A Phase 2 Study of Balstilimab Independently or in Combination With Zalifrelimab in Cervical Cancer

• Status: Recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is a randomized, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy ,safety and pharmacokinetics of Balstilimab (Treatment Arm 1 - monotherapy) or in combination with Zalifrelimab (Treatment Arm 2- combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Agenus Inc.
• Collaborator: Betta Pharmaceuticals Co., Ltd.

Criteria

Inclusion Criteria:

• Voluntarily agree to participate by giving written informed consent.

• Be ≥18 years of age.

• Diagnosis:

1. Have a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and metastatic, locally advanced, and/or unresectable disease at the time of enrollment.

Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma.

2. Has cervical cancer and has relapsed after a platinum based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease;

3. PD-L1 positive(CPS≥1).

• Have measurable disease on imaging based on RECIST version 1.1.

• Have a life expectancy of at least 3 months.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

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

1. Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5 x 10^9/L, platelet count > 100 x 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 institutional upper limit of normal (ULN), aspartate aminotransferase (AST) level ≤ 2.5 x ULN, alanine aminotransferase (ALT) level ≤ 2.5 x ULN, and alkaline phosphatase ≤ 2.5 x ULN.

3. Adequate renal function defined as creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured and calculated creatinine clearance ≥50 mL/minute per Institutional standard.

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

• Has no history of another primary malignancy with no known active disease ≥5 years before the first dose of study drug, with the exception of adequately treated non-melanoma skin cancer , lentigo maligna or superficial bladder cancer.

• Patients must provide a sufficient and adequate FFPE tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of advanced or metastatic disease has been made AND from a site not previously irradiated. If no tumor tissue is available, a fresh biopsy will be required.

• Patients must have a negative serum pregnancy test at screening (within 7 days of first dose of study medication) if of childbearing potential or be of non-child bearing potential. Non-childbearing potential is defined as (by other than medical reasons):

1. ≥45 years of age and has not had menses for greater than 1 year,

2. Amenorrheic ≥ 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation,

3. History of hysterectomy, oophorectomy or tubal ligation.

• If of childbearing potential, female patients must be willing to use adequate barrier methods throughout the study, starting with the screening visit through 12 months after the last dose of study treatment.

• Is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

• Is 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 4 weeks of the first dose of treatment.

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

1. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose, or,

2. Received radiation therapy within 3 weeks before first dose, or,

3. Had major surgery within 4 weeks before first dose.

• Has received prior therapy with Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies or Lag3.

• Is 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).

• Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Grade ≥3).

• Received hematopoietic stimulating factor treatment within 7 days (≤ 7 days) before the first dose, such as granulocyte colony stimulating factor (G-CSF), erythropoietin, etc.

• Has a central nervous system (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 (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, steroids must be discontinued ≥ 7 days prior to first dose of study drug.

-Has active or history of autoimmune disease that has required immunosuppressive systemic treatment within 2 years of the start of trial treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of immunosuppressive systemic treatment.

Note: Patients with diabetes type 1, vitiligo, psoriasis, hypothyroidism, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

• Has had an allogeneic tissue/solid organ transplant.

• Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or intravenous corticosteroids.

• Has an active infection requiring intravenous systemic therapy.

• Has known history of Human Immunodeficiency Virus (HIV) or treponema pallidum.

• Has known active Hepatitis B (HBV), Hepatitis C (HCV), or tuberculosis.Active Hepatitis B is defined as a known positive HBsAg or HBcAb result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.

• Has 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, cerebrovascular accident, transient ischemic attack, cerebral embolism.

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

• Has known psychiatric that would interfere with cooperation with the requirements of the trial.

• Has a history of substance abuse, alcoholism or other addictions.

• Is legally incapacitated or has limited legal capacity.