Fc-Engineered Anti-CTLA-4 Monoclonal Antibody in Advanced Cancer

Running, not enrolling · Phase 1

Conditions studied: Advanced Cancer, Angiosarcoma, Colorectal Cancer Without Liver Metastases, Endometrial Cancer, Fibrolamellar Carcinoma, Non-small-cell Lung Cancer, Ovarian Cancer, Prostate Cancer

In brief

This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) profiles of a novel fragment crystallizable (Fc)-engineered immunoglobulin G1 anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) human monoclonal antibody (botensilimab) monotherapy and in combination with an anti-programmed cell death protein-1 (PD-1) antibody (balstilimab), and to assess the maximum tolerated dose (MTD) in participants with advanced solid tumors. This study will also determine the recommended phase 2 dose (RP2D) of botensilimab monotherapy and in combination with balstilimab.

Key facts

Study ID: NCT03860272
Run by: Agenus Inc.
People needed: 499
Starts: 2019-03-20
Expected to finish: 2027-12-01
Last updated by the study team: 2026-03-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

For inclusion in the trial, all of the following inclusion criteria must be fulfilled, as no waivers will be permitted:
Provision of signed and dated written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional.
Histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
Measurable disease on imaging based on RECIST 1.1, except for prostate cancer.
Life expectancy of ≥ 3 months and Eastern Cooperative Oncology Group 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/liter (L), platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 8 grams/deciliter 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 × institutional upper limit of normal (IULN) (except for participants with Gilbert syndrome who must have a total bilirubin level of ≤ 3.0 × IULN), aspartate aminotransferase ≤ 2.5 × IULN, and alanine aminotransferase ≤ 2.5 × IULN.
Adequate renal function defined as creatinine ≤ 1.5 × IULN or measured or calculated creatinine clearance ≥ 40 milliliters (mL)/minute per institutional standard. Assessment methods should be recorded.
Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × IULN and activated partial thromboplastin time ≤ 1.5 × IULN (unless participant receiving anticoagulant therapy) or stable known coagulopathy with sponsor approval.
A sufficient and adequate formalin-fixed paraffin embedded tumor tissue sample (fresh or archival tumor tissue) collected since last treatment and before the first dose from a site not previously irradiated, if clinically feasible.
Female participants 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 and there is no alternative medical cause.
Amenorrheic for > 2 years without a hysterectomy and/or oophorectomy and follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation.
Status is post-hysterectomy, -oophorectomy, or -tubal ligation.
Female participants 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. For the UK only, highly effective contraceptive measures are defined as follows:
Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation.
Oral
Intravaginal
Transdermal
Progesterone-only hormonal contraception associated with inhibition of ovulation.
Oral
Injectable
Implantable
Intrauterine device

You may not qualify if…

For inclusion in the trial, participant must meet none of the following exclusion criteria, as no waivers will be permitted:
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 drug.
Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study drug; for tyrosine kinase inhibitor or similar within 4 × half-life prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system disease, with Sponsor approval.
Participants who have received prior CTLA-4 therapy may be enrolled in selected indications 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, hypothyroidism or alopecia of Grade ≤ 2 are acceptable. Other Grade 2 toxicities of prior treatments that are controlled with medication (for example, diabetes or hypertension) may be permitted with sponsor approval.
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).
History of:
Severe (Grade ≥ 3) hypersensitivity reaction to a fully human monoclonal antibodies
Immune-related adverse event requiring treatment with systemic steroids for > 7 days excluding Grade 1 or 2 rash.
Interstitial lung disease or lung disease which may interfere with the assessment of pneumonitis.
Uncontrolled asthma (that is, ≥ 3 features of partly controlled asthma)
Pneumonitis that has required oral or IV corticosteroids.
Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication. Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Participants who are receiving daily corticosteroid replacement therapy are also an exception to this rule. Daily prednisone at doses of ≤ 7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted.
Brain metastases or leptomeningeal metastases with the following exceptions: Note: Brain metastases which have been treated with either surgical resection or stereotactic radio surgery. These participants must be off steroids ≥ 10 days prior to enrollment for the purpose of managing their brain metastases. Repeat brain imaging following surgical resection or stereotactic radiosurgery is not required if their last brain magnetic resonance imaging is within screening window. Note: Untreated isolated brain metastases that are too small for treatment by surgical resection or stereotactic radiosurgery (that is, 1-2 mm) and/or of uncertain etiology are potentially eligible but must be approved by the sponsor.
Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study drug (that is, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Participants with autoimmune conditions requiring hormone replacement therapy or topical treatments are eligible.
Has had an allogeneic tissue/solid organ transplant, except for corneal transplants.
Active infection requiring systemic treatment.
Known history of human immunodeficiency virus type 1 or 2 antibodies.
Known active infection with hepatitis B and/or hepatitis C virus.
Clinically significant (that is, active) cardiovascular disease: cerebral vascular 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 trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant 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.
Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment. Exceptions: participants with completely resected prior early-stage basal/squamous cell skin cancer or treated cervical carcinoma in situ.

Where it is running

HonorHealth Research Institute — Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center — Duarte, California, United States
The Angeles Clinic & Research Institute, a Cedars-Sinai Affiliate — Los Angeles, California, United States
University of Southern California Norris Comprehensive Cancer Center — Los Angeles, California, United States
UCLA Santa Monica Hematology Oncology — Los Angeles, California, United States
Saint John's Cancer Institute — Santa Monica, California, United States
University of Colorado — Aurora, Colorado, United States
Yale Cancer Center — New Haven, Connecticut, United States
University of Miami Sylvester Comprehensive Cancer Center — Miami, Florida, United States
Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai — New York, New York, United States
Columbia University Medical Center — New York, New York, United States
Memorial Sloan Kettering Cancer Center — New York, New York, United States
Providence Portland Cancer Center — Portland, Oregon, United States
MD Anderson Cancer Center — Houston, Texas, United States
The University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States
Royal Marsden Hospital NHS Foundation Trust — London, United Kingdom

Full record on ClinicalTrials.gov

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