Description:
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.
Title
- Brief Title: 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)
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
ALKS 4230-001
- NCT ID:
NCT03861793
Conditions
Interventions
Drug | Synonyms | Arms |
---|
ALKS 4230 | | ALKS 4230 |
Pembrolizumab | Keytruda | ALKS 4230 + pembrolizumab |
Purpose
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
This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination
with pembrolizumab in subjects with advanced solid tumors.
Trial Arms
Name | Type | Description | Interventions |
---|
ALKS 4230 | Experimental | Administered via SC injection once every 7 days or once every 21 days at escalating doses | |
ALKS 4230 + pembrolizumab | Experimental | 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. | |
Eligibility Criteria
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 defined in
the protocol
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A |
Time Frame: | From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months |
Safety Issue: | |
Description: | Includes AEs that are both serious and drug-related |
Secondary Outcome Measures
Measure: | Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR) |
Time Frame: | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months |
Safety Issue: | |
Description: | Overall response rate (ORR) will be based on investigator review of radiographic or photographic images |
Measure: | Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR) |
Time Frame: | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months |
Safety Issue: | |
Description: | ORR will be based on investigator review of radiographic or photographic images |
Measure: | Duration of response in subjects with CR/iCR |
Time Frame: | 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) |
Safety Issue: | |
Description: | CR/iCR duration |
Measure: | Duration of response in subjects with PR/iPR |
Time Frame: | 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) |
Safety Issue: | |
Description: | PR/iPR duration |
Measure: | Non-progression for Part B |
Time Frame: | Assessed up to 24 months |
Safety Issue: | |
Description: | Time from first dose of SC ALKS 4230 to the time of progression or death |
Measure: | Overall survival for Part B |
Time Frame: | Assessed up to 24 months |
Safety Issue: | |
Description: | Time from first dose of SC ALKS 4230 to the time of death |
Measure: | 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 (each cycle is 21 days), assessed up to 24 months |
Safety Issue: | |
Description: | Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level |
Measure: | 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 (each cycle is 21 days), assessed up to 24 months |
Safety Issue: | |
Description: | Results will be summarized by dose level |
Measure: | 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 (each cycle is 21 days), assessed up to 24 months |
Safety Issue: | |
Description: | Results will be summarized by dose level |
Measure: | Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points |
Time Frame: | From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months |
Safety Issue: | |
Description: | Results will be summarized by dose level |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Alkermes, Inc. |
Trial Keywords
- Alkermes
- IL-2
- Interleukin-2
- Oncology
- Immuno-oncology
- Cytokine
- ALKS 4230
- Pembrolizumab
- Keytruda
- PD-L1
- Solid tumors
- Immunotherapy
- nemvaleukin alfa
- ovarian
- Head and Neck
- NSCLC
- Non small cell lung cancer
- lung cancer
- Gastric
- Gastric Cancer
- Gastroesophageal Cancer
- Gastroesophageal junction (GEJ) adenocarcinoma
- GEJ Cancer
- adenocarcinoma
Last Updated
May 28, 2021