Phase 3 Study of Nemvaleukin Alfa in Combination With Pembrolizumab in Patients With Platinum-Resistant Epithelial Ovarian Cancer (ARTISTRY-7) (ARTISTRY-7)

• ClinicalTrials.gov Identifier: NCT05092360
• Recruitment Status: Recruiting
• First Posted: October 25, 2021
• Last Update Posted: April 23, 2024
• Sponsor: Mural Oncology, Inc
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Mural Oncology, Inc

Tracking Information

• First Submitted Date: October 13, 2021
• First Posted Date: October 25, 2021
• Last Update Posted Date: April 23, 2024
• Actual Study Start Date: January 10, 2022
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 19, 2024): Overall Survival (OS) [ Time Frame: Up to 3 years ]
• Original Primary Outcome Measures (submitted: October 13, 2021): Progression-free survival (PFS) as assessed by Investigator [ Time Frame: Up to 1 year ]

Current Secondary Outcome Measures (submitted: April 19, 2024)

• Objective response rate as assessed by Investigator [ Time Frame: Up to 1 year ]
• Disease Control Rate (DCR) as assessed by Investigator [ Time Frame: Up to 1 year ]
• Duration of Response (DOR) as assessed by Investigator [ Time Frame: Up to 1 year ]
• Time to Response (TTR) as assessed by Investigator [ Time Frame: Up to 18-24 weeks ]
• Cancer antigen (CA)-125 response as defined by the Gynecologic Cancer InterGroup (GCIG) [ Time Frame: Up to 1 year ]
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 3 years ]
• Progression-free survival (PFS) as assessed by Investigator [ Time Frame: Up to 1 year ]

Original Secondary Outcome Measures (submitted: October 13, 2021)

• Objective response rate as assessed by Investigator [ Time Frame: Up to 1 year ]
• Overall Survival Rate [ Time Frame: Up to 3 years ]
• Disease Control Rate (DCR) as assessed by Investigator [ Time Frame: Up to 1 year ]
• Duration of Response (DOR) as assessed by Investigator [ Time Frame: Up to 1 year ]
• Time to Response (TTR) as assessed by Investigator [ Time Frame: Up to 18-24 weeks ]
• Cancer antigen (CA)-125 response as defined by the Gynecologic Cancer InterGroup (GCIG) [ Time Frame: Up to 1 year ]
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study of Nemvaleukin Alfa in Combination With Pembrolizumab in Patients With Platinum-Resistant Epithelial Ovarian Cancer (ARTISTRY-7)
• Official Title: A Phase 3, Multicenter, Open-Label, Randomized Study of Nemvaleukin Alfa in Combination With Pembrolizumab Versus Investigator's Choice Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARTISTRY-7)
• Brief Summary: 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.

Detailed Description

Patients will be centrally allocated in a randomized fashion (3:1:1:3) to receive either:

Arm 1: Nemvaleukin and pembrolizumab combination therapy Arm 2: Pembrolizumab monotherapy (enrollment completed) Arm 3: Nemvaleukin monotherapy (enrollment completed) Arm 4: Investigator's choice chemotherapy include one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Platinum-resistant Ovarian Cancer
• Fallopian Tube Cancer
• Primary Peritoneal Cancer

Intervention

• Biological: Nemvaleukin and Pembrolizumab Combination
  Nemvaleukin: 6 µg/kg/day; Days 1 through 5 of 21-day cycles; IV infusion over 30 minutes and Pembrolizumab: 200 mg; Day 1 of 21-day cycles; IV infusion over 30 minutes
  Other Names:

  • Nemvaleukin alfa
  • ALKS 4230
  • Keytruda
• Biological: Pembrolizumab
  Pembrolizumab: 200 mg; Day 1 of 21-day cycles; IV infusion over 30 minutes
  Other Name: Keytruda
• Biological: Nemvaleukin
  Nemvaleukin: 6 µg/kg/day; Days 1 through 5 of 21-day cycles; IV infusion over 30 minutes
  Other Names:

  • Nemvaleukin alfa
  • ALKS 4230
• Drug: Pegylated Liposomal Doxorubicin (PLD)
  40 mg/m2; Day 1 of 28-day cycles; IV infusion; 1 mg/min (Cycle 1); 60 min infusion (Cycles 2+)
  Other Names:

