Nemvaleukin + Pembrolizumab for Ovarian Cancer

(ARTISTRY-7 Trial)

Recruiting at 280 trial locations

Overseen By Senior Direct, Global Clinical Services

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Alkermes, Inc.

Must not be taking: IL-2, IL-15, Anti-PD1/PD-L1

Disqualifiers: Primary platinum-refractory, Mucinous subtype, Others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

456 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, multicenter, open-label, randomized study of nemvaleukin in combination with pembrolizumab versus protocol-specific Investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Nemvaleukin and Pembrolizumab for ovarian cancer?

Research shows that pembrolizumab, a part of this drug combination, has shown some effectiveness in treating advanced ovarian cancer, especially in patients whose tumors express PD-L1, a protein that helps cancer cells hide from the immune system. Additionally, pembrolizumab has been used in combination with other drugs for platinum-resistant ovarian cancer, indicating potential benefits in similar settings. ^{1 2 3 4 5}

Is the combination of Nemvaleukin and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been studied in various conditions, including ovarian cancer, and has shown a safety profile consistent with its use in humans. In nonhuman primate studies, no significant toxic effects were observed, and clinical trials in humans have demonstrated its safety in treating different types of cancer. ^{1 2 3 4 6}

How is the drug combination of Nemvaleukin and Pembrolizumab unique for treating ovarian cancer?

The combination of Nemvaleukin and Pembrolizumab is unique because it combines an immune-activating agent (Nemvaleukin) with a PD-1 inhibitor (Pembrolizumab) to enhance the body's immune response against cancer cells, potentially offering a novel approach for ovarian cancer treatment compared to traditional chemotherapy. ^{1 2 4 6 7}

Research Team

Mural Oncology Medical Monitor

Principal Investigator

Mural Oncology, Inc

Eligibility Criteria

This trial is for women over 18 with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. They must have seen their disease progress after recent therapy and received at least one line of bevacizumab-containing treatment. Excluded are those with certain subtypes of EOC, prior anti-PD1/PD-L1 therapy exposure, non-epithelial tumors, or significant fluid drainage needs.

Inclusion Criteria

I am willing to have a biopsy or provide previous biopsy samples.

My cancer got worse or didn't respond to platinum therapy within 6 months.

I've had 1-5 treatments for cancer that didn't respond well to platinum, including one with bevacizumab.

Exclusion Criteria

My ovarian cancer is of the mucinous or carcinosarcoma type.

My ovarian tumor is non-epithelial or has low malignant potential.

I have been treated with anti-PD1/PD-L1 therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nemvaleukin and pembrolizumab combination therapy, pembrolizumab monotherapy, nemvaleukin monotherapy, or investigator's choice chemotherapy

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Nemvaleukin
• Pembrolizumab

Trial Overview The study compares nemvaleukin alfa combined with pembrolizumab against a choice chemotherapy in patients who've had limited success with platinum-based treatments. It's an open-label Phase 3 trial where participants are randomly assigned to the treatment groups.

Participant Groups

Group I: Pembrolizumab (enrollment completed) Experimental Treatment 1 Intervention

Group II: Nemvaleukin and Pembrolizumab Combination Experimental Treatment 1 Intervention

Group III: Nemvaleukin (enrollment completed) Experimental Treatment 1 Intervention

Group IV: Investigator's Choice Active Control 4 Interventions

Options for protocol-specific Investigator's choice chemotherapy include one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine. The Investigator will pre-select the Investigator's choice treatment before the randomization of each patient.

Who Is Running the Clinical Trial?

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

Mural Oncology, Inc

Lead Sponsor

Trials

6

Recruited

1,100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

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) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

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 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]

References

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

3. 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]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]

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

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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