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)
- 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 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem 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)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002013-20-NL
- Lead Sponsor
- Alkermes, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 155
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 and progressive disease following at least one line of therapy.
4. For Phase 2, subject must have one of the following tumor types or specific histology:
• SCCHN cohort: subjects with regionally advanced and/or distantly metastatic head and neck squamous cell carcinoma of non-cutaneous origin that has relapsed or failed to achieve complete response after at least one line of systemic therapy given alone or in combination with surgery and /or radiation therapy.
• NSCLC cohort: subjects with locally advanced unresectable or metastatic NSCLC who have not been previously treated with immune checkpoint inhibitors (CPIs; anti-PD-1, anti-PD-L1, anti-CTLA-4) are eligible; patients who have progressed after other prior systemic therapy are allowed. Patients with EGFR, ALK, ROS1, or other known targetable genomic alterations must have received appropriate targeted treatment and progressed. Eligible patients will have PD-L1 tumor proportion score (TPS) less than 1% as determined by an approved test. If PD-L1 status is unknown during Screening, tumor tissue (fresh biopsy or archived samples) must be tested for PD-L1 expression prior to enrollment.
• Gastric/GEJ cohort: subjects with unresectable metastatic or locally advanced gastric or GEJ adenocarcinoma who have not been previously treated with immune CPIs (anti-PD-1, anti-PD-L1, anti-CTLA-4) and who have progressed on and/or after two prior regimens. Prior regimens had to have included a fluoropyrimidine and a platinum chemotherapy. Progression within 6 months of prior adjuvant or neoadjuvant chemotherapy will be deemed a rapid progressor and thus equivalent to one advanced/metastatic disease treatment regimen. Changing from IV to oral fluoropyrimidine without noted progression is considered only one prior regimen. Her2 positive patients must have received prior anti-Her2 therapy and demonstrate progressive disease. PD-L1 status must be known at the time of enrollment based on an approved test.
• Ovarian cancer cohort: subjects must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
5. Subject must have at least one target lesion based on RECIST.
6. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 and an estimated life expectancy of at least 3 months.
7. Subject has adequate hematologic reserves, measured within 7 days prior to start of study treatment as defined in the protocol
8. 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.
9. 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 Cockcroft-Gault equation measured within 10 days prior to start of study treatment.
10. Subject has recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, or surgery (ie, toxicity no wo
1. Subject is currently pregnant or breastfeeding or is planning to become pregnant during the study period.
2. Subjects who are investigational site staff members directly involved in the conduct of the trial and their immediate family members or subjects who are Alkermes or Syneos Health employees directly involved in the conduct of the study.
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 of Phase 1 or Cycle 1 of Phase 2.
4. Subjects who have received therapeutic systemic antibiotics within 14 days prior to starting investigational therapy excluded unless specifically exempted on a case-by-case basis by the Medical Monitor.
5. Subject has known hypersensitivity (Grade =3) to any components of ALKS 4230, to pembrolizumab, or any of its excipients.
6. 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.
7. Subject has developed Grade =3 autoimmune disorders while on prior immunotherapy, (e.g., 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 =2 may enroll if the disorder has resolved and the subject is off systemic steroids for =28 days. Subjects who experienced autoimmune colitis as a toxicity of prior immunotherapy must undergo colonoscopy to rule out ongoing inflammation. Vitiligo is not exclusionary
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.
8. Subjects who have received radiotherapy within the last 4 weeks before start of study treatment, with the exception of limited field palliative radiotherapy that has been completed at least 2 weeks before starting study treatment.
9. Subject has active or symptomatic central nervous system metastases unless the metastases have been treated by surgery and/or radiation therapy, and/or gamma knife, the subject has been tapered to a dose of 10 mg of prednisone (or equivalent) or less of corticosteroids for at least 2 weeks before the first dose of study agent(s), and the subject is neurologically stable. Patients with history of brain metastases or a suspicion of brain metastases must have a brain magnetic resonance imaging (MRI) at baseline.
10. Subject has an active autoimmune disease that has required systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that has required systemic steroids and/or immunosuppressive agents. Limited exceptions may be granted on a case-by-case basis by the Medical Monitor.
11. Subjects known to be positive for human immunodeficiency virus are excluded. Exceptions please see in the protocol.
12. Subjects with active tuberculosis or a known history of tuberculosis are excluded.
13. Subjects requiring pharmacologic doses of systemic corticosteroids (greater than 10 mg of prednisone daily, or equ
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