A Phase 1/2 Study of ALKS 4230 Administered Subcutaneouslyas Monotherapy and in Combination With Pembrolizumab inSubjects With Advanced Solid Tumors(ARTISTRY-2)
- Conditions
- Advanced Solid TumorsMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10041823Term: Squamous cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002013-20-DE
- Lead Sponsor
- Alkermes, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 257
1. Subject is aged =18 years.
2. Subject or the subject’s legal representative provides written informed consent.
3. For Phase 1, Subject must have an advanced solid tumor (including lymphoma) and progressive disease following at least 1 line of therapy.
4. For Phase 2, subject must have one of the following tumor types or specific histology:
• NSCLC cohort: Subjects with Stage IIIB or IV NSCLC who have been treated with checkpoint inhibitors with stable disease or better and followed by progression more than 120 days after initiation of the checkpoint inhibitor therapy.
• SCCHN cohort: Subjects with recurrent or metastatic SCCHN with disease progression on or after chemotherapy and who have not received prior checkpoint inhibitor therapy.
• Squamous tumor agnostic cohort: Subjects with recurrent or metastatic squamous cell carcinoma following chemotherapy and who have not received prior checkpoint inhibitor therapy. Patients with SCCHN should enroll in the SCCHN cohort if they meet those eligibility criteria.
• HCC cohort: Subjects with recurrent or metastatic HCC with disease progression on or after antitumor therapy who have not received prior checkpoint inhibitor therapy.
• SCLC cohort: Subjects with unresectable or metastatic SCLC who have progressed on or after a minimum of 4 cycles of chemotherapy which may have included maintenance checkpoint inhibitor therapy. Subjects who have received prior checkpoint inhibitor therapy and had stable disease or better and who subsequently progressed are eligible provided that the progression was more than 120 days of the initiation of checkpoint inhibitor therapy.
5. Subject must have measurable disease based on RECIST.
6. Subject must have completed the last dose of any broad spectrum antibiotic at least 30 days prior to first dose.
7. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
8. Subject has adequate hematologic reserves, measured within 10 days prior to start of study treatment, as evidenced by:
• Absolute neutrophil count of =1000/µL without growth factor support in prior month,
• Absolute lymphocyte count of =500/µL,
• Platelet count of =75,000/µL without platelet transfusion support in prior month, and
• Hemoglobin of =9 g/dL (subjects may be transfused to this level if necessary).
9. Subject has adequate hepatic function as evidenced by aspartate transaminase and alanine aminotransferase values =3 × the upper limit of normal (ULN) (=5 × 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 measured within 10 days prior to start of study treatment.
10. Subject has adequate renal function as evidenced by a serum creatinine =1.5 × ULN for the reference laboratory or a calculated creatinine clearance of =45 mL/min by the Cockroft-Gault equation measured within 10 days prior to start of study treatment.
11. Subject has recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, or surgery (ie, toxicity no worse than Grade 1 [any grade alopecia and treatment-associated peripheral neuropathy are acceptable]).
12. Subject who has received standard or 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
1. Subject is currently pregnant or breastfeeding or is planning to become pregnant during the study period.
2. Subject is employed by Alkermes, Syneos Health, the Investigator, the study center (including permanent or temporary contact 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 affiliate. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
3. Subject has an active infection or a fever =38.5°C (=101°F) within 3 days of the first scheduled day of dosing for the monotherapy lead-in or Cycle 1 of Phase 2.
4. Subject has known hypersensitivity (Grade =3) to any components of ALKS 4230, to pembrolizumab, or any of its excipients.
5. Subjects with mean QT interval corrected by the Fridericia Correction Formula values of >470 msec (in females) or >450 msec (in males) following a standard 12-lead electrocardiogram (ECG); subjects who are known to have congenital prolonged QT syndromes; or subjects who are on medications known to cause prolonged QT interval on ECG.
6. Subject has developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and neuropathy. Subject was discontinued from prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, or CD137) due to a Grade 3 or higher immune-related AE.
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 or must have been evaluated by colonoscopy to rule out ongoing inflammation.
7. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
8. Subject has active or symptomatic central nervous system metastases unless the metastases have been treated by surgery and/or radiation therapy, the subject has been dose, and the subject is neurologically stable.
9. Subject has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
10. Subject is known to be positive for human immunodeficiency virus and/or history of hepatitis B, or C infections or is known to be positive for hepatitis B antigen (HBsAg)/hepatitis B virus (HBV) DNA or hepatitis C antibody (Hep C Ab) or RNA.
11. Subject requires 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method