A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on Subjects With Solid Tumors

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02799095
• Other study ID #: ALK4230-A101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2016
• Est. completion date: August 2, 2023

Study information

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

Clinical Trial Summary

To better understand the safety and tolerability of ALKS 4230 in humans

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: August 2, 2023
• Est. primary completion date: August 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• ALKS 4230
Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period
• ALKS 4230 + pembrolizumab
IV infusion of ALKS 4230 over 30 minutes given daily for 5 consecutive days followed by an off-treatment period; pembrolizumab administered IV once with ALKS 4230 on the first day of each cycle

Locations

Country	Name	City	State
Australia	Mural Oncology Investgational Site	Albury	New South Wales
Australia	Mural Oncology Investigational Site	Waratah	New South Wales
Belgium	Mural Oncology Investigational Site	Brussels	MO
Belgium	Mural Oncology Investigational Site	Kortrijk	West-Vlaanderen
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	Québec	Quebec
Canada	Alkermes Investigational Site	Toronto	Ontario
Korea, Republic of	Mural Oncology Investigational Site	Daejeon
Korea, Republic of	Mural Oncology Investigational Site	Seoul
Korea, Republic of	Mural Oncology Investigational Site	Seoul
Poland	Mural Oncology Investigational Site	Skorzewo	Poznan
Spain	Mural Oncology Investigational Site	Barcelona
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	Valencia
United States	Mural Oncology Investigational Site	Boston	Massachusetts
United States	Mural Oncology Investigational Site	Buffalo	New York
United States	Mural Oncology Investigational Site	Cleveland	Ohio
United States	Mural Oncology Investigational Site	Dallas	Texas
United States	Mural Oncology Investigational Site	Denver	Colorado
United States	Mural Oncology Investigational Site	Detroit	Michigan
United States	Mural Oncology Investigational Site	Fairfax	Virginia
United States	Mural Oncology Investigational Site	Lexington	Kentucky
United States	Mural Oncology Investigational Site	New York	New York
United States	Mural Oncology Investigational Site	Port Saint Lucie	Florida
United States	Mural Oncology Investigational Site	Spokane	Washington
United States	Mural Oncology Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mural Oncology, Inc

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterization of adverse events (AEs) and dose-limiting toxicities (DLT) in study Part A	Incidence of 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	Incidence of drug-related AEs in study Part B	Incidence of AEs that are drug-related	From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months
Primary	Overall response rate (ORR) of ALKS 4230 monotherapy in patients with melanoma or renal cell carcinoma (Part B) and in combination with pembrolizumab in patients with advanced solid tumors (Part C)	Proportion of patients with the confirmed overall response of complete response or partial response	From time of initiation of therapy until 30 days after last dose of study drug assessed up to 24 months
Secondary	Disease Control Rate	Proportion of subjects with objective evidence of CR, PR, or Stable Disease (SD)	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 or PR/iPR	Time from the first documentation of response (CR/iCR or PR/iPR) to the first documentation of objective tumor progression or death due to any cause	From time of initiation of therapy until the date of first documented tumor progression, 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, 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, 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, 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 during the first two treatment cycles, assessed up to 2 months