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

Phase 1

• Conditions: Advanced Solid Tumors; MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10027150 Term: Melanoma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001998-90-ES
• Lead Sponsor: Alkermes, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-06
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 293

Inclusion Criteria

1. The subject or the subject’s legal representative is willing and able to provide written informed consent.
2. The subject is aged =18 years.
3. For 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.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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.
9. Subjects must have adequate hematologic reserve as evidenced by:
• Absolute neutrophil count (ANC) of =1000/µL,
• Absolute lymphocyte count of =500/µL,
• Platelet count of =75,000/µL, and
• Hemoglobin of =9 g/dL (subjects may be transfused to this level if necessary).
10. Subjects must have adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values =3 × the upper limit of normal (ULN) (=5 × the ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of =1.5 × ULN (=2 × ULN for subjects with known Gilbert’s syndrome) for the reference laboratory.
11. Subjects must have adequate renal function as evidenced by a serum creatinine =1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of =60 mL/min by the Cockroft-Gault equation.
12. 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]).
13. 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

Exclusion Criteria

1. Subject is currently pregnant or breastfeeding or is planning to become pregnant during the study period
2. Subjects with an active infection or with a fever =38.5°C (=101.3°F) within 3 days of the first scheduled day of dosing
3. Subjects with active or symptomatic central nervous system metastases unless the metastases have been treated by surgery and/or radiation therapy, the subject has been tapered to a dose of 10 mg or less of corticosteroids for at least 2 weeks before the first dose, and the subject is neurologically stable
4. Subjects with known hypersensitivity to any components of ALKS 4230
5. Subjects who require pharmacologic doses of corticosteroids (greater than 10 mg of prednisone daily, or equivalent); however, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted. Use of glucocorticoids for the purpose of treating immune-mediated AEs is permitted (see Section 9.8) but may result in discontinuation from study based on consultation between the Investigator and the Medical Monitor. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
6. Subjects with mean QT interval corrected by the Fridericia Correction Formula values of >470 msec (in females) or >450 msec (in males) following 3 standard 12-lead electrocardiograms (ECGs) conducted approximately 5 minutes apart; subjects who are known to have congenital prolonged QT syndromes; or subjects who are on medications known to cause prolonged QT interval on ECG.
7. Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and neuropathy. (Subjects who have immune-mediated endocrinopathies and are stable on hormone replacement therapy are not excluded.) Subjects who developed other autoimmune disorders of Grade =3 may enroll if the disorder has resolved and the subject is off steroids for 2 weeks. Subjects who experienced autoimmune colitis as a toxicity of prior immunotherapy must undergo screening colonoscopy to rule out ongoing inflammation.
8. 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; other examples of such conditions would include unstable or poorly controlled hypertension; unstable angina; myocardial infarction, or cardiovascular accident within 6 months of study entry; New York Heart Association Grade 3 or 4 congestive heart failure; chronic obstructive pulmonary disease or diabetes mellitus that has required 2 or more hospitalizations in the last year; severe peripheral vascular disease; or recent serious trauma.
9. Subjects known to be positive for human immunodeficiency virus, hepatitis B or hepatitis C, or active tuberculosis or has a known history of tuberculosis.
10. Subjects who are employed by Alkermes, Syneos Health, the Investigator, the study center (included permanent or temporary contract workers and designees responsible for the conduct of the study), or other affiliate of this study or is immediate family of an employee of Alkermes, Syneos Health, the Investigator, the study center, or other biological or legal

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified