Clinical trial NCT03861793: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Mural Oncology, Inc
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A
timeFrame: From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months
measure: Number of subjects experiencing AEs that are both serious and drug-related in Part B
timeFrame: From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months
measure: Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type.
timeFrame: From time of therapy until the date of first documented tumor progression, assessed up to 24 months
Secondary outcomes:
measure: Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR)
timeFrame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
measure: Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR)
timeFrame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
measure: Duration of response in subjects with CR/iCR
timeFrame: 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)
measure: Duration of response in subjects with PR/iPR
timeFrame: 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)
measure: Non-progression for Part B
timeFrame: Assessed up to 24 months
measure: Overall survival for Part B
timeFrame: Assessed up to 24 months
measure: Serum concentrations of ALKS 4230 will be determined at various time points
timeFrame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
measure: Serum will be assayed for the presence of anti-ALKS 4230 antibodies
timeFrame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
measure: Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points
timeFrame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
measure: Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points
timeFrame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mural Oncology Investigational Site
state: California
city: Los Angeles
country: United States
facility: Mural Oncology Investigational Site
state: California
city: Washington
country: United States
facility: Mural Oncology Investigational Site
state: District of Columbia
city: Atlanta
country: United States
facility: Mural Oncology Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Mural Oncology Investigational Site
state: Illinois
city: Bethesda
country: United States
facility: Mural Oncology Investigational Site
state: Maryland
city: Detroit
country: United States
facility: Mural Oncology Investigational Site
state: Michigan
city: Saint Paul
country: United States
facility: Mural Oncology Investigational Site
state: Minnesota
city: Morristown
country: United States
facility: Mural Oncology Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: Mural Oncology Investigational Site
state: New York
city: Huntersville
country: United States
facility: Mural Oncology Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Mural Oncology Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: Mural Oncology Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Mural Oncology Investigational Site
state: South Carolina
city: Houston
country: United States
facility: Mural Oncology Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: Mural Oncology Investigational Site
state: Utah
city: Milwaukee
country: United States
facility: Mural Oncology Investigational Site
state: Wisconsin
city: Edmonton
country: Canada
facility: Mural Oncology Investigational Site
state: Alberta
city: Hamilton
country: Canada
facility: Mural Oncology Investigational Site
state: Ontario
city: Montréal
country: Canada
facility: Mural Oncology Investigational Sites
state: Quebec
city: Montréal
country: Canada
facility: Mural Oncology Investigational Site
state: Quebec
city: Montréal
country: Canada
facility: Mural Oncology Investigational Site
state: Quebec
city: Québec
country: Canada
facility: Mural Oncology Investigational Site
state: Quebec
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Rotterdam
country: Netherlands
facility: Mural Oncology Investigational Site
city: Utrecht
country: Netherlands
facility: Mural Oncology Investigational Site
city: Badalona
country: Spain
facility: Mural Oncology Investigational Site
city: Córdoba
country: Spain
facility: Mural Oncology Investigational Site
city: Madrid
country: Spain
facility: Mural Oncology Investigational Site
city: Madrid
country: Spain
facility: Mural Oncology Investigational Site
city: Madrid
country: Spain
facility: Mural Oncology Investigational Site
city: Madrid
country: Spain
facility: Mural Oncology Investigational Site
city: Madrid
country: Spain
facility: Mural Oncology Investigational Site
city: Málaga
country: Spain
facility: Mural Oncology Investigational Site
city: Valencia
country: Spain
facility: Mural Oncology Investigational Site
city: Kaohsiung
country: Taiwan
facility: Mural Oncology Investigational Site
city: Taichung
country: Taiwan
facility: Mural Oncology Investigational Site
city: Tainan
country: Taiwan
facility: Mural Oncology Investigational Site
city: Taipei
country: Taiwan
facility: Mural Oncology Investigational Site
city: Taipei
country: Taiwan
facility: Mural Oncology Investigational Site
city: Taipei
country: Taiwan
facility: Mural Oncology Investigational Site
Study officials:
affiliation: Mural Oncology
name: Mural Oncology Medical Director
role: STUDY_DIRECTOR
References: