A Dose Escalation and Cohort Expansion Study of Subcutaneously-Administered Cytokine ALKS 4230 (Nemvaleukin Alfa) as a Single Agent and in Combination With Anti-PD-1 Antibody (Pembrolizumab) in Subjects With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)

NCT03861793 | Completed Phase 1 FDA Drug

• 1 other identifier: ALKS 4230-001
• Study Type: interventional
• Target: 116
• Locations: 6 countries
• Sites: 48

Brief Summary

This study will characterize the safety and tolerability and identify the recommended Phase 2 dose (RP2D) of subcutaneous (SC) ALKS 4230 as monotherapy and in combination with pembrolizumab.

Conditions

Advanced Solid Tumors

Keywords

Alkermes; IL-2; Interleukin-2; Oncology; Immuno-oncology; Cytokine; ALKS 4230; Pembrolizumab; Keytruda; PD-L1; Solid tumors; Immunotherapy; nemvaleukin alfa; ovarian; Head and Neck; NSCLC; Non small cell lung cancer; lung cancer; Gastric; Gastric Cancer; Gastroesophageal Cancer; Gastroesophageal junction (GEJ) adenocarcinoma; GEJ Cancer; adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A

  Includes AEs that are both serious and drug-related

  From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months

• Number of subjects experiencing AEs that are both serious and drug-related in Part B

  Includes AEs that are both serious and drug-related

  From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months

• Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type.

  Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images

  From time of therapy until the date of first documented tumor progression, assessed up to 24 months

Secondary Outcomes (10)

• Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR)

  From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months

• Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR)

  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 CR/iCR

  Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)

• Duration of response in subjects with PR/iPR

  Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)

• Non-progression for Part B

  Assessed up to 24 months

Study Arms (2)

ALKS 4230

EXPERIMENTAL

Administered via SC injection once every 7 days or once every 21 days at escalating doses

Biological: ALKS 4230

ALKS 4230 + pembrolizumab

EXPERIMENTAL

ALKS 4230 will be administered via SC injection once every 7 or 21 days at escalating doses or at the recommended phase 2 dose and schedule; pembrolizumab will be administered as an intravenous infusion given over 30 minutes; the dose level for pembrolizumab will be 200 mg per the approved label. In December 2020, an RP2D of 3 mg with an administration schedule of q7d was determined for SC ALKS 4230.

Biological: ALKS 4230; Biological: Pembrolizumab

Interventions

ALKS 4230 BIOLOGICAL

SC injection administered in the back of the arm or the abdomen

ALKS 4230; ALKS 4230 + pembrolizumab

Pembrolizumab BIOLOGICAL

Administered as an intravenous (IV) infusion over 30 minutes

Also known as: Keytruda

ALKS 4230 + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• For Phase I the subject has histological or cytological evidence of a solid tumor. For Phase II the subject must have 1 of the specified adult solid tumor types: gastric, ovarian, lung, head and neck.
• Subject must have at least one target lesion based on RECIST
• Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
• Subjects must have adequate liver function
• Subjects must have adequate kidney function
• Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy or surgery
• Subjects who have received radiation therapy must wait at least 4 weeks after their last radiation treatment before enrollment into the study
• Females of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and on Day 1 before the first dose is administered
• Subject will agree to follow contraceptive requirements defined in the protocol
• Additional criteria may apply

You may not qualify if:

• Subject is currently pregnant, planning to become pregnant, or breastfeeding
• Subjects with an active infection or with a fever ≥ 38.5°C within 3 days of the first scheduled day of dosing for Cycle 1
• Subjects with active or symptomatic central nervous system metastases are excluded. Subjects with central nervous system metastases are eligible for the study if the metastases have been treated by surgery and/or radiation therapy, the subject is off corticosteroids for at least 2 weeks, and the subject is neurologically stable
• Subjects with known hypersensitivity to any components of ALKS 4230 or to pembrolizumab or any of its excipients
• Subjects who require pharmacologic doses of systemic corticosteroids are excluded; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted
• Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and/or neuropathy
• Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subjects to cooperate and participate in the study
• The subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B or C, or active tuberculosis, or has a known history of tuberculosis
• Additional criteria may apply

