issues. Common side effects include mild to moderate nausea and cytokine release syndrome, an immune system response, which are usually not serious.

Pembrolizumab, also known as Keytruda, has a strong safety record in treating various cancers. A large study involving over 10,000 patients confirmed its consistent safety. The FDA has already approved it for multiple cancers, indicating a well-understood safety profile. Overall, both treatments appear tolerable, with most side effects being mild to moderate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for cancer harness the immune system to attack tumors. But Nemvaleukin Alfa works differently by specifically targeting the tumor microenvironment (TME). This is exciting because it could potentially enhance the immune system's ability to fight cancer without harming healthy cells. Additionally, with less frequent dosing, Nemvaleukin Alfa may offer a more convenient option for patients. Combined with Pembrolizumab, a well-known immunotherapy, this approach could improve outcomes by boosting the immune response even further.

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

Research has shown that nemvaleukin alfa can help reduce tumors when administered intravenously for 5 days in a 21-day cycle. This treatment has proven to be safe and manageable for patients, suggesting it could help shrink tumors. In this trial, some participants will receive nemvaleukin alfa alone, while others will receive it with pembrolizumab. Pembrolizumab has effectively treated various cancers, such as melanoma and other solid tumors. It aids the immune system in attacking cancer cells, potentially leading to longer survival for some patients. Together, these treatments might offer a promising way to fight cancer by enhancing the body's natural defenses. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Monitor

Principal Investigator

Mural Oncology

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including melanoma, lung cancer, and ovarian cancer. Participants must have had 1-3 prior treatments fail or be intolerable. They should have a measurable tumor and good blood, liver, and kidney function. Prior immunotherapy is allowed under specific conditions but no recent steroids or other disqualifying treatments.

Inclusion Criteria

I am a woman who can have children and my pregnancy test is negative.

Additional criteria may apply

My blood counts are within a healthy range.

Exclusion Criteria

I have never received IL-2 or IL-15 protein therapy.

I have active brain metastases.

I have had another type of cancer within the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Nemvaleukin administered via IV infusion daily for 5 consecutive days followed by an off-treatment period. Starting on Cycle 3, Day 1 of each cycle, Pembrolizumab will be administered via IV infusion followed by IV infusion of nemvaleukin.

Each cycle is 14 or 21 days, assessed up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nemvaleukin alfa (ALKS 4230)
• Pembrolizumab

Trial Overview The study tests Nemvaleukin alfa alone or with Pembrolizumab in two groups: one focusing on how the drug affects the tumor environment (single-center), and another on less frequent IV dosing of the drugs (multi-center). It aims to see if these approaches are effective against various solid tumors.

How Is the Trial Designed?

Group I: Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab Experimental Treatment 2 Interventions

This arm will not open for enrollment.

Group II: Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin Experimental Treatment 1 Intervention

Group III: Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab Experimental Treatment 2 Interventions

Nemvaleukin will be administered via Intravenous (IV) infusion given daily for 5 consecutive days followed by an off-treatment period. Starting on Cycle 3, Day 1 of each cycle, Pembrolizumab will be administered via IV infusion followed by IV infusion of nemvaleukin

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

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04592653

Study Details | NCT04592653 | Less Frequent IV Dosing & ... The study will be conducted in 2 cohorts. A single-center design for the tumor microenvironment (TME) cohort (Cohort 1), and a multicenter design for the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12574322/

Less frequent intravenous dosing of nemvaleukin alfa in ... Intravenous (IV) nemvaleukin alfa (nemvaleukin, ALKS 4230) administered daily on days 1-5 in 21‑day cycles demonstrated antitumor activity and manageable safety ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2587

Recommended phase 2 dose (RP2D) of nemvaleukin alfa ... Results: As of Jan 1, 2024, 49 pts have been treated: 17, 13, and 19 in schedules 1, 2, and 3, respectively. No DLTs have been reported. NK and ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A249

results from the phase 1/2 ARTISTRY-3 study Clinical outcomes of ovarian cancer patients treated with ALKS 4230, a novel engineered cytokine, in combination with pembrolizumab: ARTISTRY-1 trial.

5. academic.oup.com academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyaf301/8262864?searchresult=1

Less Frequent Intravenous Dosing of Nemvaleukin Alfa in ... Intravenous (IV) nemvaleukin alfa (nemvaleukin, ALKS 4230) administered daily on days 1-5 in 21‑day cycles demonstrated antitumor activity and manageable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11580269/

Nemvaleukin alfa, a modified interleukin-2 cytokine, as ... The manageable safety profile enables nemvaleukin application in the majority of patients with cancer regardless of their cardiovascular fitness ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2500

Nemvaleukin alfa monotherapy and in combination with ... Safety was consistent with previous reports. In pharmacodynamic studies, nemvaleukin monotherapy induced robust expansion of CD8+ T and NK cells ...

8. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A839

Abstract The most frequent treatment-related AEs (>20%) include cytokine release syndrome and nausea; most events were grade 1–2 (Safety cutoff: April 21 ...

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

Nemvaleukin Alfa Shows Promising Activity in Advanced ... Nemvaleukin alfa (ALKS 4230) was found to be well tolerated while showing positive anti-tumor activity, according to data from the three-part, open-label phase ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02799095

A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on ... Inclusion Criteria: For Part A, the subject has histological or cytological evidence of a solid tumor; for Part B, the subject has a diagnosis of melanoma ...