Nemvaleukin Alfa + Pembrolizumab for Cancer

(ARTISTRY-3 Trial)

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

78 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves two ways of treating patients with tumors. One method focuses on the tumor environment, and the other uses a different dosing schedule. The goal is to see which method works better.

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.

What data supports the effectiveness of the drug Nemvaleukin Alfa + Pembrolizumab for cancer?

Pembrolizumab, one of the drugs in the treatment, has shown effectiveness in treating various cancers like melanoma and non-small cell lung cancer by helping the immune system attack cancer cells. It has been approved for use in these cancers due to its ability to improve survival rates compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Nemvaleukin Alfa and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been associated with some immune-related side effects, including a rare risk of developing type 1 diabetes and other immune system reactions like inflammation of the lungs, liver, and thyroid. Common side effects include fatigue, cough, nausea, and skin rash. While these findings are specific to Pembrolizumab, they provide insight into potential safety considerations for its use in combination with other treatments. ^{1 2 5 6 7}

What makes the drug combination of Nemvaleukin Alfa and Pembrolizumab unique for cancer treatment?

This drug combination is unique because it combines Nemvaleukin Alfa, which is designed to selectively activate immune cells, with Pembrolizumab, a PD-1 inhibitor that helps the immune system recognize and attack cancer cells. This dual approach aims to enhance the body's immune response against cancer more effectively than using either drug alone. ^{1 3 4 6 8}

Research Team

Medical Monitor

Principal Investigator

Mural Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

5. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]