Clinical and Immunologic Activity of Nemvaleukin Alfa With Less Frequent IV Dosing Schedule as Monotherapy and in Combination With Pembrolizumab and Impact on Tumor Microenvironment in Solid Tumor Patients - ARTISTRY-3
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Study Summary
To evaluate the effects of ALKS 4230 on the immune cell repertoire, including changes in density and ratio of immune cells, within the tumor microenvironment.
To investigate the effects of nemvaleukin as monotherapy and in combination with pembrolizumab on the TME in pts with advanced solid tumors, and in an additional cohort (Cohort 2), to further assess a less frequent IV dosing schedule for nemvaleukin.
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).
Cohort 2 will initially assess safety and tolerability of nemvaleukin at 1 dose per 21-day cycle.
Cohort 1 (TME)
To evaluate the effects of nemvaleukin alfa (‘nemvaleukin,’ ‘ALKS 4230’) monotherapy on the TME of a variety of advanced, malignant solid tumors
Cohort 2 (Less Frequent IV Dosing)
To investigate the safety and tolerability of less frequent IV dosing schedules of nemvaleukin to identify and determine a recommended phase 2 dose (RP2D) of nemvaleukin monotherapy
To determine the maximum tolerated dose (MTD) of nemvaleukin monotherapy and in combination with pembrolizumab
To evaluate less-frequent IV nemvaleukin dosing in advanced solid tumors.
Dose-escalation decisions were based on predefined safety parameters of dose-limiting toxicity (DLT) criteria evaluated during cycle 1. Pharmacodynamic assessments included absolute counts of CD8+ T, NK, and Treg cells (cells/μL) by flow cytometry at baseline and in the first 2 cycles.
To report modulation of the TME in ovarian cancer and mucosal melanoma patients dosed with 3 different schedules in ARTISTRY-3.
We performed deep immune profiling using a 14-marker multiplex immunofluorescence panel encompassing various activation states of NK, CD8+ T, CD4+ T, and Treg cells, plasma cells, macrophages, and tumor markers. CD8/NK:Treg densities in whole tissue from all subjects and immune densities in distinct TME regions along with spatial analytics (nearest neighbor distance, neighborhood analysis) from 4 of 5 subjects are reported here.
- 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)
- Patient must have received 1 to 3 prior FDA-approved targeted therapies, failure of adjuvant and neoadjuvant therapy is considered 1 line of treatment
- 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
- Patients must have at least 1 lesion that qualifies as a target lesion
- Patients must have adequate hematologic reserve
- Patients must have adequate hepatic and renal function
- 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
- For Cohort 1 (TME), patients who have received prior anti-PD-1 directed therapy must wait at least 4 weeks from last dose of such therapy before the Screening biopsy is collected
- Women of childbearing potential (WOCBP) must have a negative pregnancy test
- Additional criteria may apply
- Eligible patients with select solid tumors must have exhausted standard-of-care therapies.
- 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.
- Patients with a known additional malignancy within 2 years of the start of Screening
- Patients who have received radiotherapy within the last 4 weeks before start of study treatment
- Patients who have received systemic immunomodulatory agents within 4 weeks or 5 half lives, whichever is shorter, before Cycle 1 Day 1,
- 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
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