NCT03411473
Terminated
Phase 2
A Phase IIa Open-Label Trial of AGEN1884 in Combination With Pembrolizumab in Subjects With Chemotherapy Naïve, PD-L1 High, Metastatic Non-Small Cell Lung Cancer (NSCLC)
ConditionsNSCLC Stage IV
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Agenus Inc.
- Enrollment
- 2
- Locations
- 5
- Primary Endpoint
- Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial
Overview
Brief Summary
A Phase IIa Open-Label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination with Pembrolizumab in Subjects with Chemotherapy Naïve, PD-L1 high, metastatic Non-Small Cell Lung Cancer (NSCLC)
Detailed Description
This is a Phase IIa, open-label study, of AGEN1884 in combination with pembrolizumab in subjects with stage IV NSCLC whose tumors have high PD-L1 expression and no EGFR or ALK genomic tumor aberrations.
The study consists in two phases:
- Safety Run-in Phase
- Efficacy Phase
Subjects will be enrolled in a "3+3" Safety Run-in followed by enrollment completing the efficacy cohort. Two different dose levels of AGEN1884 may be tested in combination with the approved pembrolizumab treatment for this indication (until disease progression, unacceptable toxicity, or up to a maximum of 24 months). Each subject will stay on the dose level assigned at trial entry.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily agree to participate.
- •Be ≥18 years of age.
- •Have a histologically or cytologically confirmed diagnosis of NSCLC, is stage IV, does not have an EGFR sensitizing (activating) mutation or ALK translocation, and has not received prior systemic chemotherapy treatment for their metastatic NSCLC.
- •Have measurable disease based on RECIST 1.1 as determined by the site.
- •Have a life expectancy of at least 3 months and a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
- •Have adequate organ function as indicated by the following laboratory values:
- •Adequate hematological function defined by absolute neutrophil count (ANC) \> 1.5 x 109/L, platelet count \> 100 x 109/L, and hemoglobin \> 9 g/dL (without transfusions within 2 weeks of first dose).
- •Adequate hepatic function based by a total bilirubin level \< the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level \< 1.5 x IULN, alanine aminotransferase (ALT) level \< 1.5 x IULN, and alkaline phosphatase ≤ 2.5 ULN.
- •Adequate renal function defined as Creatinine ≤ 1.5 x IULN OR calculated creatinine clearance \> 60 mL/min for subjects with creatinine levels \> 1.5 x IULN (If no local guideline is available, creatinine clearance should be calculated using the Cockcroft-Gault Method).
- •Adequate coagulation defined by international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy)
Exclusion Criteria
- •Has an EGFR sensitizing mutation and/or an ALK translocation.
- •Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
- •Is receiving systemic steroid therapy \< 3 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication.
- •Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
- •Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of \> 30 Gy within 6 months of the first dose of trial treatment.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •Has central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to signing the ICF.
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Has had an allogeneic tissue/solid organ transplant.
Outcomes
Primary Outcomes
Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial
Time Frame: 21 days
Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial
Secondary Outcomes
- PFS time(36 months)
- Duration of response per RECIST 1.1(36 months)
- Unconfirmed response at 12 weeks from first dose per RECIST 1.1(Up to 24 months from 1st dose of treatment)
- Pharmacokinetic profile of AGEN1884 and pembrolizumab(At least 20 patients have completed 12 weeks from 1st dose of treatment)
- Frequency, severity, and duration of treatment-emergent AEs (TEAEs)(116 weeks)
- Frequency, severity, and duration of treatment-related AEs(116 weeks)
- Confirmed BOR per RECIST 1.1(116 weeks)
- OS time(June 2020 ( When 14 patients have completed 2 years of treatment))
- Immunogenicity of AGEN1884 and pembrolizumab(All patients on study have completed 6 weeks from 1st dose of treatment)
Investigators
Study Sites (5)
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