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Anti-CD137 Monoclonal Antibody in Patients With Advanced Cancer

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ClinicalTrials.gov Identifier: NCT04121676
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Agenus Inc.

Brief 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 Balstilimab (AGEN2034), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: AGEN2373 Drug: Balstilimab (AGEN2034) Phase 1

Detailed Description:

This Phase 1 study will enroll up to approximately 86 evaluable adult subjects with refractory cancer (solid tumors) regardless of diagnosis. Subjects may be enrolled into the following cohorts:

The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN2373 monotherapy and in combination with Balstilimab (AGEN2034). Each subject will stay on the dose level at a schedule assigned at trial entry. Subjects can be replaced for any reason other than a DLT. Subjects will receive treatment for ≤ 2 years or until PD, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal of trial occurs.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of AGEN2373, an Anti-CD137 Monoclonal Antibody, as Monotherapy and in Combination With Balstilimab (AGEN2034), an Anti-PD-1 Monoclonal Antibody in Patients With Advanced Cancer
Actual Study Start Date : September 12, 2019
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: 4-Week Monotherapy with AGEN2373
3+3 Dose escalation of AGEN2373 administered by IV.
Drug: AGEN2373
An Anti-CD137 Monoclonal Antibody
Other Name: Anti-CD137

Experimental: 2-Week Monotherapy with AGEN2373
3+3 Dose escalation of AGEN2373 administered by IV.
Drug: AGEN2373
An Anti-CD137 Monoclonal Antibody
Other Name: Anti-CD137

Experimental: 2-Week Combination Therapy with AGEN2373 and AGEN2034
3+3 Dose escalation of AGEN2373 in combination with Balstilimab (AGEN2034) administered by IV.
Drug: AGEN2373
An Anti-CD137 Monoclonal Antibody
Other Name: Anti-CD137

Drug: Balstilimab (AGEN2034)
Balstilimab (AGEN2034) A fully human monoclonal Anti-PD-1 Antibody. (AGEN2373) An Anti-CD137 Monoclonal Antibody
Other Names:
  • Anti-PD-1
  • AGEN2373
  • Anti-CD137




Primary Outcome Measures :
  1. Occurrence of Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]
    DLT in subjects in dose escalation phase


Secondary Outcome Measures :
  1. Frequency of treatment-emergent adverse events (TEAEs) [ Time Frame: Screening to 90 days from last dose ]
    According to NCI-CTCAE Version 5.0

  2. Severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Screening to 90 days from last dose ]
    According to NCI-CTCAE Version 5.0

  3. Duration of treatment-emergent adverse events (TEAEs) [ Time Frame: Screening to 90 days from last dose ]
    According to NCI-CTCAE Version 5.0

  4. Maximum observed concentration at steady state (Cmax-ss) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  5. Minimum observed concentration at steady state (Cmin-ss) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  6. area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  7. area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t)) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  8. area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞)) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  9. time to maximum observed concentration (tmax) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  10. terminal disposition rate constant (λz) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  11. terminal elimination half-life (t1/2) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  12. systemic clearance (CL) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  13. volume of distribution (Vd) [ Time Frame: Day 1 of dosing through 90 days from the last dose ]
    PK Profile of AGEN2373 and AGEN2034

  14. Immunogenicity of AGEN2373 and AGEN2034 [ Time Frame: Predose through 3 months after the last dose. ]
    ADA Profile of AGEN2373 and AGEN2034

  15. Overall Response Rate (ORR) [ Time Frame: Evaluated throughout the protocol up to 2 years ]
    per RECIST 1.1

  16. Duration of Response (DOR) [ Time Frame: First observation of documented disease progression (or death within 12 weeks of the last tumor assessment). ]
    per RECIST 1.1

  17. Disease Control Rate (DCR) [ Time Frame: 24 weeks of first dose ]
    including complete and partial responders and stable disease [SD] for at least 12 weeks per RECIST 1.1

  18. Progression Free Survival (PFS) [ Time Frame: First treatment administration to first observation of documented disease progression (or death within 12 weeks of last tumor assessment). ]
    median and/or rate as defined in the statistical analysis plan



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional.
  2. ≥18 years of age.
  3. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
  4. Measurable disease on imaging based on RECIST Version 1.1.
  5. Life expectancy of ≥ 3 months and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Adequate organ and bone marrow reserve function, as indicated by the following laboratory values:

