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Advanced CancerPhase 3NCT04943627

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

A Phase 3 study testing Balstilimab (BAL), Topotecan and Vinorelbine in people with Advanced Cancer and Metastatic Cervical Cancer, run by Agenus Inc. at 3 sites in 2 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Advanced Cancer, Metastatic Cervical Cancer
What is being tested?
Balstilimab (BAL), Topotecan and Vinorelbine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesin 2 countries
Study dates
2 Aug 2021to 22 Oct 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Measurable disease - based on Investigator assessment.
  • 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).
  • Normal thyroid function (thyroid stimulating hormone) whether or not the patient is on supplemental thyroid hormone.
  • Has no history of another primary malignancy except:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug and of low potential risk for recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • Women of childbearing potential (WOCP) must have a negative serum pregnancy test at Screening (within 72 hours before first dose of study drug). Non-childbearing potential is defined as (by other than medical reasons):
  • ≥ 45 years of age and has not menstruated for greater than 1 year.
  • Definitive pelvic radiation for the treatment of cervical cancer.
  • Whose status is post hysterectomy, bilateral oophorectomy, or tubal ligation.
  • WOCP must be willing to use 2 highly effective methods of contraception (defined in the informed consent form) throughout the trial, starting with the Screening Visit through 90 days after the last dose of study drug Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • Is willing and able to comply with the requirements of the protocol.

Who cannot join

  • 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:
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  • 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.
  • Has active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study drug (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) Note: Patients with autoimmune conditions requiring hormone replacement therapy or topical treatments are eligible.
  • Has had an allogeneic tissue/solid organ transplant requiring ongoing immunosuppressive treatment.
  • Has or had known drug-induced interstitial lung disease, not fully resolved, or has had a history of pneumonitis that has required oral or IV corticosteroids.
  • Has an active infection requiring IV systemic treatment.
  • Has known history of HIV (HIV 1/2 antibodies).
  • Has known untreated hepatitis B/hepatitis C virus (HBV/HCV) or tuberculosis. Active HBV is defined as a known positive hepatitis B surface antigen result. Active HCV is defined as a known positive hepatitis C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
  • Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months before enrollment, unstable angina, congestive heart failure (New York Heart Association Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
  • Has other systemic conditions or organ abnormalities that in the opinion of the Investigator may interfere with the conduct and/or interpretation of the current trial.
  • Has known psychiatric or substance use disorders that would interfere with cooperation or compromise participation with the requirements of the trial.
  • Is legally incapacitated or has limited legal capacity.
  • Is pregnant or breastfeeding.
  • Has received a live/attenuated vaccine within 14 days of first dose of study treatment and other vaccines within 48 hours of first dose of study treatment.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Armenia2 sites

  • Hematology Center after prof. R. Yeolyan

    Yerevan, 0014

  • National Center of Oncology named after V.A. Fanarjian

    Yerevan, 0052

Other trials in Armenia

United States1 site

  • Optimum Research (Southwest Women's Oncology Center)

    Albuquerque, New Mexico, 87109

Other trials in United States

About this study

Official title: A Phase 3 Trial of Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer After Platinum-Based Chemotherapy (BRAVA)

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.

Read the detailed description

The purpose of this Phase 3 trial is to demonstrate prolongation of OS in patients treated with BAL as compared to IC chemotherapy.

This Phase 3 trial is an open-label, randomized study with single-agent BAL or 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.

Population:

Patients with recurrent, unresectable, or metastatic cervical cancer who have progressed after receiving at least 1 prior line of platinum-containing chemotherapy with or without bevacizumab.

In this study, > 50% of patients will have received prior treatment with bevacizumab, which will be determined prior to enrollment.

Stratification

  • Histology (squamous cell carcinoma [SCC] vs adenocarcinoma [AC] or adenosquamous carcinoma [ASC])
  • Region of the world (United States or Europe Union or Australia vs other countries)
  • Eastern Cooperative Oncology Group (ECOG) status 0 vs 1

Randomization

  • 2:1, BAL: IC chemotherapy

Approximately 486 patients will be enrolled and randomized with 2:1 allocation between the BAL and IC chemotherapy arms.

Being tested
Balstilimab (BAL), Topotecan, Vinorelbine, Gemcitabine, Irinotecan
Keywords
Advanced Cancer, Metastatic Cervical Cancer, Open-Label, Randomized, Monotherapy, Anti-PD-1
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04943627
Study groupRoleWhat they receive
Monotherapy with Balstilimab (BAL)Experimental300 mg IV once every 3 weeks for up to 24 months
Receives: Drug: Balstilimab (BAL)
Monotherapy with Investigator Choice (IC) Chemotherapy per Institutional guidelinesActive comparatorTopotecan: 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
Receives: Drug: Topotecan; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Irinotecan; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

Secondary outcomes (4)

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

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

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

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

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

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

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

    Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients with PD-L1 positive tumors randomized to BAL and to IC chemotherapy.

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

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

    Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients randomized to BAL and to IC chemotherapy.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2021
  2. Study start2 Aug 2021
  3. Primary completion22 Oct 2021
  4. Study completion22 Oct 2021

Why it stopped: Strategic Business Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04943627
Sponsor's protocol ID
C-700-03
Status last verified
Oct 2022
First submitted
4 Jun 2021
Last updated
5 Oct 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Balstilimab (BAL), Topotecan and Vinorelbine in people with Advanced Cancer and Metastatic Cervical Cancer, run by Agenus Inc. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Armenia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy (time frame: time until observing 234 OS events but no later than 36 months after enrollment of the last patient). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04943627.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2022.

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