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)

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1/2 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-2 (001)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03861793
• Other study ID #: ALKS 4230-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 26, 2019
• Est. completion date: March 1, 2023

Study information

• Verified date: March 2024
• Source: Mural Oncology, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Biological:
• ALKS 4230
SC injection administered in the back of the arm or the abdomen
• Pembrolizumab
Administered as an intravenous (IV) infusion over 30 minutes

Locations

Country	Name	City	State
Canada	Mural Oncology Investigational Site	Edmonton	Alberta
Canada	Mural Oncology Investigational Site	Hamilton	Ontario
Canada	Mural Oncology Investigational Site	Montréal	Quebec
Canada	Mural Oncology Investigational Site	Montréal	Quebec
Canada	Mural Oncology Investigational Sites	Montréal	Quebec
Canada	Mural Oncology Investigational Site	Québec	Quebec
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea St. Vincent's Hospital	Suwon
Netherlands	Mural Oncology Investigational Site	Rotterdam
Netherlands	Mural Oncology Investigational Site	Utrecht
Spain	Mural Oncology Investigational Site	Badalona
Spain	Mural Oncology Investigational Site	Córdoba
Spain	Mural Oncology Investigational Site	Madrid
Spain	Mural Oncology Investigational Site	Madrid
Spain	Mural Oncology Investigational Site	Madrid
Spain	Mural Oncology Investigational Site	Madrid
Spain	Mural Oncology Investigational Site	Madrid
Spain	Mural Oncology Investigational Site	Málaga
Spain	Mural Oncology Investigational Site	Valencia
Taiwan	Mural Oncology Investigational Site	Kaohsiung
Taiwan	Mural Oncology Investigational Site	Taichung
Taiwan	Mural Oncology Investigational Site	Tainan
Taiwan	Mural Oncology Investigational Site	Taipei
Taiwan	Mural Oncology Investigational Site	Taipei
Taiwan	Mural Oncology Investigational Site	Taipei
United States	Mural Oncology Investigational Site	Atlanta	Georgia
United States	Mural Oncology Investigational Site	Bethesda	Maryland
United States	Mural Oncology Investigational Site	Buffalo	New York
United States	Mural Oncology Investigational Site	Charleston	South Carolina
United States	Mural Oncology Investigational Site	Chicago	Illinois
United States	Mural Oncology Investigational Site	Cincinnati	Ohio
United States	Mural Oncology Investigational Site	Detroit	Michigan
United States	Mural Oncology Investigational Site	Houston	Texas
United States	Mural Oncology Investigational Site	Huntersville	North Carolina
United States	Mural Oncology Investigational Site	Los Angeles	California
United States	Mural Oncology Investigational Site	Los Angeles	California
United States	Mural Oncology Investigational Site	Milwaukee	Wisconsin
United States	Mural Oncology Investigational Site	Morristown	New Jersey
United States	Mural Oncology Investigational Site	Philadelphia	Pennsylvania
United States	Mural Oncology Investigational Site	Saint Paul	Minnesota
United States	Mural Oncology Investigational Site	Salt Lake City	Utah
United States	Mural Oncology Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Mural Oncology, Inc

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR)	Overall response rate (ORR) will be based on investigator review of radiographic or photographic images	From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
Secondary	Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR)	ORR will be based on investigator review of radiographic or photographic images	From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
Secondary	Duration of response in subjects with CR/iCR	CR/iCR duration	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)
Secondary	Duration of response in subjects with PR/iPR	PR/iPR duration	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)
Secondary	Non-progression for Part B	Time from first dose of SC ALKS 4230 to the time of progression or death	Assessed up to 24 months
Secondary	Overall survival for Part B	Time from first dose of SC ALKS 4230 to the time of death	Assessed up to 24 months
Secondary	Serum concentrations of ALKS 4230 will be determined at various time points	Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level	From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
Secondary	Serum will be assayed for the presence of anti-ALKS 4230 antibodies	Results will be summarized by dose level	From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
Secondary	Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points	Results will be summarized by dose level	From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
Secondary	Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points	Results will be summarized by dose level	From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months