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Clinical Trial 21741

Cancer Type: Cutaneous
Study Type: Treatment
NCT#: NCT04121676

Phase: Phase I
Principal Investigator: Tarhini, Ahmad

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Study Title

A Phase 1 Study of AGEN2373, an Anti-CD137 Monoclonal Antibody, as Monotherapy and in Combination with AGEN1181, an Fc-Enqineered Anti-CTLA-4 Monoclonal Antibody, in Patients with Advanced Cancer


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.


- To assess the safety, tolerability, and dose-limiting toxicity (DLT) of AGEN2373 asmonotherapy and in combination withAGEN1181 - To determine the recommended Phase 2 dose(RP2D) for AGEN2373 monotherapy andAGEN2373 in combination with AGEN1181





AGEN1181 (); AGEN2373 ()

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 > 3 months and ECOG performance status of 0 or 1.
  • Adequate organ and bone marrow reserve function, as define by protocol
  • Patients with a history of prior malignancy are eligible if treatment was completed ≥ 2 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 biopsy collected after the last dose of prior anti-cancer therapy and before the first dose of study treatment from a site not previously irradiated and agree to mandatory on-treatment biopsy if clinically feasible.
  • 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.
  • Specific Melanoma Criteria:
  • Note: these specific criteria below are in addition to the general criteria above and supersede the general criteria in some cases.
  • 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
  • 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
  • History of (a) Severe (Grade >3) hypersensitivity reactions to fully human monoclonal antibodies, (b) immune-related adverse event requiring treatment with systemic steroids for > 7 days (refer to Exclusion Criterion #7 for exceptions) excluding Grade 1 or 2 rash; (c) interstitial lung disease or lung disease which may interfere with the assessment of pneumonitis; (d) uncontrolled 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 > 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 (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.
  • Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Patients with autoimmune conditions requiring hormone replacement therapy or topical treatment are eligible.
  • Has had an allogeneic tissue/solid organ transplant except for corneal transplantation.
  • Active infection requiring systemic treatment.
  • Active infection with HIV. Patients not on established antiretroviral therapy for at least 4 weeks and having a detectable HIV viral load. Testing is not required for eligibility.
  • Active infection with hepatitis B (surface antigen); or infection with hepatitis C, defined by a detectable viral load. Testing is required for eligibility only if patient has a known or suspected history of infection.
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure, or serious uncontrolled cardiac arrhythmia requiring medication
  • Additional Criteria will apply

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