Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA)

NCT04943627 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: C-700-03
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

Brief Summary

This Phase 3 trial is an open-label, randomized study with single-agent Balstilimab (BAL) or Investigator Choice (IC) chemotherapy (single-agent gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan) in patients with recurrent, persistent, or metastatic cervical cancer who have progressed after receiving platinum based chemotherapy.

Conditions

Advanced Cancer; Metastatic Cervical Cancer

Keywords

Advanced Cancer; Metastatic Cervical Cancer; Open-Label; Randomized; Monotherapy; Anti-PD-1

Outcome Measures

Primary Outcomes (2)

• Overall survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy

  Hazard Ratio for Overall Survival (OS) by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients with PD-L1 positive tumors

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Overall survival in all patients randomized to BAL vs Investigator's Choice chemotherapy

  Hazard Ratio for OS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

Secondary Outcomes (4)

• Progression-free survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Progression-free survival in all patients randomized to BAL vs Investigator's Choice chemotherapy

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Objective response rate (ORR) to BAL and to IC chemotherapy in patients with PD-L1 positive tumors

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Objective response rate (ORR) to BAL and to IC chemotherapy in all patients' tumors

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

Other Outcomes (9)

• Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

• Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

  time until observing 234 OS events but no later than 36 months after enrollment of the last patient

Study Arms (2)

Monotherapy with Balstilimab (BAL)

EXPERIMENTAL

300 mg IV once every 3 weeks for up to 24 months

Drug: Balstilimab (BAL)

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

ACTIVE COMPARATOR

Topotecan: 1 or 1.25 mg/m\^2 IV on Days 1 to 5, every 21 days or Vinorelbine: 30 mg/m\^2 IV on Days 1 and 8, every 21 days or Gemcitabine: 1000 mg/m\^2 IV on Days 1 and 8, every 21 days or Irinotecan: 100 or 125 mg/m\^2 IV weekly for 28 days, every 42 days or Pemetrexed: 500 mg/m\^2 IV on Day 1, every 21 days

Drug: Topotecan; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Irinotecan; Drug: Pemetrexed

Interventions

Balstilimab (BAL) DRUG

Anti-PD-1 Monoclonal antibody

Also known as: AGEN2034, Anti-PD-1

Monotherapy with Balstilimab (BAL)

Topotecan DRUG

Chemotherapy

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

Vinorelbine DRUG

Chemotherapy

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

Gemcitabine DRUG

Chemotherapy

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

Irinotecan DRUG

Chemotherapy

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

Pemetrexed DRUG

Chemotherapy

Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelines

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate by giving written informed consent.
• ≥ 18 years of age.
• Diagnosis and prior systemic treatment:
• Has recurrent or metastatic cervical cancer (SCC, AC, or ASC histology) and has experienced disease progression during or after treatment with a standard platinum based therapy with or without bevacizumab.
• Has received at least 1 prior systemic therapy regimen for recurrent, persistent, and/or metastatic cervical cancer.
• Note: Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a prior systemic therapy regimen for recurrent, persistent, and/or metastatic cervical cancer.
• Measurable disease - based on Investigator assessment.
• a. Radiological evidence of measurable disease on imaging based on RECIST v1.1 Note: Patients must have at least 1 "target lesion" to be used to assess response, as defined by RECIST v1.1. Tumors within a previously irradiated field will be designated as "non target" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Has a life expectancy of at least 3 months and an ECOG performance status of 0 or 1.
• Patients must have sufficient and adequate formalin-fixed tumor tissue sample available that is not older than 3 years; otherwise, a fresh biopsy is required. Archival tissue or fresh biopsy must be from a site not previously irradiated.
• Has adequate organ function as indicated by the following laboratory values:
• Adequate hematological function defined by absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and stable hemoglobin ≥ 8 g/dL (without transfusions within 1 week before first dose).
• Adequate hepatic function based by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN), aspartate aminotransferase (AST) level ≤ 2.5 × ULN, alanine aminotransferase (ALT) level ≤ 2.5 × ULN, alkaline phosphatase (ALP) ≤ 2.5 × ULN, and albumin ≥ 3.0 mg/dL. In the case of hepatic metastases, \< 5 × ULN for AST/ALT and ALP.
• Adequate renal function defined as calculated creatinine clearance \> 40 mL/min or a serum creatinine \< 1.5 × ULN, per institutional standards (creatinine clearance should be calculated per institutional standards).
• Adequate coagulation defined by international normalized ratio or prothrombin time ≤ 1.5 × institutional upper limit of normal IULN unless the patient is receiving anticoagulant therapy) and activated partial thromboplastin time ≤ 1.5 × IULN (unless the patient is receiving anticoagulant therapy).

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a trial of an investigational agent and received study therapy or used an investigational device within 4 weeks before the first dose of treatment.
• Has an inadequate period of time prior to first dose of study treatment that is defined as:
• Received systemic cytotoxic chemotherapy or biological therapy within 28 days before initiation of study treatment
• Received radiation therapy within 28 days before initiation of study treatment, except for palliative bone therapy, which can be received 2 weeks prior to initiation of study treatment
• Had major surgery within 4 weeks before initiation of study treatment
• Has received prior therapy with:
• a. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-programmed cell death protein 1 and anti-PD-L1 antibodies.
• Has persisting toxicity related to prior therapy of NCI-CTCAE v5.0 Grade ≥ 1 severity, with the exceptions noted below:
• Peripheral neuropathy Grade ≤ 2.
• Alopecia Grade ≤ 2.
• 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 v5.0 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma.
• Is receiving systemic corticosteroids ≤ 7 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on trial for management of immune-related adverse events and/or as a premedication for intravenous \[IV\] contrast allergies/reactions is allowed). Patients who are receiving daily corticosteroid replacement therapy are an exception to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5 mg or equivalent hydrocortisone dose and steroid therapy administered by topical, intraocular, intranasal, and/or inhalation routes.
• History of 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 a 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 the first dose of study drug.

Sponsors & Collaborators

• Agenus Inc.: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator

Study Sites (3)

Optimum Research (Southwest Women's Oncology Center)

Albuquerque, New Mexico, 87109, United States

Location

Hematology Center after prof. R. Yeolyan

Yerevan, 0014, Armenia

Location

National Center of Oncology named after V.A. Fanarjian

Yerevan, 0052, Armenia

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

balstilimab; spartalizumab; Topotecan; Vinorelbine; Gemcitabine; Irinotecan; Pemetrexed

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: June 29, 2021
• Study Start: August 2, 2021
• Primary Completion: October 22, 2021
• Study Completion: October 22, 2021
• Last Updated: October 5, 2022

Record last verified: 2022-10

Locations

AR (2); US (1)