Sponsors & Collaborators

• Mural Oncology, Inc: lead

Study Sites (48)

Mural Oncology Investigational Site

Los Angeles, California, 90025, United States

Location

Mural Oncology Investigational Site

Los Angeles, California, 90211, United States

Location

Mural Oncology Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

Mural Oncology Investigational Site

Atlanta, Georgia, 30322, United States

Location

Mural Oncology Investigational Site

Chicago, Illinois, 60612, United States

Location

Mural Oncology Investigational Site

Bethesda, Maryland, 20817, United States

Location

Mural Oncology Investigational Site

Detroit, Michigan, 48201, United States

Location

Mural Oncology Investigational Site

Saint Paul, Minnesota, 55101, United States

Location

Mural Oncology Investigational Site

Morristown, New Jersey, 07962, United States

Location

Mural Oncology Investigational Site

Buffalo, New York, 14263, United States

Location

Mural Oncology Investigational Site

Huntersville, North Carolina, 28078, United States

Location

Mural Oncology Investigational Site

Cincinnati, Ohio, 45229, United States

Location

Mural Oncology Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

Mural Oncology Investigational Site

Charleston, South Carolina, 29425, United States

Location

Mural Oncology Investigational Site

Houston, Texas, 77030, United States

Location

Mural Oncology Investigational Site

Salt Lake City, Utah, 84119, United States

Location

Mural Oncology Investigational Site

Milwaukee, Wisconsin, 53226, United States

Location

Mural Oncology Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Mural Oncology Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Mural Oncology Investigational Sites

Montreal, Quebec, H2X 0C1, Canada

Location

Mural Oncology Investigational Site

Montreal, Quebec, H3A 3J1, Canada

Location

Mural Oncology Investigational Site

Montreal, Quebec, H3T 1E2, Canada

Location

Mural Oncology Investigational Site

Québec, Quebec, G1R 2J6, Canada

Location

Mural Oncology Investigational Site

Rotterdam, 3000 CA, Netherlands

Location

Mural Oncology Investigational Site

Utrecht, 3508 GA, Netherlands

Location

National Cancer Center

Goyang, 10408, South Korea

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei University Health System - Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, 16247, South Korea

Location

Mural Oncology Investigational Site

Badalona, 08916, Spain

Location

Mural Oncology Investigational Site

Córdoba, 14004, Spain

Location

Mural Oncology Investigational Site

Madrid, 28007, Spain

Location

Mural Oncology Investigational Site

Madrid, 28040, Spain

Location

Mural Oncology Investigational Site

Madrid, 28041, Spain

Location

Mural Oncology Investigational Site

Madrid, 28050, Spain

Location

Mural Oncology Investigational Site

Madrid, 28222, Spain

Location

Mural Oncology Investigational Site

Málaga, 29010, Spain

Location

Mural Oncology Investigational Site

Valencia, 46010, Spain

Location

Mural Oncology Investigational Site

Kaohsiung City, 83301, Taiwan

Location

Mural Oncology Investigational Site

Taichung, 40447, Taiwan

Location

Mural Oncology Investigational Site

Tainan, 704, Taiwan

Location

Mural Oncology Investigational Site

Taipei, 100, Taiwan

Location

Mural Oncology Investigational Site

Taipei, 11217, Taiwan

Location

Mural Oncology Investigational Site

Taipei, 11259, Taiwan

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Stomach Neoplasms; Adenocarcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Mural Oncology Medical Director

  Mural Oncology

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 4, 2019
• Study Start: February 26, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (6); CA (6); US (17); ES (9); NL (2); KR (8)