A Dose Escalation and Cohort Expansion Study of Subcutaneously-Administered Cytokine ALKS 4230 (Nemvaleukin Alfa) as a Single Agent and in Combination With Anti-PD-1 Antibody (Pembrolizumab) in Subjects With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)

Study Overview
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Brief Summary
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This study will characterize the safety and tolerability and identify the recommended Phase 2 dose (RP2D) of subcutaneous (SC) ALKS 4230 as monotherapy and in combination with pembrolizumab.

Detailed Description
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This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors.

Official Title
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A Phase 1/2 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-2 (001)

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: ALKS 4230
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Phase I the subject has histological or cytological evidence of a solid tumor. For Phase II the subject must have 1 of the specified adult solid tumor types: gastric, ovarian, lung, head and neck. Subject must have at least one target lesion based on RECIST Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 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 radiation therapy must wait at least 4 weeks after their last radiation treatment before enrollment into the study 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 Subject will agree to follow contraceptive requirements defined in the protocol Additional criteria may apply Exclusion Criteria: Subject is currently pregnant, planning to become pregnant, or breastfeeding Subjects with an active infection or with a fever ≥ 38.5°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 with known hypersensitivity to any components of ALKS 4230 or to pembrolizumab or any of its excipients Subjects who require pharmacologic doses of systemic corticosteroids are excluded; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and/or neuropathy Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subjects 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 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>Administered via SC injection once every 7 days or once every 21 days at escalating doses | Biological: ALKS 4230<br>* SC injection administered in the back of the arm or the abdomen<br>|
| Experimental: ALKS 4230 + pembrolizumab<br>ALKS 4230 will be administered via SC injection once every 7 or 21 days at escalating doses or at the recommended phase 2 dose and schedule; pembrolizumab will be administered as an intravenous infusion given over 30 minutes; the dose level for pembrolizumab will be 200 mg per the approved label. In December 2020, an RP2D of 3 mg with an administration schedule of q7d was determined for SC ALKS 4230. | Biological: ALKS 4230<br>* SC injection administered in the back of the arm or the abdomen<br>Biological: Pembrolizumab<br>* Administered as an intravenous (IV) infusion over 30 minutes<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A | Includes 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 | 
| Number of subjects experiencing AEs that are both serious and drug-related in Part B | Includes 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 | 
| Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type. | Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images | From time of therapy until the date of first documented tumor progression, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR) | Overall response rate (ORR) will be based on investigator review of radiographic or photographic images | 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 Partial Response (PR)/immune PR (iPR) | ORR will be based on investigator review of radiographic or photographic images | 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 | CR/iCR duration | Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | 
| Duration of response in subjects with PR/iPR | PR/iPR duration | Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | 
| Non-progression for Part B | Time from first dose of SC ALKS 4230 to the time of progression or death | Assessed up to 24 months | 
| Overall survival for Part B | Time from first dose of SC ALKS 4230 to the time of death | 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 (each cycle is 21 days), 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 (each cycle is 21 days), 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 (each cycle is 21 days), 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 until the last treatment cycle (each cycle is 21 days), assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian, Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine, ALKS 4230, Pembrolizumab, Keytruda, PD-L1, Solid tumors, Immunotherapy, nemvaleukin alfa, Head and Neck, NSCLC, Non small cell lung cancer, lung cancer, Gastric, Gastric Cancer, Gastroesophageal Cancer, Gastroesophageal junction (GEJ) adenocarcinoma, GEJ Cancer, adenocarcinoma