Details

Details

Title A Phase 1 Study of ALKS 4230 in Subjects with Advanced Solid Tumors

IRB ALK1Y16

CC 16-804

Hospital Main Campus

Phase Phase 1

Disease Solid Tumors

Drug ALKS 4230

Description

Description

Dose Escalation - Part A

Primary Objective

  • To investigate the safety and tolerability of ALKS 4230 and to determine the MTD and the RP2D of ALKS 4230 in subjects with advanced solid tumors who are refractory or intolerant to therapies known to provide clinical benefit.
Secondary Objectives
  • To describe the dose-limiting toxicity (DLT) of ALKS 4230
  • To describe the adverse event (AE) profile of ALKS 4230
  • To characterize the clinical PK profile and immunogenicity of ALKS 4230
  • To investigate the clinical pharmacodynamic effects of ALKS 4230
  • To describe any antitumor activity and responses observed with ALKS 4230.

Dose Expansion - Part B

Primary Objective

  • To further characterize the safety profile of the ALKS 4230 at the RP2D in subjects with specified tumor types who have previously received specified prior therapies known to provide clinical benefit.
Secondary Objectives
  • To describe the AE profile of ALKS 4230
  • To characterize the clinical PK profile and immunogenicity of ALKS 4230
  • To investigate the clinical pharmacodynamics effects of ALKS 4230
  • To evaluate the overall response rate (ORR) and duration of response (DOR) for subjects treated with ALKS 4230 in each of the expansion cohorts.

Inclusion Criteria

Inclusion Criteria

  1. The subject or the subject's legal representative is willing and able to provide written informed consent.
  2. The subject is ≥18 years of age.
  3. For the dose-escalation portion of the study, the subject has histological or cytological evidence of a solid tumor; for the dose-expansion portion of the study, the subject has histological or cytological evidence of 1 of the following solid tumor types: melanoma, renal cell carcinoma, or ovarian cancer.
  4. All subjects must have advanced solid malignancies that are refractory to established therapies known to provide clinical benefit for the malignancy in question, or be intolerant of established therapies known to provide clinical benefit for the malignancy in question. Treatment with prior immunotherapy is permitted, with the exception of 1 cohort of subjects with renal cell carcinoma who are not permitted to have received prior treatment with an immune checkpoint inhibitor.
  5. Subjects enrolled in the dose-expansion portion of the study must have at least 1 lesion that may qualify as a target lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  6. 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.
  7. Subjects must have adequate hematologic reserve as evidenced by:
    • Absolute neutrophil count of ≥1,000/μL,
    • Absolute lymphocyte count of ≥500/μL,
    • Platelet count of ≥75,000/μL, and
    • Hemoglobin of ≥9 gm/dL (subjects may be transfused to this level if necessary).
  8. Subjects must have adequate hepatic function as evidenced by aspartate transaminase (AST) and alanine transaminase (ALT) values ≤3 x the upper limit of normal (ULN) (≤5 x the ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of ≤1.5 the ULN (≤2 x ULN for subjects with known Gilbert's syndrome) for the reference laboratory.
  9. Subjects must have adequate renal function as evidenced by a serum creatinine ≤1.5 x the ULN for the reference laboratory or a calculated creatinine clearance of ≥60 mL/min by the Cockroft-Gault equation.
  10. Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy or surgery (ie, toxicity no worse than Grade 1); for subjects who have been on monoclonal antibody therapy, at least 5 half-lives or 4 weeks (whichever is shorter) should have elapsed before the first scheduled day of dosing with ALKS 4230.
  11. Subjects who have received investigational agents must wait at least 5 half-lives or 4 weeks (whichever is shorter) before enrollment into the study, or 4 weeks if the half-life of the investigational agent is not known.
  12. Females of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment, and also 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.
  13. Meets contraceptive requirements defined in the protocol in Section 7.4.2.
Exclusion Criteria

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 within 3 days of the first scheduled day of dosing for Cycle 1.
  3. 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.
  4. Subjects with known hypersensitivity to any components of ALKS 4230.
  5. Subjects who require pharmacologic doses of corticosteroids; replacement doses, topical, ophthalmologic, and inhalational steroids are 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 5 minutes apart from each other; 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 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. The subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B, or C.
  10. Is employed by Alkermes, INC Research, the investigator, the study center (included permanent or temporary contract workers and designees responsible for the conduct of the study), or a third-party agent of this study or is immediate family of an employee of Alkermes, INC Research, the investigator, the study center, or third-party agent. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.