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

Study Overview
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Brief Summary
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To better understand the safety and tolerability of ALKS 4230 in humans

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: ALKS 4230
* Drug: ALKS 4230 + pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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