Clinical trial NCT02799095: A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on Subjects With Solid Tumors
Official title: A Phase 1/2 Study of ALKS 4230 Administered Intravenously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: Immunotherapy
IL-2
Interleukin-2
Solid tumors
Melanoma
Renal cell carcinoma
Non-small-cell lung cancer
Squamous cell carcinoma of the head and neck
in combination with pembrolizumab
Lead sponsor: Mural Oncology, Inc
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 243
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: To better understand the safety and tolerability of ALKS 4230 in humans

Detailed description: To investigate the safety and tolerability of ALKS 4230, determine the recommended Phase 2 dose (RP2D) and assess anti-tumor activity in Monotherapy and ALKS 4230 in Combination with pembrolizumab.

Eligibility criteria: Inclusion Criteria:

* For Part A, the subject has histological or cytological evidence of a solid tumor; for Part B, the subject has a diagnosis of melanoma or renal cell carcinoma
* All subjects must have advanced solid tumors that have returned after treatment with established approved therapies or be intolerant of established therapies
* Subjects enrolled in Part B or Part C must have at least 1 lesion that may qualify as a target lesion
* Subject can move around on their own, has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and has an estimated life expectancy of at least 3 months
* Subject must have adequate hematologic reserve
* 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 investigational agents must wait at least 4 weeks
* 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. A female not of childbearing potential is one who has undergone bilateral oophorectomies or who is postmenopausal, defined as \>45 years of age and without a menstrual period for 12 consecutive months
* Meets contraceptive requirements defined in the protocol
* Additional criteria may apply

Exclusion Criteria:

* Subject is currently pregnant or breastfeeding, or is planning to become pregnant during the study
* Subjects with an active infection or with a fever \>/= 38.5 degrees 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 have a mean QT interval corrected by the Fridericia Correction formula value of \>470 msec (in females) or \>450 msec (in males)
* Subjects with known hypersensitivity to any components of ALKS 4230
* Subjects with known hypersensitivity to any components of pembrolizumab (for patients in combination arm only)
* Subjects who require pharmacologic doses of corticosteroids; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted
* Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and neuropathy
* Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subject 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
* Subjects with dyspnea at rest of requiring oxygen therapy
* Subjects active autoimmune disease requiring systemic treatment within the past 30 days
* Subjects who received radiotherapy within the last 4 weeks before start of study treatment administration with the exception of limited field palliative radiotherapy
* Subjects who have received systemic immunomodulatory agents within 28 days prior to C1D1.
* Subjects who have received administration of a live, attenuated vaccine within 4 weeks of Cycle 1, Day1.
* Prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant recipients
* Subjects who have received prior IL-2 based or IL-15 based cytokine therapy
* Additional criteria may apply

Primary outcomes:
measure: Part A: Number of Participants With Dose-limiting Toxicities (DLTs) Based on Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 15 (Cycle 1 length = 14 days; Cycle 2 length= 21 days)
measure: Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
measure: Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
timeFrame: From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
measure: Parts B and C: Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
timeFrame: From first dose of study drug up to 40.3 months for Part B and up to 50.5 months for Part C
Secondary outcomes:
measure: Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
timeFrame: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dose
measure: Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
timeFrame: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dose
measure: Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
timeFrame: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dose
measure: Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
timeFrame: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dose
measure: Parts A, B, and C: Proportion of Positive Anti-Nemvaleukin Alfa Antibodies (ADA)
timeFrame: From first dose of study drug up to 9 months (for Part A); up to 40.3 months (for Part B); up to 50.5 months (for Part C)
measure: Parts A, B, and C: Immune ORR (iORR) Based on Immune RECIST (iRECIST)
timeFrame: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Parts A, B, and C: Disease Control Rate (DCR) Based on RECIST v.1.1
timeFrame: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Parts A, B, and C: Immune DCR (iDCR) Based on iRECIST v1.1
timeFrame: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Parts B, and C: Duration of Response (DOR) Based on RECIST v1.1
timeFrame: From the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause (up to 40.3 months for Part B and up to 50.5 months for Part C)
measure: Parts B, and C: Immune DOR (iDOR) Based on iRECIST
timeFrame: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Part B and Part C Cohorts C5, C6, C7: Durable Response Rate (DRR) Based on RECIST v.1.1
timeFrame: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Part B and Part C Cohorts C5, C6, C7: Immune DRR (iDRR) Based on iRECIST
timeFrame: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Part B and Part C Cohorts C5, C6, C7: Progression-free Survival (PFS) Based on RECIST v.1.1
timeFrame: From first dose of study drug up to the first documentation of objective tumor progression or death due to any cause (up to 40.3 months for Part B and up to 50.5 months for Part C)
measure: Part B and Part C Cohorts C5, C6, C7: Immune PFS (iPFS)
timeFrame: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part C
measure: Parts A, B and C: Maximum Cell Count of Whole Blood FoxP3+ T Cells (Tregs), Total Cluster of Differentiation (CD)8+ T Cells and Natural Killer (NK) Cells
timeFrame: Cycle 1 Day 1 (Cycle 1 length = 14 days for Part A and 21 days for Part B and C)
measure: Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
timeFrame: Cycle 1 Days 1 and 5; Cycle 2 Days 1 and 5 (Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Mural Oncology Investigational Site
state: Colorado
city: Port Saint Lucie
country: United States
facility: Mural Oncology Investigational Site
state: Florida
city: Tampa
country: United States
facility: Mural Oncology Investigational Site
state: Florida
city: Lexington
country: United States
facility: Mural Oncology Investigational Site
state: Kentucky
city: Boston
country: United States
facility: Mural Oncology Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Mural Oncology Investigational Site
state: Michigan
city: Buffalo
country: United States
facility: Mural Oncology Investigational Site
state: New York
city: New York
country: United States
facility: Mural Oncology Investigational Site
state: New York
city: Cleveland
country: United States
facility: Mural Oncology Investigational Site
state: Ohio
city: Dallas
country: United States
facility: Mural Oncology Investigational Site
state: Texas
city: Fairfax
country: United States
facility: Mural Oncology Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Mural Oncology Investigational Site
state: Washington
city: Albury
country: Australia
facility: Mural Oncology Investgational Site
state: New South Wales
city: Waratah
country: Australia
facility: Mural Oncology Investigational Site
state: New South Wales
city: Brussels
country: Belgium
facility: Mural Oncology Investigational Site
state: MO
city: Kortrijk
country: Belgium
facility: Mural Oncology Investigational Site
state: West-Vlaanderen
city: Edmonton
country: Canada
facility: Mural Oncology Investigational Site
state: Alberta
city: Hamilton
country: Canada
facility: Mural Oncology Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Alkermes Investigational Site
state: Ontario
city: Montréal
country: Canada
facility: Mural Oncology Investigational Site
state: Quebec
city: Québec
country: Canada
facility: Mural Oncology Investigational Site
state: Quebec
city: Daejeon
country: Korea, Republic of
facility: Mural Oncology Investigational Site
city: Seoul
country: Korea, Republic of
facility: Mural Oncology Investigational Site
city: Seoul
country: Korea, Republic of
facility: Mural Oncology Investigational Site
city: Skorzewo
country: Poland
facility: Mural Oncology Investigational Site
state: Poznan
city: Barcelona
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: Valencia
country: Spain
facility: Mural Oncology Investigational Site
Study officials:
affiliation: Mural Oncology
name: Medical Director
role: STUDY_DIRECTOR
References: