Phase 1 – Part A dose escalation in patients with locally advanced, recurrent and/or metastatic solid tumor for which no standard therapy exists or standard therapy has failed. Phase 2 - Part B advanced cervical cancer MedDRA version: 21.1 Level: LLT Classification code 10008236 Term: Cervical cancer stage IV System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000004864 MedDRA version: 21.1 Level:
Conditions
Interventions
Product Code: AGEN2034
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: AGEN2034
Current Sponsor code: AGEN2034
Other descriptive name: AGEN2034
Concentration unit: mg/ml milligram(s)/m
Sponsors
Agenus Inc.,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntarily agree to participate by giving written informed consent. Participation in pharmacogenomics testing is optional. 2. =18 years of age. 3. Diagnosis: a. Phase 1 – Male or female having histologically or cytologically confirmed diagnosis of a locally advanced, recurrent, and/or metastatic solid tumor for which no standard therapy is available or standard therapy has failed. b. Phase 2 - I. Female having (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) locally advanced, recurrent, and/or metastatic 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 locally advanced, recurrent, and/or metastatic disease; Note: Subjects who only received platinum-based chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or 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 first line. 4. Measurable Disease a. Phase 1: objective evidence of disease; presence of measurable disease is not required. b. Phase 2: measurable disease on imaging based on RECIST version 1.1. 5. life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. adequate organ function as indicated by laboratory values. 7. Other than the cancer for which the subject is enrolled, no history of prior malignancy, with exception of basal cell carcinoma of skin, superficial bladder cancer, squamous-cell carcinoma of skin, or undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. 8. In Phase 2, sufficient and adequate formalin fixed tumor tissue sample. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. 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 first dose of treatment. 2. received 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 locally advanced, recurrent, and/or metastatic cervical cancer for which the subject is considered for the study. Subjects who received a systemic regimen immediately after progressing within 6 months of completing chemotherapy concurrent with primary radiation or adjuvant chemotherapy after radiation will only be considered as having 1 prior systemic regimen for the purpose of this criterion. 4. persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCICTCAE) Grade >1 severity. 5. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, adiation therapy, and/or surgical resection). 6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 4.03 Grade =3), any history of anaphylaxis, or uncontrolled asthma 7. Is receiving systemic corticosteroid therapy = 7 days prior to the first dose of study treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related AEs, 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 study 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 adren
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: • assess safety and tolerability of AGEN1884 in combination with AGEN2034 in subjects with locally advanced, recurrent and/or metastatic solid tumors. Phase 2: • Phase 2: To assess ORR (objective Response rate) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the IERC.;Secondary Objective: Phase 1: • characterize pharmacokinetic (PK) profiles of AGEN1884 and AGEN2034 • correlate AGEN1884 and AGEN2034 exposure with target occupancy • evaluate immunogenicity of AGEN1884 in combination with AGEN2034 and assess potential impact on PK exposure and biological activity Phase 2: • assess the safety and tolerability of AGEN1884 in combination with AGEN2034 in subjects with locally advanced, recurrent, and/or metastatic solid Tumors • characterize PK profile of AGEN1884 and AGEN2034 • evaluate immunogenicity of AGEN1884 in combination with AGEN2034 and assess potential impact on PK exposure and biological activity • assess ORR according to RECIST 1.1 as determined by investigator • assess DOR, disease control rate (DCR), duration of SD, time to response, and PFS time per RECIST 1.1 • assess OS;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 treatment-emergent AEs (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.Occurrence of DLTs in subjects in dose escalation during the first 21 days of treatment. Phase 2: •Confirmed ORR per RECIST 1.1, as determined by the IERC, in the analysis population.;Timepoint(s) of evaluation of this end point: • Phase 1: during the first 21 days of treatment. • Phase 2: throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1: • AGEN1884 and AGEN2034 PK parameters which may include (but are not limited to) maximum observed concentration at steady-state (Cmax-ss), minimum observed concentration at steady-state (Cmin-ss), area under the drug concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss), area under the drug concentration-time curve from time zero to time t (AUC(0-t)), area under the drug concentration-time curve from time zero to infinity (AUC(0-8)), time to maximum observed concentration (tmax), terminal disposition rate constant (?z), terminal elimination half-life (t1/2), systemic clearance (CL), and volume of distribution (Vd) • Receptor occupancy on circulating T cells measured 4 hours after the first dose and immediately prior to the second dose • Receptor occupancy saturation levels correlated with AGEN1884 and GEN2034 PK exposure metrics • ADA concentrations and potential impact on AGEN1884 and AGEN2034 PK exposure metrics Phase 2: • Frequency, severity, and duration of TEAEs and laboratory abnormalities, using NCI-CTCAE v4.03. • AGEN1884 and AGEN2034 PK parameters which may include (but are not limited to) Cmax-ss, Cmin-ss, AUC(t1-t2)-ss, AUC(0-t), AUC(0-8), tmax, ?z, t1/2, L, and Vd. • ADA concentrations and potential impact on AGEN1884 and 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 be censored on date of last tumor assessment. • DCR, defined as proportion of subjects with CR, PR, or 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 fir | — |
Countries
Australia, Brazil, Hungary, Poland, Spain, Ukraine, United States
Outcome results
None listed