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

NCT05033132 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: C-750-CN01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 43

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.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

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

  36 months

Secondary Outcomes (18)

• ORR Of Balstilimab Monotherapy Per Investigator Assessment Based Upon RECIST 1.1

  36 months

• Disease Control Rate (DCR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1

  36 months

• Duration of Response (DOR) 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

• Progression-free Survival (PFS) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1

  36 months

Study Arms (2)

Balstilimab

EXPERIMENTAL

Balstilimab monotherapy: approximately 147 patients.

Drug: Balstilimab

Balstilimab + Zalifrelimab

EXPERIMENTAL

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

Drug: Balstilimab + Zalifrelimab

Interventions

Balstilimab DRUG

Anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody

Balstilimab

Balstilimab + Zalifrelimab DRUG

An anti-PD-1 monoclonal antibody in combination with a cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody

Balstilimab + Zalifrelimab

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female only
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate by giving written informed consent.
• Diagnosis:
• 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 1.1. 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.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Have satisfactory organ function as indicated by the following laboratory values:
• Bone marrow: absolute neutrophil count \>1.5 × 10\^9/liter (L), platelet count \>100 × 10\^9/L, and hemoglobin \>8 grams (g)/deciliter (80 g/deciliter) (without transfusions of blood or blood component within 2 weeks of test);
• Liver: serum total bilirubin (TBIL) level ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) level ≤2.5 × ULN, alanine aminotransferase (ALT) level ≤2.5 × ULN (TBIL ≤1.5 × ULN, AST ≤5 × ULN, ALT ≤5 × ULN in case of presence of liver metastases);
• Serum creatinine ≤1.5 × ULN; or endogenous creatinine clearance ≥50 milliliters/minute for serum creatinine \>1.5 × ULN;
• Eligible coagulation function, defined as International Normalized Ratio and prothrombin time ≤1.5 x institutional upper limit of normal (IULN); and activated partial thromboplastin time ≤1.5 x IULN.
• No history of other malignancies within 5 years prior to first dose, except for basal cell carcinoma of the skin, superficial bladder cancer, and squamous cell carcinoma of the skin.

You may not qualify if:

• 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.
• Has had an allogeneic tissue/solid organ transplant.
• History of interstitial lung disease or a history of pneumonia that has required oral or intravenous corticosteroids.
• Symptoms of an active infection requiring intravenous systemic therapy.
• Positive human immunodeficiency virus antibody or positive syphilis spirochete antibody and positive syphilis spirochete antibody titer test result (i.e., active syphilis infection).
• Presence of active hepatitis B, hepatitis C or tuberculosis. Active hepatitis B and C are defined as follows: active hepatitis B, positive for hepatitis B surface antigen with the hepatitis B virus deoxyribonucleic acid quantification result greater than the ULN; active hepatitis C, positive for hepatitis C antibody with the hepatitis C virus ribonucleic acid quantification result greater than the ULN.

Sponsors & Collaborators

• Agenus Inc.: lead
• Betta Pharmaceuticals Co., Ltd.: collaborator

Study Sites (43)

Betta Clinical Study Site 4

Bengbu, Anhui, 233004, China

Location

Betta Clinical Study Site 2

Hefei, Anhui, 230036, China

Location

Betta Clinical Study Site 3

Hefei, Anhui, 230601, China

Location

Betta Clinical Study Site 27

Wuhu, Anhui, 241001, China

Location

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

Location

Betta Clinical Study Site 25

Beijing, Beijing Municipality, 100123, China

Location

Betta Clinical Study Site 42

Chongqing, Chongqing Municipality, 400030, China

Location

Betta Clinical Study Site 9

Fuzhou, Fujian, 350014, China

Location

Betta Clinical Study Site 22

Xiamen, Fujian, 361003, China

Location

Betta Clinical Study Site 41

Lanzhou, Gansu, 730000, China

Location

Betta Clinical Study Site 39

Lanzhou, Gansu, 730099, China

Location

Betta Clinical Study Site 14

Huizhou, Guangdong, 516001, China

Location

Betta Clinical Study Site 18

Meizhou, Guangdong, 514031, China

Location

Betta Clinical Study Site 10

Zhanjiang, Guangdong, 524001, China

Location

Betta Clinical Study Site 11

Nanning, Guangxi, 530021, China

Location

Betta Clinical Study Site 5

Cangzhou, Hebei, 061001, China

Location

Betta Clinical Study Site 40

Harbin, Heilongjiang, 150081, China

Location

Betta Clinical Study Site 43

Wuhan, Hubei, 430014, China

Location

Betta Clinical Study Site 28

Wuhan, Hubei, 430060, China

Location

Betta Clinical Study Site 12

Wuhan, Hubei, 430070, China

Location

Betta Clinical Study Site 29

Wuhan, Hubei, 430071, China

Location

Betta Clinical Study Site 31

Xiangyang, Hubei, 441021, China

Location

Betta Clinical Study Site 6

Changde, Hunan, 415003, China

Location

Betta Clinical Study Site 36

Changsha, Hunan, 410008, China

Location

Betta Clinical Study Site 35

Changsha, Hunan, 410011, China

Location

Betta Clinical Study Site 13

Changsha, Hunan, 410013, China

Location

Betta Clinical Study Site 21

Nanjing, Jiangsu, 210008, China

Location

Betta Clinical Study Site 8

Nanjing, Jiangsu, 210009, China

Location

Betta Clinical Study Site 38

Ganzhou, Jiangxi, 341099, China

Location

Betta Clinical Study Site 19

Nanchang, Jiangxi, 330006, China

Location

Betta Clinical Study Site 20

Nanchang, Jiangxi, 330006, China

Location

Betta Clinical Study Site 24

Shangrao, Jiangxi, 334000, China

Location

Betta Clinical Study Site 16

Changchun, Jilin, 130021, China

Location

Betta Clinical Study Site 15

Changchun, Jilin, 130041, China

Location

Betta Clinical Study Site 7

Dalian, Liaoning, 116021, China

Location

Betta Clinical Study Site 34

Shenyang, Liaoning, 110001, China

Location

Betta Clinical Study Site 17

Shenyang, Liaoning, 110046, China

Location

Betta Clinical Study Site 30

Xi'an, Shaanxi, 710061, China

Location

Betta Clinical Study Site 23

Taiyuan, Shanxi, 030013, China

Location

Betta Clinical Study Site 26

Tianjin, Tianjin Municipality, 300000, China

Location

Betta Clinical Study Site 37

Tianjin, Tianjin Municipality, 300000, China

Location

Betta Clinical Study Site 32

Ürümqi, Xinjiang, 830011, China

Location

Betta Clinical Study Site 33

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 2, 2021
• Study Start: October 1, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

CN (43)