Clinical Trials /

AGEN2034 & AGEN1884 in Patients With Recurrent, Inoperable Angiosarcoma

NCT04607200

Description:

This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic Angiosarcoma (AS).

Related Conditions:
  • Angiosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AGEN2034 & AGEN1884 in Patients With Recurrent, Inoperable Angiosarcoma
  • Official Title: A Phase 2 Study Examining AGEN2034 as a Single-Agent and in Combination With AGEN1884 in Patients With Recurrent, Inoperable Angiosarcoma

Clinical Trial IDs

  • ORG STUDY ID: C-550-02
  • NCT ID: NCT04607200

Conditions

  • Angiosarcoma

Interventions

DrugSynonymsArms
AGEN2034Anti-PD-1Combination Therapy
AGEN1884Anti-CTLA-4Combination Therapy

Purpose

This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic Angiosarcoma (AS).

Detailed Description

      This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent
      AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or
      metastatic AS.

      Three cohorts will be enrolled into 2 Parts of the study as follows:

      Part 1

        -  Cohort 1: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into
           single-agent AGEN2034

        -  Cohort 2: Qualifying patients that are inhibitor (PD-1/L1) resistant will be enrolled
           into combination AGEN2034 + AGEN1884

      Part 2

      • Cohort 3: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into
      combination AGEN2034 + AGEN1884. Part 2 will begin enrollment after enrollment in Part 1 is
      completed

      The study will be conducted in 2 parts:

      In Part 1, checkpoint inhibitor naïve patients will be treated with single-agent AGEN2034
      (Cohort 1) and patients resistant to PD-1/PD-L1 (defined as prior progression on PD 1/PD-L1
      treatment) will be treated with combination of AGEN2034+AGEN1884 (Cohort 2). Patients from
      Cohort 1 who experience PD may be considered (as PD-1 resistant) for transition to Cohort 2.

      In Part 2, the study will enroll checkpoint inhibitor naïve patients for treatment with
      combination AGEN2034+AGEN1884 (Cohort 3). Part 2 will begin enrollment after enrollment in
      Part 1 is completed.

      All patients will receive study treatment for up to 2 years until confirmed disease
      progression, unacceptable toxicity, or until the patient wishes to withdraw consent for any
      reason. Patients will be followed for safety at 30 and 90 days, and for survival every 2
      months for at least 12 months from their last dose of study treatment. Each treatment cycle
      will be 6 weeks.

      An IRC will be established to adjudicate tumor response based on imaging studies,
      photography, and clinical response. The primary endpoints will be based on the IRC assessment
      of response per RECIST v1.1.
    

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimentalAGEN2034 - dose of 3 mg/kg IV every 2 weeks for up to 24 months
  • AGEN2034
Combination TherapyExperimentalAGEN2034 - dose of 3 mg/kg IV every 2 weeks + AGEN1884 - dose of 1 mg/kg IV every 6 weeks (following AGEN2034 infusion), for up to 24 months
  • AGEN2034
  • AGEN1884

Eligibility Criteria

        Inclusion Criteria

        To be eligible for this study, patients must meet the following inclusion criteria:

          1. Histologically confirmed AS not amenable to curative intent surgery

          2. Prior treatment history for AS

               1. Cohort 1 and Cohort 3

                    -  Patients who previously received and progressed after at least 1 prior
                       therapy for AS.

                    -  Checkpoint inhibitor (PD-1/PD-L1/CTLA-4) naïve

               2. Cohort 2

                    -  Patients who previously received and progressed on or after at least 1 prior
                       therapy for AS

                    -  Prior treatment must include PD-1 or PD-L1 inhibitor such as nivolumab,
                       pembrolizumab, atezolizumab, durvalumab, AGEN2034, or other, given either as
                       the most recent treatment or earlier. Note: Confirmation of PD is required
                       after treatment with prior checkpoint inhibitors

                    -  CTLA-4 inhibitor naïve

          3. ≥ 18 years of age.