  • PLD- CAELYX
  • DOXIL
  • LIPODOX
  • Myocet
• Drug: Paclitaxel
  80 mg/m2; Days 1, 8, 15, and 22 of 28-day cycles; IV infusion over 60 min
  Other Names:

  • Nov-Onxol
  • Taxol
  • Onxol
  • Paclitaxel Novaplus
• Drug: Topotecan
  4 mg/m2; Days 1, 8, and 15 of 28-day cycles; or 1.25 mg/m2, Days 1 through 5 of 21-day cycles; IV infusion over 30 min
  Other Names:

  • Hycamtin
  • Potactasol
• Drug: Gemcitabine
  1,000 mg/m2; Days 1 and 8 of 21-day cycles; IV infusion over 30 min
  Other Names:

  • Gemzar
  • Infugem

Study Arms

• Experimental: Nemvaleukin and Pembrolizumab Combination
  Intervention: Biological: Nemvaleukin and Pembrolizumab Combination
• Experimental: Pembrolizumab (enrollment completed)
  Intervention: Biological: Pembrolizumab
• Experimental: Nemvaleukin (enrollment completed)
  Intervention: Biological: Nemvaleukin
• Active Comparator: Investigator's Choice
  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.
  Interventions:

  • Drug: Pegylated Liposomal Doxorubicin (PLD)
  • Drug: Paclitaxel
  • Drug: Topotecan
  • Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 19, 2024): 448
• Original Estimated Enrollment (submitted: October 13, 2021): 376
• Estimated Study Completion Date: May 2027
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient is female and ≥18 years of age.
• Patient has histologically confirmed diagnosis of EOC (ie, high-grade serous, endometrioid of any grade, clear cell), fallopian tube cancer, or primary peritoneal cancer.
• Patient has platinum-resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy beyond first-line setting (resistant) or lack of response or disease progression while receiving the most recent platinum-based therapy (refractory). Patient must have progressed radiographically on or after their most recent line of anticancer therapy.
• Patient must have received at least 1 prior line of systemic anticancer therapy in the platinum sensitive setting, and no more than 5 prior lines of systemic anticancer therapy in the platinum-resistant setting. Patient must have received at least 1 line of therapy containing bevacizumab.
• Patient has at least one measurable lesion that qualifies as a target lesion based on RECISTv1.1.
• Patient is willing to undergo a pre-treatment tumor biopsy or provide qualifying archival tumor tissue.

Exclusion Criteria:

• Patient has primary platinum-refractory disease or primary platinum resistance, defined as disease progression during first-line platinum-based therapy (refractory) or disease progression <3 months after completion of first-line platinum-based therapy (resistant).
• Patient has histologically confirmed diagnosis of EOC with mucinous or carcinosarcoma subtype.
• Patient has nonepithelial tumor (eg, germline or stromal cell tumor) or ovarian tumor with low malignant potential (ie, borderline or low-grade serous tumor).
• Patient requires fluid drainage (eg, paracentesis, thoracentesis, pericardiocentesis) of ≥500 mL within 4 weeks of first dose of study drug.
• Patient has received prior IL-2-based or IL-15-based cytokine therapy; patient has had exposure, including intralesional, to IL-12 or analogs thereof.
• Patient has prior exposure to any anti-PD1/PD-L1 therapy.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Senior Direct, Global Clinical Services; 781-614-0100 (US Only); clinicaltrials@muraloncology.com

• Listed Location Countries: Australia, Austria, Belgium, Canada, Czechia, France, Germany, Israel, Italy, Korea, Republic of, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05092360
• Other Study ID Numbers: ALKS 4230-007; GOG-3063 ( Other Identifier: The GOG Foundation ); ENGOT-OV68 ( Other Identifier: European Network Gynaecological Oncological Trial groups ); KEYNOTE-C71 ( Other Identifier: Merck )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Mural Oncology, Inc
• Original Responsible Party: Alkermes, Inc.
• Current Study Sponsor: Mural Oncology, Inc
• Original Study Sponsor: Alkermes, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Mural Oncology Medical Monitor; Mural Oncology, Inc

• PRS Account: Mural Oncology, Inc
• Verification Date: April 2024