Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patient With Advanced Cancer

  • STATUS
    Recruiting
  • End date
    Jun 24, 2027
  • participants needed
    200
  • sponsor
    Agenus Inc.
Updated on 24 July 2022
platelet count
renal function
measurable disease
carcinoma
anticoagulants
squamous cell carcinoma
anticoagulant therapy
neutrophil count
aptt
solid neoplasm
bladder cancer, squamous cell carcinoma
bladder cancer

Summary

This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in combination with botensilimab (also known as AGEN1181), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Description

This Phase 1 study will enroll up to approximately 200 evaluable adult patients with a histologically confirmed diagnosis of advanced cancer for which no standard therapy is available or standard therapy has failed, regardless of diagnosis and prior therapies. This also includes patients with PD-1/PD-L1 R/R melanoma. Patients may be enrolled into one of 5 treatment arms:

2-Week AGEN2373 monotherapy

3-Week AGEN2373 monotherapy

4-Week AGEN2373 monotherapy

Combination of AGEN2373 and botensilimab in patients with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) relapsed/refractory (R/R) melanoma.

Group 1 (Monotherapy Lead-in Combination): Q3W AGEN2373 lead-in followed by Q3W AGEN2373 in combination with Q6W botensilimab. (AGEN2373 will be administered on Day 1 every 3 weeks. Starting with Cycle 4 Day 1, botensilimab will be added as combination therapy and administered every other cycle (Cycles 4, 6, 8, 10, etc.). (Botensilimab is administered every 6 weeks.)

Group 2 (Combination): AGEN2373 will be administered Q3W in combination with botensilimab administered every other cycle. (Botensilimab is administered every 6 weeks.)

The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN2373 monotherapy and in combination with botensilimab. Each patient will stay on the dose level and schedule assigned at trial entry. Patients will receive treatment for ≤ 2 years (i.e., maximum of 34 cycles) (AGEN2373) as monotherapy and botensilimab ≤ 1 year (i.e., maximum of 8 doses) as combination therapy with AGEN2373 ≤ 2 years (i.e., maximum of 34 cycles), or until progressive disease, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal of trial occurs.

Patients who do not complete the DLT observation period (28 days for the 2-Week and 4-Week AGEN2373 Monotherapy arms and 21 days for the 3-Week AGEN2373 Monotherapy and Combination arms) after the first dose for reasons other than DLT will be replaced.

Details
Condition Advanced Cancer
Treatment AGEN1181, AGEN2373, Balstilimab (AGEN2034), Botensilimab
Clinical Study IdentifierNCT04121676
SponsorAgenus Inc.
Last Modified on24 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional
≥ 18 years of age
Histologically or cytologically confirmed diagnosis of a solid tumor that is currently metastatic or locally advanced for which no standard therapy is available or standard therapy has failed
Measurable disease on imaging based on RECIST 1.1
Life expectancy of ≥ 3 months and ECOG performance status of 0 or 1
Adequate organ and bone marrow reserve function, as indicated by the following laboratory values
Adequate hematological function, defined as absolute neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 10^9/L, and hemoglobin ≥ 8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement)
Adequate liver function, defined as total bilirubin level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase ≤ 2.5 × ULN, and alanine aminotransferase ≤ 2.5 × ULN, albumin ≥ 3 g/dL, and alkaline phosphatase ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
Adequate renal function defined as creatinine ≤ 1.5 × ULN OR measured or calculated creatinine clearance ≥ 40 mL/minute per institutional standard. Assessment methods should be recorded
Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN (unless patient is receiving anticoagulant therapy)
Patients with a history of prior malignancy are eligible if treatment was completed ≥
years prior to the first dose of study treatment and the patient has no
evidence of disease
Patients must provide a sufficient and adequate formalin-fixed paraffin-embedded tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a site not previously irradiated. If no tumor tissue is available, a fresh biopsy will be required
Female patients of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following
≥ 45 years of age and has not had menses for > 1 year
Amenorrheic for > 2 years without a hysterectomy and oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon prestudy (screening) evaluation
Status is post-hysterectomy, -bilateral oophorectomy, or -tubal ligation
Female patients of childbearing potential must be willing to use highly effective
contraceptive measures starting with the Screening Visit through 90 days after
last dose of study treatment. Note: Abstinence is acceptable if this is the
established and preferred contraception method for the patient
Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the Screening Visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient
Note: these specific criteria below are in addition to the general criteria above and
supersede the general criteria in some cases
Specific Melanoma Criteria
Inclusion
Histological confirmation of cutaneous melanoma
Progression on or within 24 weeks of stopping treatment with a PD-1/PD-L1 confirmed
per Society for Immunotherapy of Cancer (SITC)
Patients with BRAF V600-positive tumor(s) should also have received prior treatment
with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or have declined
targeted therapy
Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related
symptoms nor evidence of rapidly progressive disease are not required to be treated with a
BRAF inhibitor (alone or in combination with a MEK inhibitor) based on Investigator's
decision

Exclusion Criteria

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 3 weeks of first dose of current study treatment
Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or
major surgery outside of the acceptable washout period prior to first dose of study
drug. A 1-week washout is permitted for palliative radiation to non-central nervous
The following washout windows are acceptable from prior treatments (i.e., patients
system (CNS) disease, with Sponsor approval
with time periods less than the following should be excluded)
Cytotoxic agent ≥ 3 weeks is acceptable (i.e., < 3 weeks should be excluded)
Monoclonal antibodies ≥ 4 weeks is acceptable (i.e., < 4 weeks should be
excluded)
Proteasome inhibitors or corticosteroids ≥ 2 weeks is acceptable (i.e., < 2 weeks
should be excluded)
Small molecule/tyrosine kinase inhibitor within 14 days or less than 5
circulating half-lives of investigational drug
Having a previous SARS-CoV-2 vaccine > 7 days before administration. For vaccines
requiring more than 1 dose, the full series should be completed prior to Cycle 1
Day 1, when feasible, and when the delay in initiation of study treatment would
not put the study patients at risk
Patients who have received prior anti-CD137 therapy may be enrolled upon agreement
with the Sponsor
Persistent toxicity of NCI-CTCAE version 5.0 Grade > 1 severity that is related to
prior therapy. Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable
Expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent, radiation therapy
History of (a) Severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal
and/or surgical resection)
antibodies, (b) immune-related adverse event requiring treatment with systemic
steroids for > 7 days (refer to Exclusion Criterion #7 for exceptions) excluding Grade
or 2 rash; (c) interstitial lung disease or lung disease which may interfere with
the assessment of pneumonitis; (d) uncontrolled asthma. (i.e., ≥ 3 features of partly
controlled asthma); and (e) or pneumonitis that has required oral or IV
corticosteroids)
Receiving systemic corticosteroid therapy per Exclusion Criterion #2, or any other
form of systemic immunosuppressive medication. Note: Corticosteroid use as a
premedication for IV contrast allergies/reactions is allowed. Patients who are
receiving daily corticosteroid replacement therapy are also an exception to this rule
Daily prednisone at doses of ≤ 10 mg or equivalent hydrocortisone dose are examples of
permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted
CNS tumor, metastasis(es), and/or carcinomatous meningitis identified either on the
consent. Note: Patients with history of brain metastases that have been treated may
baseline brain imaging obtained during the Screening Period or identified prior to
participate provided they show evidence of stable supra-tentorial lesions at screening
(defined as 2 brain images, both of which are obtained after treatment to the brain
metastases and obtained ≥ 4 weeks apart). In addition, any neurologic symptoms that
developed either as a result of the brain metastases or their treatment must have
returned to baseline or resolved. Any steroids administered as part of this therapy
must be completed ≥ 3 days prior to first dose of study medication
years of the start of study treatment (i.e., with use of disease-modifying agents
corticosteroids, or immunosuppressive drugs). Note: Patients with autoimmune
Active or history of autoimmune disease that requires systemic treatment within 2
conditions requiring hormone replacement therapy or topical treatment are eligible
Active infection requiring systemic treatment
Has had an allogeneic tissue/solid organ transplant except for corneal
transplantation
Active infection with HIV and CD4+ T-cell count <350/μL. Patients not on established
defined by a detectable viral load. Testing is required for eligibility only if
antiretroviral therapy for at least 4 weeks and having a detectable HIV viral load
patient has a known or suspected history of infection
Testing is not required for eligibility
Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
Active infection with hepatitis B (surface antigen); or infection with hepatitis C
accident/stroke or myocardial infarction within 6 months of enrollment, unstable
angina, congestive heart failure (New York Heart Association class ≥ II), or serious
uncontrolled cardiac arrhythmia requiring medication
History or current evidence of any condition, therapy, any active infections, or
laboratory abnormality that might confound the results of the study, interfere with
the patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating Investigator
Known psychiatric or substance abuse disorder that would interfere with cooperation
with the requirements of the study
Legally incapacitated or has limited legal capacity
Pregnant or breastfeeding
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