Less Frequent IV Dosing & Tumor Microenvironment (TME) Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab (ARTISTRY-3)
Study Details
Study Description
Brief Summary
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 less frequent intravenous (IV) dosing cohort (Cohort 2).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab 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 |
Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Names:
Biological: Pembrolizumab
IV infusion over 30 minutes
Other Names:
|
| Experimental: Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin
|
Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Names:
|
| Experimental: Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab
|
Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Names:
Biological: Pembrolizumab
IV infusion over 30 minutes
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) [From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy]
Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies
- Changes in ratios (including T/Treg, CD8+/Treg, CD56+/Treg) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies [From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy]
- Incidence of dose-limiting toxicity (DLT) [From the first dose through end of dose-limiting toxicity observation period (up to 24 months)]
Secondary Outcome Measures
- Proportion of subjects with objective evidence of Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)](CR)/immune CR (iCR) [From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months]
- Duration of response in subjects with Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)] [Time from the first documentation of complete response or partial response to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)]
- Incidence of Adverse Events [Time from first dose of study drug to the end of study (estimated up to 24 months)]
- Incidence of drug-related Serious Adverse Events [Time from first dose of study drug to the end of study (estimated up to 24 months)]
- Incidence of drug-related Adverse Events leading to discontinuation [Time from first dose of study drug to the end of study (estimated up to 24 months)]
- Serum concentrations of ALKS 4230 [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
Concentration data will be summarized by dose level
- Serum will be assayed for the presence of anti-ALKS 4230 antibodies [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
Results will be summarized by dose level
- Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells) [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
- Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on treatment [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
- Serum concentrations of proinflammatory cytokines, including IFNγ, TNF-α, IL-1B, IL-6, IL-10, will be assessed using a multiplex method from initiation of therapy [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
- Changes in absolute numbers of circulating leukocytes [From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months]
Changes in absolute numbers of circulating leukocytes between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically or cytologically confirmed diagnosis of an advanced solid tumor type of cutaneous melanoma, RCC, TNBC, MSS colorectal cancer, MSI-H solid tumors (NOS), or ovarian cancer with at least 1 accessible lesion for biopsy (Cohort 1 TME)
-
Patients must have histologically or cytologically confirmed epithelial tumor of the fallopian tube, peritoneum, or ovaries, cervical cancer, endometrial cancer, non-small cell lung adenocarcinoma, small cell lung cancer, gastric and gastroesophageal junction adenocarcinoma, esophageal cancer (squamous and adeno cell type), pancreatic cancer, biliary tract tumor (including intra- and extrahepatic cholangiocarcinoma, gall bladder, ampullary type), cutaneous melanoma, mucosal melanoma, head and neck squamous cell carcinoma, or metastatic or advanced breast cancer after treatment failure or intolerance of 1 to 3 established indication specific therapies (Cohort 2)
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Patient must have received 1 to 3 prior FDA-approved targeted therapies, failure of adjuvant and neoadjuvant therapy is considered 1 line of treatment
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All patients' baseline biopsies must be taken no more than 3 months before Screening and at least 4 weeks after completion of last antineoplastic therapy
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Patients must have at least 1 lesion that qualifies as a target lesion
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Patients must have adequate hematologic reserve
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Patients must have adequate hepatic and renal function
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For Cohort 1 (TME) and Part A of Cohort 2 (less frequent IV dosing), treatment with prior immunotherapy is permitted unless the patient has previously experienced grade ≥3 autoimmune toxicity or drug-related toxicity requiring discontinuation. Patients in Part B of Cohort 2 (less frequent IV dosing) who received prior anti-PD-(L)1 for at least 3 months may enroll if they had a response of stable disease or better
-
Women of childbearing potential (WOCBP) must have a negative pregnancy test
-
Additional criteria may apply
Exclusion Criteria:
-
Patients with active or symptomatic central nervous system metastases
-
Patients who require pharmacologic doses of systemic corticosteroids (greater than 10 mg of prednisone daily or equivalent)
-
Patients known to be positive for HIV and/or history of hepatitis B, or C infections or is known to be positive for hepatitis B antigen (HBsAg)/hepatitis B virus (HBV) DNA or hepatitis C antibody (Hep C Ab) or RNA.
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Patients with a known additional malignancy within 2 years of the start of Screening
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Patients who have received radiotherapy within the last 4 weeks before start of study treatment
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Patients who have received systemic immunomodulatory agents within 4 weeks or 5 half lives, whichever is shorter, before Cycle 1 Day 1,
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Patients who have received prior IL-2-based or IL-15-based soluble protein therapy at any time in the past are excluded
-
Additional criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alkermes Investigator Site | Grand Rapids | Michigan | United States | 49546 |
| 2 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 3 | Alkermes Investigator Site | West Valley City | Utah | United States | 84119 |
| 4 | Alkermes Investigator Site | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Alkermes, Inc.
Investigators
- Study Director: Sonali Panchabhai, Alkermes, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALKS 4230-003