Metastatic or Locally Advanced Solid Tumors and Cervical Cancer MedDRA version: 21.1 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000004864
Conditions
Sponsors
Agenus Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 2: Female subjects over the age of 18 years with recurrent and/or metastatic cervical cancer who have relapsed after a platinum-based treatment regimen for advanced (recurrent, unresectable, or metastatic) disease. After the interim analyses, subsequent enrollment of subjects may be based on biomarker enrichment (including but not limited to PD-L1 expression). In such cases, tumor tissue must be positive for the selected entry biomarker prior to subject enrollment. 1. Voluntarily agree to participate by giving written informed consent. Participation in pharmacogenomics testing is optional. 3. Diagnosis and prior systemic treatment: b. Phase 2: I. Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) metastatic, locally advanced, and/or unresectable disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report. Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma. II. Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease; Note: Subject receiving chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or subject receiving adjuvant chemotherapy following completion of radiation therapy (e.g., paclitaxel and carboplatin for = 4 cycles) and progressed within 6 months after treatment completion will be eligible as this systemic therapy will be considered as first line treatment. 4. Measurable disease – based on investigator assessment b. Phase 2: Have measurable disease on imaging based on RECIST version 1.1. Note: Subjects must have at least one "target lesion" to be used to assess response, as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy. Note: Measurable disease by RECIST 1.1 must be confirmed by independent central radiologic review prior to first dose. Subjects without centrally confirmed measurable disease at baseline will not be eligible for this trial. 5. Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Have adequate organ function as indicated by the following laboratory values: a. Adequate hematological function defined by absolute neutrophil count (ANC) = 1.5 x 109/L, platelet count = 100 x 109/L, and stable hemoglobin = 8 g/dL (without transfusions within 1 week before first dose). b. Adequate hepatic function based by a total bilirubin level = 1.5 x the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level = 2.5 x IULN, alanine aminotransferase (ALT) level = 2.5 x IULN, and alkaline phosphatase = 2.5 x IULN. c. Adequate renal function defined as creatinine = 1.5 x IULN OR calculated creatinine clearance = 50 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). d. Adequate coagulation defined by international normalized ratio (INR) or prothrombin time = 1.5 x IULN (unless the subjec
Exclusion criteria
Exclusion criteria: 1. 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 before the first dose of treatment. 2. Has an inadequate washout period prior to first dose of study drug defined as: a. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose, b. Received radiation therapy within 3 weeks before first dose, or c. Had major surgery within 4 weeks before first dose. 3. Has received prior therapy with: a. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti–PD-1, anti–PD-L1, or anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies b. For Phase 2: > 1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the subject is considered for the study Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for subjects with metastatic melanoma. 4. Has persisting toxicity related to prior therapy of NCI CTCAE Grade > 1 severity. Note: Sensory neuropathy or alopecia of Grade = 2 is acceptable. 5. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection). 6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [NCI CTCAE] Grade = 3), any history of anaphylaxis, or uncontrolled asthma. 7. Is receiving systemic corticosteroid = 7 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events, and/or a premedication for IV contrast allergies/reactions is allowed). Subjects who are receiving daily corticosteroid replacement therapy are an exception to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5 mg or equivalent hydrocortisone dose, and steroid therapy administered by topical, intraocular, intranasal, and/or inhalation routes. 8. Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to consent. Note: Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (based on 2 sets of brain images, performed = 4 weeks apart, and obtained after the brain metastases treatment). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be minimal and be expected as sequelae from treated lesions. For individuals who received steroids as part of brain metastases treatment, steroids must be discontinued = 7 days prior to first dose of study drug. 9. Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of trial treatment (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 syst
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 - To assess the safety and tolerability of AGEN2034 in subjects with metastatic and/or locally advanced solid tumors Phase 2 - To assess objective response rate (ORR) according to RECIST 1.1 as determined by an Independent Endpoint Review Committee (IERC);Secondary Objective: Phase 1 • To characterize the AGEN2034 pharmacokinetic (PK) profile. • To correlate AGEN2034 exposure with target occupancy • To evaluate the immunogenicity of AGEN2034 and to correlate it to exposure Phase 2 • To assess the safety and tolerability of AGEN2034 in subjects with metastatic and/or locally advanced solid tumors • To characterize the AGEN2034 PK profile • To evaluate the immunogenicity of AGEN2034 and correlate it to exposure • To assess objective response rate (ORR) according to RECIST 1.1 as determined by investigator • To assess duration of response (DOR), disease control rate (DCR), duration of stable disease (SD), time to response, and progression-free survival (PFS) time per RECIST 1.1 • To assess overall survival (OS) rate • To assess OS time ;Primary end point(s): Phase 1 - Occurrence of DLTs in subjects in dose escalation during the first 21 days of treatment - Frequency, severity, and duration of treatmentemergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. Phase 2 - Confirmed ORR per RECIST 1.1, as determined by an IERC, in the analysis population;Timepoint(s) of evaluation of this end point: As per protocol section 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 - PK profile. - Receptor occupancy on circulating T cells measured 4 hours after the 1st dose and immediately prior to the 2nd dose - Receptor occupancy saturation levels correlated with AGEN2034 PK exposure metrics - Antidrug antibody (ADA) concentrations and correlation with AGEN2034 PK exposure metrics Phase 2 - Frequency, severity, and duration of TEAEs and laboratory abnormalities, using NCI CTCAE v4.03. - PK profile - ADA concentrations and correlation with AGEN2034 PK exposure metrics - Confirmed ORR per RECIST 1.1, as determined by an investigator - DOR per RECIST 1.1, as determined by an IERC and investigator, defined as time from first observation of response to first observation of documented disease progression (or death within 12 weeks after last tumor assessment). Subjects without an event at analysis cutoff date will be censored on date of last tumor assessment. - DCR, defined as proportion of subjects with complete response (CR), partial response (PR), or stable disease (SD) for at least 12 weeks - Duration of SD, measured from the start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline measurements. - Time to response, defined as the time from the first dose date to first observation of confirmed response. - PFS time, defined as time from first treatment administration to first observation of documented disease progression (or death within 12 weeks after last tumor assessment), per RECIST 1.1, as determined by an IERC and investigator. Subjects without an event at analysis cutoff date will be censored on date of last tumor assessment. - Median OS and OS rate - OS time, defined as time from start of treatment to death. For subjects who are still alive at time of data cutoff for trial analysis or who are lost to follow-up, survival will be censored at the last recorded date that the subject is | — |
Countries
Australia, Belgium, Brazil, Estonia, France, Lithuania, Poland, Spain, United States
Contacts
Public ContactRim Imam
Agenus Inc.
Outcome results
None listed