          4. At least one lesion measurable, either radiologically (computed tomography [CT],
             magnetic resonance imaging [MRI]) and/or using color photography with a ruler, as per
             RECIST v1.1

          5. Have a life expectancy of ≥ 3 months and an Eastern Cooperative Oncology Group
             Performance Status of 0 to 1

          6. Resolution of all acute AEs resulting from prior cancer therapies to National Cancer
             Institute Common Terminology Criteria for Adverse Events Version 5.0 Grade ≤ 1

          7. Have adequate organ function as indicated by the following laboratory values:

               1. Adequate hematological function defined by absolute neutrophil count > 1.5 ×
                  10^9/L, platelet count > 75 × 10^9/L, and hemoglobin > 8 g/dL (without
                  transfusions, within

                  1 week of first dose)

               2. Adequate hepatic function based by a total bilirubin level ≤ × 1.5 the upper
                  limit of normal (ULN), aspartate aminotransferase level ≤ 2.5 × ULN, alanine
                  aminotransferase level ≤ 2.5 × ULN, alkaline phosphatase ≤ 2.5 × ULN, and albumin

                  ≥ 3.0 mg/dL

               3. 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

               4. Adequate coagulation defined by international normalized ratio or prothrombin
                  time ≤ 1.5 × ULN (unless the patient is receiving anticoagulant therapy); and
                  activated partial thromboplastin time ≤ 1.5 × ULN (unless the patient is
                  receiving anticoagulant therapy)

          8. Willing to undergo mandatory fresh tumor biopsy, from a site not previously irradiated
             (unless progressed after radiation treatment) Note: Tissue from core, or punch
             excisional biopsy, or from resection is required

          9. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test at
             Screening (within 72 hours prior to first dose of study medication)

             Note: 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/or oophorectomy and
                  follicle-stimulating hormone value in the postmenopausal range upon pre-study
                  (Screening) evaluation

               3. Status is post hysterectomy, oophorectomy, or tubal ligation

         10. WCBP must be willing to use highly effective contraception throughout the study,
             starting with the Screening Visit through 90 days after the last dose of study
             treatment

         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

         12. Willingness and ability to consent to participate in study and comply with all study
             procedures

        Exclusion Criteria

        To be eligible for this study, patients must not have any of the following exclusion
        criteria:

          1. Is currently participating and receiving study therapy or has participated in a
             different study of an investigational agent and received study therapy or used an
             investigation device within 3 weeks of the first dose of treatment

          2. Has an inadequate washout period prior to first dose of study drug defined as:

               1. < 3 weeks from last dose of prior systemic cytotoxic chemotherapy or biological
                  therapy

               2. < 3 weeks from last radiation therapy

               3. < 4 weeks from major surgery

          3. Known severe (Grade ≥ 3) hypersensitivity reactions to fully human mAbs, antibody, or
             severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring
             treatment with steroids

          4. Has received 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 intravenous (IV) contrast allergies/reactions is allowed). Patients
             who are receiving daily corticosteroid replacement therapy are an exception to this
             rule. Daily prednisone at doses of up to 7.5 mg or equivalent hydrocortisone dose are
             examples of permitted replacement therapy

          5. Known central nervous system 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 (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, high-dose steroids must be discontinued ≥ 7 days prior to first
             dose of study drug but may be continued if ≤ 5 mg/day (prednisone)

          6. Has active or history of autoimmune disease requiring immunosuppressive systemic
             treatment (e.g. modifying agents, corticosteroids or immunosuppressive drugs) within
             previous 2 years Note: Thyroxine, insulin, or physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency is not considered a form of
             immunosuppressive systemic treatment.

             Note: Patients with Type 1 diabetes, vitiligo, psoriasis, hypo-, or hyperthyroid
             disease not requiring immunosuppressive treatment are eligible

          7. Has had an allogeneic tissue/solid organ transplant

          8. Has or had interstitial lung disease or has had a history of pneumonitis anaphylaxis,
             or uncontrolled asthma that has required oral or IV corticosteroids

          9. Active infection requiring IV systemic therapy

         10. Known history of HIV type 1 or 2 antibodies

         11. Known active infection with hepatitis B and/or hepatitis C virus

         12. History of seizure disorders

         13. Clinically significant 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

         14. History or current evidence of any condition, therapy, 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

         15. Psychiatric or substance abuse disorder that would interfere with cooperation with the
             requirements of the study

         16. Legally incapacitated or has limited legal capacity

         17. Pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate of single-agent AGEN2034 and combination AGEN2034 + AGEN1884
Time Frame:48 months
Safety Issue:
Description:To evaluate the response rate of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with recurrent angiosarcoma

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Agenus Inc.

Last Updated

October 22, 2020