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

• ClinicalTrials.gov Identifier: NCT02799095
• Recruitment Status: Active, not recruiting
• First Posted: June 14, 2016
• Last Update Posted: November 25, 2022
• Sponsor: Alkermes, Inc.
• Information provided by (Responsible Party): Alkermes, Inc.

Tracking Information

• First Submitted Date: June 1, 2016
• First Posted Date: June 14, 2016
• Last Update Posted Date: November 25, 2022
• Study Start Date: July 2016
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

• Characterization of adverse events (AEs) and dose-limiting toxicities (DLT) in study Part A [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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

Original Primary Outcome Measures (submitted: June 9, 2016)

• Characterization of adverse events (AEs) and dose-limiting toxicities (DLT) in study Part A [ Time Frame: From date of randomization until the date of first documented tumor progression, assessed up to 24 months ]
  Incidence of AEs that are both serious and drug-related
• Incidence of drug-related AEs in study Part B [ Time Frame: From date of randomization until the date of first documented tumor progression, assessed up to 24 months ]

Current Secondary Outcome Measures (submitted: May 7, 2020)

• Disease Control Rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From time of initiation of therapy during the first two treatment cycles, assessed up to 2 months ]
  Results will be summarized by dose level

Original Secondary Outcome Measures (submitted: June 9, 2016)

• Overall response rate (ORR) based on investigator review of radiographic or photographic images [ Time Frame: From date of randomization until the date of first documented tumor progression, assessed up to 24 months ]
  Proportion of subjects with objective evidence of Complete Response (CR/irCR) or Partial Response (PR/irPR)
• Disease Control Rate [ Time Frame: From date of randomization 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 or PR [ Time Frame: From date of randomization until the date of first documented tumor progression, assessed up to 24 months ]
  Time from the first documentation of response (CR or PR) 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 [ Time Frame: From date of randomization until the date of first documented tumor progression, 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 [ Time Frame: From date of randomization until the date of first documented tumor progression, 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 [ Time Frame: From date of randomization until the date of first documented tumor progression, 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 [ Time Frame: From date of randomization until the date of first documented tumor progression, assessed up to 24 months ]
  Results will be summarized by dose level

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on Subjects With Solid Tumors
• 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
• Brief Summary: To better understand the safety and tolerability of ALKS 4230 in humans
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors

Intervention

• Drug: ALKS 4230
  Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period
• 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

Study Arms

• Experimental: ALKS 4230
  Intervention: Drug: ALKS 4230
• Experimental: ALKS 4230 + pembrolizumab
  Intervention: Drug: ALKS 4230 + pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 27, 2021): 243
• Original Estimated Enrollment (submitted: June 9, 2016): 120
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Korea, Republic of, Poland, Spain, United States

Administrative Information

• NCT Number: NCT02799095
• Other Study ID Numbers: ALK4230-A101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: At this time, IPD sharing has not been defined and/or decided if it will be shared.

• Current Responsible Party: Alkermes, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alkermes, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Alkermes, Inc.

• PRS Account: Alkermes, Inc.
• Verification Date: November 2022