PHASE 2 STUDY OF AGEN2034 AS MONOTHERAPY OR IN COMBINATION THERAPY WITH AGEN1884 IN SECOND-LINE CERVICAL CANCER
- Conditions
- -C53 Malignant neoplasm of cervix uteriMalignant neoplasm of cervix uteriC53
- Registration Number
- PER-047-19
- Lead Sponsor
- Agenus Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional)
2. Be ≥18 years of age
3. Diagnosis:
a. 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.
b. Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease;
Note: Patient receiving chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or patient 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
a) Have measurable disease on imaging based on RECIST version 1.1 by investigator assessments.
Note: Patients 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.
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 hemoglobin >8 g/dL (without transfusions within 1 week of first dose).
b) Adequate hepatic function based by a total bilirubin level ≤ 1.5 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 IULN and albumin ≥3.0 mg/dL.
c) Adequate renal function defined as calculated creatinine clearance >50 mL/min (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 patient is receiving anticoagulant therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the patient is receiving anticoagulant therapy)
7. Have no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous-cell carcinoma of the skin, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
Note: The history and time requirement for no evidence of disease for 5 years does not apply to the cancer for which the patient is enrolled in the study.
8. Patients must provide a sufficient and adequate formalin-fixed paraffin embedded (FFPE) tumor tissue sample preferably from t
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 of 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. More than 1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the patient is considered for the study.
4. Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (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 (NCI-CTCAE Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
7. Has received systemic corticosteroid therapy ≤ 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 (AE), and/or a premedication for IV contrast allergies/reactions is allowed). Patients who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of up to 5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
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: Patients 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 immunosuppressive 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 immunosuppressive systemic treatment.
Note: Patients with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyro
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Quantified as the binomial proportion of ITT patients with a BOR of CR or PR. BOR for each patient will be determined by the IRRC, according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).<br>Measure:The ORR for each treatment arm will be quantified as the binomial proportion of patients with a BOR of CR or PR on the ITT analysis set.<br>Timepoints:Study duration<br>
- Secondary Outcome Measures
Name Time Method