An Open-label, Multicenter Phase II Study Evaluating Balstilimab Alone or Balstilimab in Combination With Zalifrelimab in Patients With Advanced Cervical Cancer

Agenus Inc.43 sites in 1 countryOctober 1, 2021

ConditionsCervical Cancer

InterventionsBalstilimab Balstilimab + Zalifrelimab

DrugsBalstilimab Balstilimab + Zalifrelimab

Overview

Phase: Phase 2
Intervention: Balstilimab
Conditions: Cervical Cancer
Sponsor: Agenus Inc.
Locations: 43
Primary Endpoint: Objective Response Rate (ORR) Of Balstilimab Monotherapy Per Independent Review Committee (IRC) Assessment Based Upon Response Evaluation Criteria In Solid Tumours (RECIST) 1.1
Status: Withdrawn
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multi-center Phase II 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.

Registry

clinicaltrials.gov

Start Date

October 1, 2021

End Date

December 30, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Agenus Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Voluntarily agree to participate by giving written informed consent.
•Diagnosis:
•Have a histologically or cytologically confirmed, locally advanced, inoperable and/or metastatic cervical squamous cell carcinoma, cervical adenosquamous cell carcinoma or cervical adenocarcinoma. Note: A pathological report confirmed by histology or cytology of the primary tumor is required for definitive diagnosis. The following cervical tumors are not eligible for inclusion: minimal deviation adenocarcinoma, gastric-type endocervical adenocarcinoma, clear cell adenocarcinoma of the cervix, neuroendocrine carcinoma of the cervix and mesonephric adenocarcinoma.
•Patients with recurrent/metastatic cervical cancer who have received at least 1 platinum-based systemic therapy (excluding radiosensitizing chemotherapy) (with or without bevacizumab), and experienced recurrence or progression of cervical cancer or were intolerable to chemotherapy toxicity during or after the systemic therapy and were unable to receive radiotherapy or radical surgery again. Note (definition of failure or intolerability of first-line platinum-based chemotherapy):
•Patients with recurrent or metastatic cervical cancer who have experienced disease progression during platinum-based regimen or have experienced disease progression after receiving ≥4 cycles of effective platinum-based regimen (complete response/progressive disease/stable disease) or were intolerable to toxicity caused by platinum during/after platinum-based regimen and were not suitable for continuous platinum-based regimen.
•Patients with cervical cancer progressed or relapsed during neoadjuvant or adjuvant chemotherapy with platinum-based regimen (≥4 cycles if the platinum-based regimen is effective) or within 6 months after the end of the treatment, are deemed to have failed first-line platinum-based chemotherapy.
•Programmed death-ligand 1 (PD-L1) positive (combined positive score ≥1).
•Have at least 1 measurable lesion on imaging based on RECIST 1.
•Measurable lesions should have not been treated with topical treatment such as radiotherapy. If the only one measurable lesion has been treated with previous topical treatment (radiotherapy, ablation, vascular intervention, etc.), it is necessary to confirm that the lesion has progressed, otherwise it will be recorded as a non-target lesion.
•Have a life expectancy of at least 3 months.