    1. Adequate hematological function, defined as absolute neutrophil count ≥ 1.5 × 109 /L, platelet count ≥ 100 × 109 /L, and hemoglobin ≥ 8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement).
    2. Adequate liver function, defined as total bilirubin level ≤ 1.5 × institutional upper limit of normal (IULN), aspartate aminotransferase ≤2.5 × IULN, and alanine aminotransferase ≤ 2.5 × IULN.
    3. Adequate renal function defined as creatinine ≤ 1.5 × IULN OR calculated creatinine clearance ≥ 40 mL/minute per institutional standard. Assessment methods should be recorded.
    4. Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × IULN and activated partial thromboplastin time ≤ 1.5 × IULN (unless patient receiving anticoagulant therapy).
  7. No history of prior or concomitant malignancy that requires other active treatment.
  8. Patients must provide sufficient and adequate formalin-fixed paraffin-embedded tumor tissue sample (fresh biopsy) collected within 28 days before the first dose from a site not previously irradiated and to agree to a mandatory on-treatment biopsy if clinically feasible.
  9. 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:

    1. ≥ 45 years of age and has not had menses for > 1 year.
    2. Amenorrheic for > 2 years without a hysterectomy and oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon prestudy (screening) evaluation.
    3. Status is post-hysterectomy, -oophorectomy, or -tubal ligation.
  10. 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 for the patient.

  11. 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.

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 3 weeks of first dose of current study treatment.
  2. Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with Sponsor approval.
  3. Patients who have received prior therapy with any anti-CD137 monoclonal antibody or agent may be enrolled in selected indications upon agreement with the Sponsor.

    Note: Selected cohorts may accept prior therapy with an anti-CD137 antibody or agent.

  4. Persistent toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) Grade > 1 severity that is related to prior therapy.

    Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.

  5. Expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
  6. Known severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids; or has a history of interstitial lung disease, any history of anaphylaxis, or uncontrolled asthma. (i.e. ≥ 3 features of partly controlled asthma or pneumonitis that has required oral or intravenous [IV] corticosteroids).
  7. Receiving systemic corticosteroid therapy 1 week prior to the first dose of study treatment or receiving 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 ≤ 7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted.

  8. 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.

  9. 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 diabetes type 1, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

  10. Has had an allogeneic tissue/solid organ transplant except for corneal transplantation.
  11. Active infection requiring treatment.
  12. Known history of HIV type 1 or 2 antibodies.
  13. Current or chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) defined as:

    • Positive test for hepatitis B surface antigen indicating active or chronic infection. Note: Patients with previous history of HBV (who have cleared the infection and have natural immunity, i.e. hepatitis B core antibody positive cases) are excluded.
    • Positive test for (HCV)RNA indicating active or chronic infection. Note: Patients with positive HCV antibody and negative HCV by polymerase chain reaction are eligible.
  14. Clinically significant (i.e. 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.
  15. 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.
  16. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  17. Legally incapacitated or has limited legal capacity.
  18. Pregnant or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04121676


Contacts
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Contact: Agenus, Inc. Clinical Trial Information 781-674-4265 clinicaltrialinfo@Agenusbio.com

Locations
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United States, California
University of Southern California Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Xiomara Menendez    323-865-0212    clinical.trials@med.usc.edu   
Principal Investigator: Anthony El-Khoueiry, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Lisa Olmos    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Richard Carvajal, MD         
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75230
Contact: Mary Crowley Referral Office    972-566-3000    referral@marycrowley.org   
Principal Investigator: James Strauss, MD         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Sarah Gomez    210-580-9521    sgomez@nextoncology.com   
Principal Investigator: Anthony Tolcher, MD         
Sponsors and Collaborators
Agenus Inc.
Investigators
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Study Director: Medical Director Agenus Inc.
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Responsible Party: Agenus Inc.
ClinicalTrials.gov Identifier: NCT04121676    
Other Study ID Numbers: C-1100-01
First Posted: October 10, 2019    Key Record Dates
Last Update Posted: March 2, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Agenus Inc.:
Solid tumors
Anti-CD137
Advanced Cancer
Open-Label
Dose Escalation
Monotherapy
Combination Therapy
Anti-PD-1
Additional relevant MeSH terms:
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Neoplasms