A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma

A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma

Inclusion Criteria:

  • Diagnosis of recurrent, unresectable, or metastatic DDLPS

    • The definition of recurrent disease is a patient with a primary tumor that has been successfully resected, but has recurred after primary surgery
    • Any number of prior systemic therapies will be allowed
  • Age ≥ 18 years at the time of informed consent
  • Willing and able to provide written informed consent/assent for the trial
  • Willing to comply with treatment protocol
  • Adequate performance status: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1/Karnofsky Performance Status (KPS) 70-100%
  • Presence of measurable disease per RECIST v1.1

    o Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression

  • QTc ≤ 480 msec using Fredericia’s QT correction formula
  • Adequate organ function determined within 2 weeks of treatment initiation, defined as follows:

    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count ≥ 1,500/mm3 (1.0 x 109/L)
    • Platelet count ≥ 75,000/mm3 (50 x 109/L)
    • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for a patient with total bilirubin level > 1.5 x ULN
    • Aspartate aminotransferase (AST) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases
    • Alkaline phosphatase < 5 x ULN
    • Serum creatinine ≤ 1.5 x ULN or a measured or calculated creatinine clearancea

      ≥ 60 mL/min for a patient with creatinine levels > 1.5 x institutional ULN (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. GFR can also be used in place of creatinine or CrCl)

    • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    • Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants
  • For female patients of childbearing potential, negative serum pregnancy test at screening visit and within 72 h prior to the first dose of study medication

aCreatinine clearance should be calculated per institutional standard.

Contraception Requirements

Female participants of reproductive potential and male participants with female partners of reproductive potential are required to use highly effective contraceptive measures from the first dose of study treatment until 30 days after the last dose of etrumadenant or 90 days after the last dose of zimberelimab, whichever is longer.

Highly effective contraception is defined as use of one or more methods that result in a low failure rate (i.e., less than 1%). Highly effective contraceptive measures include:

  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
  • Progestogen only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
  • Intrauterine device
  • Intrauterine hormone-releasing system in combination with a barrier method (preferably male condom)
  • Surgical sterilization

    • Female participant or female partner of the male participant has undergone bilateral tubal ligation
    • Male participant is vasectomized (with documented medical confirmation of surgical success) and is the sole sexual partner of a female with reproductive potential
  • Complete sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant

To ensure proper birth control, female participants who use hormonal contraception should use an efficient barrier contraceptive (condom plus spermicide). Additionally, male participants, when having sexual intercourse with a female of reproductive potential, should use an efficient barrier contraceptive (condom plus spermicide); the respective partner should also use an additional efficient contraceptive method (e.g., oral pills, intrauterine device, or diaphragm, and spermicide).

Exclusion Criteria:

Patients who fulfil any of the following criteria are not eligible for admission to the study:

  • Prior treatment with systemic PD-1 or PD-L1 inhibitor
  • Prior treatment with an agent targeting the adenosine pathway
  • Have a concurrent unrelated malignancy that requires active treatment

    o Patients with concurrent malignancies of a different tumor whose natural history or treatment will likely not interfere with the safety or efficacy assessment of the investigational drug will be eligible

  • Uncontrolled intercurrent illness including active infection requiring systemic therapy or symptomatic congestive heart failure within the past 6 months
  • Has known active central nervous system (CNS) metastases

    • Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study Day 1 and return to baseline of neurologic symptoms), and have no evidence of new or enlarging brain metastases. This exception does not include sarcomatous meningitis, which is excluded regardless of clinical stability.
    • Patients must be on a stable or decreasing corticosteroid dose at the time of study entry; patients who require escalating doses of corticosteroids for the treatment of CNS metastases will be excluded.
  • Shows evidence of clinically significant immunosuppression such as the following:

    • Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
    • Concurrent opportunistic infection
    • Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to enrollment. However, in the setting of non-immune mediated indications for use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator.
  • Has a known infection with HIV AND

    • CD4+ T-cell (CD4+) counts < 350 cells/uL
    • An opportunistic infection within the prior 12 months
  • Has a known active infection with hepatitis B or hepatitis C

    • Chronic carriers of HBV infection (HBsAg-positive, undetectable or low HBV DNA, and normal ALT) or individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive) may be eligible if suppressive antiviral therapy can be safely administered.
    • Patients who have completed curative antiviral treatment for HCV and have a viral load below the limit of quantification will be eligible (e.g. a patient who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution)
  • Has a known history of active tuberculosis infection
  • Has history or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in the past 2 years.

Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.

Source: View full study details on ClinicalTrials.gov

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June 4, 2023Comments OffClinicalTrials.gov | Oncology Clinical Trials | Oncology Studies | US National Library of Medicine