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

Study Overview
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Brief Summary
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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
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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 Arm 3: Nemvaleukin monotherapy Arm 4: Investigator's choice chemotherapy include one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine.

Official Title
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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)

Conditions
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Platinum-resistant Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Biological: Nemvaleukin and Pembrolizumab Combination
* Biological: Pembrolizumab
* Biological: Nemvaleukin
* Drug: Pegylated Liposomal Doxorubicin (PLD)
* Drug: Paclitaxel
* Drug: Topotecan
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemvaleukin and Pembrolizumab Combination<br> | Biological: Nemvaleukin and Pembrolizumab Combination<br>* 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<br>* Other names: Keytruda;|
| Experimental: Pembrolizumab<br> | Biological: Pembrolizumab<br>* Pembrolizumab: 200 mg; Day 1 of 21-day cycles; IV infusion over 30 minutes<br>* Other names: Keytruda;|
| Experimental: Nemvaleukin<br> | Biological: Nemvaleukin<br>* Nemvaleukin: 6 µg/kg/day; Days 1 through 5 of 21-day cycles; IV infusion over 30 minutes<br>* Other names: ALKS 4230;|
| Active Comparator: Investigator's Choice<br>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. | Drug: Pegylated Liposomal Doxorubicin (PLD)<br>* 40 mg/m2; Day 1 of 28-day cycles; IV infusion; 1 mg/min (Cycle 1); 60 min infusion (Cycles 2+)<br>* Other names: Myocet;Drug: Paclitaxel<br>* 80 mg/m2; Days 1, 8, 15, and 22 of 28-day cycles; IV infusion over 60 min<br>* Other names: Paclitaxel Novaplus;Drug: Topotecan<br>* 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<br>* Other names: Potactasol;Drug: Gemcitabine<br>* 1,000 mg/m2; Days 1 and 8 of 21-day cycles; IV infusion over 30 min<br>* Other names: Infugem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) as assessed by Investigator |  | Up to 1 year | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paclitaxel, PROC, EOC, ALKS 4230, IL-2, Ovarian Cancer, KEYNOTE-C71, Platinum Resistant, Epithelian Ovarian Cancer, Nemvaleukin alfa, Pembrolizumab, ARTISTRY-7, ART-7, pegylated liposoma doxorubicin, PLD, topotecan, gemzar, gemcitabine