Less Frequent IV Dosing & Tumor Microenvironment (TME) Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab (ARTISTRY-3)

NCT04592653 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ALKS 4230-003
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 6

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).

Conditions

Advanced Solid Tumor

Keywords

Alkermes; IL-2; Interleukin-2; Oncology; Immuno-oncology; Cytokine; Pembrolizumab; Keytruda; PD-L1; Solid tumors; Immunotherapy; Nemvaleukin

Outcome Measures

Primary Outcomes (3)

• Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells)

  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

  From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy

• 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 Outcomes (11)

• 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)

Study Arms (3)

Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin

EXPERIMENTAL

Biological: Nemvaleukin alfa

Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab

EXPERIMENTAL

This arm will not open for enrollment.

Biological: Nemvaleukin alfa; Biological: Pembrolizumab

Interventions

Nemvaleukin alfa BIOLOGICAL

IV infusion over 30 minutes

Also known as: ALKS 4230

Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab; Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin; Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab

Pembrolizumab BIOLOGICAL

IV infusion over 30 minutes

Also known as: Keytruda

Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab; Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mural Oncology, Inc: lead

Study Sites (6)

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

START Mountain

West Valley City, Utah, 84119, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

CIOCC HM Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Study Officials

• Medical Monitor

  Mural Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: October 19, 2020
• Study Start: September 30, 2020
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 7, 2024

Record last verified: 2024-01

Locations

ES (2); US (4)