A Phase I/II Study of ALKS 4230 Administered Intravenously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-1.

Study Identifier:
ALK4230-A101
CT.gov Identifier:
NCT02799095
EudraCT Identifier:
2019-001998-90
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To evaluate the safety, tolerability and immunological pharmacodynamic effects of ALKS 4230 in the treatment of patients with advanced solid tumors.

Dose-escalation stage: To determine a maximum tolerated dose, and to identify the optimal dose range of ALKS 4230 based on measures of immunological-pharmacodynamic effects.

To determine a recommended phase 2 dose and

To characterize the safety profile, pharmacokinetics (PK), pharmacodynamics (PD) and evidence of antitumor activity.

To evaluate the safety and anti-tumor activity of ALKS 4230 in combination with pembrolizumab will be assessed in certain PD-1 approved tumor types in both refractory and treatment naive patients, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, gastric cancer, urothelial carcinoma and microsatellite instability-high cancers.

To assess the combination in certain PD-1 unapproved tumor types, including colorectal cancer, triple-negative breast cancer, ovarian carcinoma, soft tissue sarcomas, and patients with metastatic NSCLC whose tumors express low or undetectable PD-L1 (tumor proportion score <1%).

Other assessments include pharmacokinetics, lymphocyte subpopulation expansion, immunogenicity, and anti-tumor activity.

To investigate the ALKS 4230 as monotherapy and in combination with pembrolizumab in adults with advanced solid tumors.

Outcomes include the monotherapy recommended phase 2 dose (RP2D), safety, pharmacodynamics, and antitumor activity

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.

To Report extended follow-up from combination therapy and new ALKS 4230 monotherapy data.

Outcomes presented include safety, PK/pharmacodynamics, RP2D, and antitumor activity (RECIST v1.1 & iRECIST) from Parts B & C

Outcomes presented include antitumor activity (RECIST v1.1) and safety as of 7/24/2020. To evaluate changes in tumor microenvironment (TME), baseline and on-treatment biopsies were collected.

To study IV nemvaleukin alone and in combination with pembrolizumab in pts with advanced solid tumors.

Investigator-assessed antitumor activity (confirmed responses as per RECIST v1.1) and safety are reported.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Study will be conducted in two stages:
    • Read More
  • Drug: Arms:
  • Drug: Experimental: ALKS 4230 + pembrolizumab
  • Drug: The study has three distinct stages: the ongoing monotherapy dose-escalation stage, the planned monotherapy dose-expansion stage and the newly initiated combination therapy stage with pembrolizumab. Upon completion of the dose-escalation stage, the initiation of monotherapy dose-expansion stage in up to 42 patients with renal cell carcinoma or melanoma is planned. The combination therapy stage will be run independent of, and concurrently with, the monotherapy dose-escalation and dose-expansion stages of the trial. Anti-tumor response and duration of response assessments in the dose-expansion and combination stages of the phase 1 study will be based on investigator-assessed, immune-related response (irRC) criteria and independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.
  • Drug: ASCO 2017
  • Drug: ALKS 4230 is administered as a 30 minute intravenous infusion once daily for 5 consecutive days repeating in treatment cycles of 14 days (first cycle) or 21 days (subsequent cycles).
  • Drug: Patients received a dosage range of 0.1 µg/kg/day to 6 µg/kg/day.
  • Drug: For monotherapy dose escalation, ALKS 4230 is administered intravenously over 30 minutes once daily for 5 days every 14 or 21 days. For combination therapy, the same regimen of ALKS 4230 is administered with pembrolizumab every 21 days in cohorts based on tumor type, prior anti-PD-1 therapy, and rollover from monotherapy.
  • Drug: ESMO 2020:
  • Drug: SITC 2020:
  • Drug: ASCO 2021:
  • Drug: ASCO GU 2022:
  • Drug: ASCO GI 2022:
  • Drug: ASCO 2022
  • Drug: ESGO 2022:
  • Drug: As per Pubmed:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    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
    • EUCTR:
    • The subject or the subject’s legal representative is willing and able to provide written informed consent.
    • The subject is aged > or = 18 years.
    • 3For the dose-escalation portion of the study, the subject has a diagnosis of an advanced solid tumor; for the dose-expansion portion of the study (Part B), the subject has a diagnosis of melanoma or RCC.
    • All subjects must have an advanced solid tumor (including lymphomas) that is refractory or, in the judgment of their physician, intolerant to established therapies known to provide clinical benefit for the malignancy in question. Treatment with prior immunotherapy is permitted, with the exception of subjects enrolling in the PD-1/L1 approved tumor types (PD-1/L1 treatment naive) cohort in Part C who are not permitted to have received prior treatment with an anti-PD-1/L1 therapy or prior IL-2 or IL-15 cytokine therapy.
    • Subjects enrolled in the dose-expansion monotherapy part (Part B) or combination therapy part (Part C) of the study must have at least 1 lesion that qualifies as a target lesion based on RECIST.
    • Subjects enrolled in the dose-expansion monotherapy part (Part B) or combination therapy part (Part C) of the study must specifically indicate on the informed consent that he or she agrees to provide archival tumor tissue biopsy sample(s). The archival tumor tissue sample does not have to be obtained prior to enrollment into the study, however every effort should be made to obtained before the subject completes study participation.
    • Subjects enrolled in the combination therapy part (Part C) of the study must have completed the last dose of any broad spectrum antibiotic at least 30 days prior to first dose (Cycle 1, Day 1).
    • Subject is ambulatory with an Eastern Cooperative Oncology Group (ECOG)
    • performance status of 0 or 1 and an estimated life expectancy of at least 3 months.
    • Subjects must have adequate hematologic reserve as evidenced by:
    • Absolute neutrophil count (ANC) of > or = 1000/µL,
    • Absolute lymphocyte count of > or = 500/µL,
    • Platelet count of > or = 75,000/µL, and
    • Hemoglobin of > or = 9 g/dL (subjects may be transfused to this level if necessary).
    • Subjects must have adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values < or = 3 × the upper limit of normal (ULN) (< or = 5 × the ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of < or = 1.5 × ULN (< or = 2 × ULN for subjects with known Gilbert’s syndrome) for the reference laboratory.
    • Subjects must have adequate renal function as evidenced by a serum creatinine < or = 1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of > or = 60 mL/min by the Cockroft-Gault equation.
    • Subjects must be recovered from the effects of any previous chemotherapy,
    • immunotherapy, other prior systemic anticancer therapy, radiotherapy, or surgery (ie, toxicity no worse than Grade 1 [Grade 2 alopecia and treatment-associated peripheral neuropathy are acceptable]).
    • Subjects who have received standard or investigational agents must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study, or 4 weeks if the half-life of the investigational agent is not known.
    • Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment, and on Day 1 before the first dose is administered. A woman is considered as a WOCBP (fertile) following menarche and until becoming postmenopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
    • Meets contraceptive requirements defined in protocol Section 8.4.2. Women of childbearing potential and men (if their sexual partners are WOCBP) must use at least 1 highly effective form of birth control throughout the study. Highly effective methods of birth control include true sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk, in line with the preferred and usual lifestyle of the patient), surgery (bilateral tubal ligation or occlusion, vasectomized partner), progestogen-only or estrogen/progestogen hormonal contraceptive associated with inhibition of ovulation (oral, patch, injectable, implantable, or intravaginal), intrauterine device, or intrauterine hormone-releasing system. See Section 8.4.2 for a definition of WOCBP and a complete description of contraceptive requirements.
    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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Solid Tumor