Brief Summary

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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

243

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Sep 2016

Longer than P75 for phase_1

Geographic Reach

7 countries

31 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.9 years study duration

First Submitted

Initial submission to the registry

June 1, 2016

Completed

13 days until next milestone

First Posted

Study publicly available on registry

June 14, 2016

Completed

3 months until next milestone

Study Start

First participant enrolled

September 14, 2016

Completed

6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 27, 2023

Completed

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 2, 2023

Completed

1.8 years until next milestone

Results Posted

Study results publicly available

May 21, 2025

Completed

Last Updated

May 21, 2025

Status Verified

May 1, 2025

Enrollment Period

6.5 years

First QC Date

June 1, 2016

Results QC Date

March 21, 2025

Last Update Submit

May 2, 2025

Conditions

Advanced Solid Tumors

Keywords

ImmunotherapyIL-2Interleukin-2Solid tumorsMelanomaRenal cell carcinomaNon-small-cell lung cancerSquamous cell carcinoma of the head and neckin combination with pembrolizumab

Outcome Measures

Primary Outcomes (4)

Part A: Number of Participants With Dose-limiting Toxicities (DLTs) Based on Common Terminology Criteria for Adverse Events (CTCAE)
DLT was defined by any of following events possibly, probably, or definitely related to ALKS 4230: Grade 4 neutrophil count decreased (neutropenia); Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; Thrombocytopenia; Any Grade 3 cardiac or central nervous system toxicity; Liver transaminase elevation higher than 8\*upper limit of normal (ULN) or total bilirubin higher than 6\*ULN; Grade 4 hypoalbuminemia; Fever more than (\>) 40 degree Celsius (°C) sustained for \>24 hours; Hypotension required the use of pressors or prolonged hospitalization (\>48 hours) for hypotension requiring medical intervention; Grade 3 or higher electrolyte abnormalities; Increase in amylase or lipase; Grade 3 or higher nausea, vomiting, or diarrhea; Any other Grade 4 nonhematologic toxicity or any other Grade 3 non-hematologic toxicity; Any other toxicity or adverse event (AE) not defined above that resulted in participant removal from the study or discontinuation of dosing by the Investigator.
Cycle 1 Day 1 through Cycle 2 Day 15 (Cycle 1 length = 14 days; Cycle 2 length= 21 days)
Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product.
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)
Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. Severity was graded according to the National Cancer Institute (NCI) CTCAE (version 4.03) where, Grade 1: Mild- asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate- minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. As planned, Grades 1 and 2 were combined for reporting.
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)
Parts B and C: Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
ORR rate was defined as the percentage of participants with objective evidence of CR or PR based on RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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 (16)

Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
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
Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
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
Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
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
Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
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
Parts A, B, and C: Proportion of Positive Anti-Nemvaleukin Alfa Antibodies (ADA)
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)
+11 more secondary outcomes

Study Arms (2)

ALKS 4230

EXPERIMENTAL

Drug: ALKS 4230

ALKS 4230 + pembrolizumab

EXPERIMENTAL

Drug: ALKS 4230 + pembrolizumab

Interventions

ALKS 4230DRUG

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

ALKS 4230

ALKS 4230 + pembrolizumabDRUG

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

ALKS 4230 + pembrolizumab

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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.
+3 more criteria

Contact the study team to confirm eligibility.