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

Sponsor

Alkermes, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02799095

Collaborator

(none)

243

Enrollment

Locations

Arms

Duration (Months)

7.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: ALKS 4230 Drug: ALKS 4230 + pembrolizumab	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

243 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2016

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 4230	Drug: ALKS 4230 Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period
Experimental: ALKS 4230 + pembrolizumab	Drug: 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

Arm

Intervention/Treatment

Experimental: ALKS 4230

Drug: ALKS 4230

Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period

Experimental: ALKS 4230 + pembrolizumab

Drug: 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

Outcome Measures

Primary Outcome Measures

Characterization of adverse events (AEs) and dose-limiting toxicities (DLT) in study Part A [From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months]
Incidence of AEs that are both serious and drug-related
Incidence of drug-related AEs in study Part B [From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months]
Incidence of AEs that are drug-related
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) [From time of initiation of therapy until 30 days after last dose of study drug assessed up to 24 months]
Proportion of patients with the confirmed overall response of complete response or partial response

Secondary Outcome Measures

Disease Control Rate [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 CR, PR, or Stable Disease (SD)
Duration of response in subjects with CR/iCR or PR/iPR [From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months]
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
Serum concentrations of ALKS 4230 will be determined at various time points [From time of initiation of therapy until the last treatment cycle, assessed up to 24 months]
Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level
Serum will be assayed for the presence of anti-ALKS 4230 antibodies [From time of initiation of therapy until the last treatment cycle, assessed up to 24 months]
Results will be summarized by dose level
Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points [From time of initiation of therapy until the last treatment cycle, assessed up to 24 months]
Results will be summarized by dose level
Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points [From time of initiation of therapy during the first two treatment cycles, assessed up to 2 months]
Results will be summarized by dose level

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Denver	Colorado	United States	80045
2	Alkermes Investigational Site	Port Saint Lucie	Florida	United States	34952
3	Alkermes Investigational Site	Tampa	Florida	United States	33610
4	Alkermes Investigational Site	Lexington	Kentucky	United States	40536
5	Alkermes Investigational Site	Boston	Massachusetts	United States	02215
6	Alkermes Investigational Site	Detroit	Michigan	United States	47201
7	Alkermes Investigational Site	Buffalo	New York	United States	14203
8	Alkermes Investigational Site	New York	New York	United States	10016
9	Alkermes Investigational Site	Cleveland	Ohio	United States	44106
10	Alkermes Investigational Site	Dallas	Texas	United States	75230
11	Alkermes Investigational Site	Fairfax	Virginia	United States	22031
12	Alkermes Investigational Site	Spokane	Washington	United States	99208
13	Alkermes Investgational Site	Albury	New South Wales	Australia	2640
14	Alkermes Investigational Site	Waratah	New South Wales	Australia	2298
15	Alkermes Investigational Site	Brussels	MO	Belgium	1200
16	Alkermes Investigational Site	Kortrijk	West-Vlaanderen	Belgium	8500
17	Alkermes Investigational Site	Edmonton	Alberta	Canada
18	Alkermes Investigational Site	Hamilton	Ontario	Canada
19	Alkermes Investigational Site	Toronto	Ontario	Canada
20	Alkermes Investigational Site	Montréal	Quebec	Canada
21	Alkermes Investigational Site	Québec	Quebec	Canada	G1R 2J6
22	Alkermes Investigational Site	Daejeon		Korea, Republic of	35015
23	Alkermes Investigational Site	Seoul		Korea, Republic of	02841
24	Alkermes Investigational Site	Seoul		Korea, Republic of	03722
25	Alkermes Investigational Site	Skorzewo	Poznan	Poland	60-185
26	Alkermes Investigational Site	Barcelona		Spain	8036
27	Alkermes Investigational Site	Madrid		Spain	28033
28	Alkermes Investigational Site	Madrid		Spain	28040
29	Alkermes Investigational Site	Madrid		Spain	28041
30	Alkermes Investigational Site	Madrid		Spain	28050
31	Alkermes Investigational Site	Valencia		Spain	46010