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 (001)
- Conditions
- Advanced solid tumors10027655
- Registration Number
- NL-OMON55159
- Lead Sponsor
- Alkermes, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
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,
and that has failed to achieve complete response or relapsed after (or subject
has become intolerant to) CPI (given alone or in combination with other
agents), and that is presently considered inoperable and unamenable to (re-)
irradiation.
• 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. 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. Patients with known MSI-high/dMMR status are not eligible.
• Ovarian cancer cohort: subjects must have recurrent high-grade serous,
endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal
cancer. Subject must have experienced a response lasting at least 3 months to
first-line platinum-based therapy but must be considered resistant to the last
administered platinum containing therapeutic regimen. Subjects must have
received prior monoclonal antibody that inhibits angiogenesis (e.g.,
bevacizumab) either as single agent or in combination or be deemed ineligible
or intolerant. Subject with a known BRCA-1 or -2 mutation must have received
prior poly ADP ribose polymerase (PARP) inhibitor. Subject must not have
received prior checkpoint inhibitor therapy.
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 evidenced by:
• Absolute neutrophil count 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).
8. Subject has adequate hepatic function as evidenced by aspartate transaminase
and alanine aminotransferase values <=3 × the upper limit of norm
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, site staff members
otherwise supervised by the Investigator, or subjects who are Alkermes or
Syneos Health employees directly involved in the conduct of the study
(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 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. Antibiotics given for
peri-procedural prophylaxis or given presumptively for a limited time (e.g.,
until infection was ruled out), as well as topical or intra-ocular antibiotics,
shall not be exclusionary.
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.
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. Replacement therapy (eg, thyroxine, insulin, or physiologic
corticosteroid replacement therapy
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br><br /><br>• The incidence and severity of treatment-emergent adverse events (AEs) (Phase<br /><br>1 and Phase 2)<br /><br>• ORR based on RECIST 1.1 (Phase 2)</p><br>
- Secondary Outcome Measures
Name Time Method