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: received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose; received radiation therapy within 3 weeks before first dose; experienced major surgical procedures within 4 weeks prior to the first dose.
•Has received prior therapy with any antibody/drug-targeting T-cell co-stimulatory proteins (immune checkpoints), including but not limited to PD-1, PD-L1, CTLA-4, lymphocyte-activation gene 3, therapeutic vaccines, etc.
•Have not recovered from the toxicity of their last systemic antineoplastic therapy to grade 1 or below as defined by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0 prior to the first dose of the study. Note: Patients with sensory neuropathy or alopecia grade ≤2 are eligible.
•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 5.0 Grade ≥3).
•Received hematopoietic stimulating factor treatment within 14 days (≤14 days) before the first dose of the study drug, such as granulocyte colony-stimulating factor, erythropoietin, etc.
•Central nervous system tumors, brain metastases, or meningeal metastases are found prior to the first dose of the study drug. Note: Patients with brain metastases are eligible for the study when meeting the following requirements: brain metastases prove to be stable (patients are required to provide the most recent head imaging prior to the first dose, with previous head imaging at least 4 weeks apart, for the investigator to determine whether the brain metastases are stable by comparing the results of the two examinations); any neurological symptoms resulting from brain metastases or their treatment must have resolved or be maintainable to a minimal degree and the symptoms can be clinically determined to be sequelae of the treated lesion; brain metastases treated with steroids must not be treated with steroids for at least 4 weeks prior to the first dose.
•Treatment with systemic corticosteroids or any other form of systemic immunosuppression within 7 days (≤7 days) prior to the first dose of the study drug. Note: Combination with corticosteroids for the treatment of immune-related adverse events and prophylactic use of anticontras allergy medications are permitted during the study period; patients requiring daily corticosteroid replacement therapy, e.g., 5 to 7.5 milligrams daily doses of prednisone or equivalent doses of hydrocortisone and steroid therapy (topical, intraocular, intranasal inhalation routes only) may be enrolled in this study. Note: Patients with type 1diabetes, vitiligo, psoriasis, hypothyroidism, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
•Active autoimmune disease requiring systemic therapy within the past 2 years or history of autoimmune disease or syndrome requiring systemic steroids/immunosuppressive drugs, e.g., hypophysitis, colitis, hepatitis, nephritis, etc. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for renal or pituitary insufficiency) is not considered systemic immunosuppressive therapy. Note: Patients with type I diabetes, vitiligo, psoriasis, hypo- or hyperthyroidism who do not require immunosuppressive therapy are eligible for the study.

Arms & Interventions

Balstilimab

Balstilimab monotherapy: approximately 147 patients.

Intervention: Balstilimab

Balstilimab + Zalifrelimab

Balstilimab in combination with Zalifrelimab (combination therapy): approximately 30 patients.

Intervention: Balstilimab + Zalifrelimab

Outcomes

Primary Outcomes

Objective Response Rate (ORR) Of Balstilimab Monotherapy Per Independent Review Committee (IRC) Assessment Based Upon Response Evaluation Criteria In Solid Tumours (RECIST) 1.1

Time Frame: 36 months

Secondary Outcomes

Duration of Response (DOR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
Area Under The Plasma Concentration Versus Time Curve From The Time Of Administration To The Last Measurable Concentration (AUC0-t) Of Balstilimab And Zalifrelimab(Pre-dose (2 hours prior to dosing [dosing to occur every 6 weeks for up to 24 months/17 cycles or until continued disease progression or intolerable toxicity]), End of Treatment)
Disease Control Rate (DCR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
Time to Response (TTR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
Overall Survival (OS) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1(48 months)
Peak Plasma Concentration (Cmax) Of Balstilimab And Zalifrelimab(Pre-dose (2 hours prior to dosing [dosing to occur every 6 weeks for up to 24 months/17 cycles or until continued disease progression or intolerable toxicity]), End of Treatment)
Time To Peak Plasma Concentration (Tmax) Of Balstilimab And Zalifrelimab(Pre-dose (2 hours prior to dosing [dosing to occur every 6 weeks for up to 24 months/17 cycles or until continued disease progression or intolerable toxicity]), End of Treatment)
ORR Of Balstilimab Monotherapy Per Investigator Assessment Based Upon RECIST 1.1(36 months)
TTR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
PFS Of Combined Therapy Of Balstilimab and Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
Progression-free Survival (PFS) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
ORR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
DCR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
DOR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(36 months)
OS Of Combined Therapy of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1(48 months)
Half-life (T1/2) Of Balstilimab And Zalifrelimab(Pre-dose (2 hours prior to dosing [dosing to occur every 6 weeks for up to 24 months/17 cycles or until continued disease progression or intolerable toxicity]), End of Treatment)
Number Of Participants With Anti-drug Antibodies For Balstilimab And Zalifrelimab(36 months)
Number Of Participants With Treatment-emergent Adverse Events(48 months)