Advanced solid tumors Advanced solid tumors
Conditions
Interventions
ALKS 4230 drug product is supplied in three concentrations: 1 mg/mL, 5 mg/mL,
and 15 mg/mL. Each concentration is supplied as a single-dose vial.
Reconstituted ALKS 4230 is administered by SC injecti
Sponsors
Alkermes, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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 =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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints: • The incidence and severity of treatment-emergent adverse events (AEs) (Phase 1 and Phase 2) • ORR based on RECIST 1.1 (Phase 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: -The incidence of DLTs from the beginning of first dose of investigational agent(s) through the end of the DLT observation period (Phase 1) -Serum concentrations of ALKS 4230 and descriptive PK parameters (Phase 1 and Phase 2) -Presence of anti-ALKS 4230 antibodies in serum (Phase 1 and Phase 2) -Numbers of circulating cluster of differentiation (CD)8+ T cells, T regulatory cells (Tregs), and natural killer cells in peripheral blood (Phase 1 and Phase 2) -Serum concentrations of interleukin-6 and other cytokines (Phase 1 and Phase 2) -ORR, Disease Control Rate (DCR), Duration of Response (DOR), Time to Response (TTR), and Progression Free Survival (PFS) per RECIST 1.1 (Phase 1) -Immune ORR (iORR), immune DCR (iDCR), immune DOR (iDOR), immune TTR (iTTR), and immune PFS (iPFS) per immune RECIST (iRECIST) (Phase 1) -DCR, DOR, TTR, and PFS, per RECIST 1.1 (Phase 2) -iORR, iDCR, iDOR, iTTR, and iPFS, per iRECIST (Phase 2) -Overall survival (OS) (Phase 2) Exploratory endpoints may include the following: • Density of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) • Ratio of cytotoxic TILs and immunosuppressive TILs in TME • Density of signals of immune-cell-mediated killing in TME • Gene expression signatures of TME • Mutational status of tumors • Mutational burden of tumors • Select cytokine profiles in blood | — |
Countries
Netherlands
Outcome results
None listed