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)
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| ClinicalTrials.gov Identifier: NCT03861793 |
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Recruitment Status :
Active, not recruiting
First Posted : March 4, 2019
Last Update Posted : February 2, 2023
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Sponsor:
Alkermes, Inc.
Information provided by (Responsible Party):
Alkermes, Inc.
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Solid Tumors | Biological: ALKS 4230 Biological: Pembrolizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 185 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | February 26, 2019 |
| Estimated Primary Completion Date : | February 2023 |
| Estimated Study Completion Date : | December 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: ALKS 4230
Administered via SC injection once every 7 days or once every 21 days at escalating doses
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Biological: ALKS 4230
SC injection administered in the back of the arm or the abdomen |
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Experimental: ALKS 4230 + pembrolizumab
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.
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Biological: ALKS 4230
SC injection administered in the back of the arm or the abdomen Biological: Pembrolizumab Administered as an intravenous (IV) infusion over 30 minutes
Other Name: Keytruda |
Primary Outcome Measures :
- 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 ]Includes AEs that are both serious and drug-related
- Number of subjects experiencing AEs that are both serious and drug-related in Part B [ Time Frame: From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months ]Includes AEs that are both serious and drug-related
- Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type. [ Time Frame: From time of therapy until the date of first documented tumor progression, assessed up to 24 months ]Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images
Secondary Outcome Measures :
- 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 ]Overall response rate (ORR) will be based on investigator review of radiographic or photographic images
- 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 ]ORR will be based on investigator review of radiographic or photographic images
- 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) ]CR/iCR duration
- 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) ]PR/iPR duration
- Non-progression for Part B [ Time Frame: Assessed up to 24 months ]Time from first dose of SC ALKS 4230 to the time of progression or death
- Overall survival for Part B [ Time Frame: Assessed up to 24 months ]Time from first dose of SC ALKS 4230 to the time of death
- 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 ]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 (each cycle is 21 days), 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 (each cycle is 21 days), 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 until the last treatment cycle (each cycle is 21 days), assessed up to 24 months ]Results will be summarized by dose level
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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: 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03861793
Locations
Show 48 study locations
Sponsors and Collaborators
Alkermes, Inc.
Investigators
| Study Director: | Alkermes Medical Director | Alkermes, Inc. |
| Responsible Party: | Alkermes, Inc. |
| ClinicalTrials.gov Identifier: | NCT03861793 |
| Other Study ID Numbers: |
ALKS 4230-001 |
| First Posted: | March 4, 2019 Key Record Dates |
| Last Update Posted: | February 2, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Alkermes, Inc.:
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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 |
Additional relevant MeSH terms:
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Neoplasms Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents |