Clinical Trials /

A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer

NCT04349280

Description:

The purpose of this study is to evaluate bintrafusp alfa in participants with metastatic or locally advanced urothelial cancer. This trial provides the first evaluation of bintrafusp alfa in participants with urothelial cancer that has progressed following platinum therapy

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer
  • Official Title: A Phase Ib Trial to Evaluate the Efficacy and Safety of Bintrafusp Alfa Monotherapy in Metastatic or Locally Advanced/Unresectable Urothelial Cancer With Disease Progression or Recurrence Following Treatment With a Platinum Agent

Clinical Trial IDs

  • ORG STUDY ID: 213152
  • NCT ID: NCT04349280

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
Bintrafusp alfaParticipants receiving bintrafusp alfa

Purpose

The purpose of this study is to evaluate bintrafusp alfa in participants with metastatic or locally advanced urothelial cancer. This trial provides the first evaluation of bintrafusp alfa in participants with urothelial cancer that has progressed following platinum therapy

Trial Arms

NameTypeDescriptionInterventions
Participants receiving bintrafusp alfaExperimentalParticipants will receive bintrafusp alfa 1200 milligram (mg), intravenous (IV) infusion, once every 2 weeks (Q2W) until progressive disease (PD), death, unacceptable toxicity, study withdrawal or up to 2 years.
  • Bintrafusp alfa

Eligibility Criteria

        Inclusion Criteria:

          -  Participants can give signed informed consent/assent which includes compliance with
             the requirements and restrictions listed in the informed consent form (ICF).

          -  At least eighteen years of age at the time of signing the informed consent.

          -  Participants with histologically confirmed locally advanced or metastatic or locally
             advanced/unresectable urothelial carcinoma (including renal, pelvis, ureter, urinary
             bladder, urethra). Mixed histologies are acceptable provided transitional cell
             carcinoma is the predominant histology. 1. Measurable disease per RECIST v 1.1
             criteria; and 2. Experienced PD or recurrence either following platinum containing
             chemotherapy for metastatic or locally advanced/unresectable urothelial cancer or
             within 12 months from completion of neo-adjuvant or adjuvant platinum-containing
             chemotherapy for localized muscle-invasive urothelial cancer.

          -  Able to provide, a tumor tissue sample collected during screening and prior to
             administration of bintrafusp alfa.

          -  Able to provide an archival tumor sample (preferably from the most recent biopsy).
             Archival material is formalin fixed tumor tissue sample from a biopsy of a tumor
             lesion.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

          -  Participants with adequate organ system functions as defined follows: Absolute
             neutrophil count (ANC) >=1.5*10^9 cells per liter (cells/L); Hemoglobin >=9.0 grams
             per deciliter (g/dL); Platelets >=100*10^9 cells/L; international normalized ratio
             (INR) or prothrombin time (PT) <=1.5*Upper limit of normal (ULN); Albumin >=2.5 g/dL;
             Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <=2.5*ULN or
             <=5*ULN for participants with documented liver metastases; Total bilirubin <=1.5*ULN
             (Isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35 percent); calculated creatinine clearance (CrCI) >=30 milliliter per
             minute (mL/min) and Ejection Fraction >=50 percent.

          -  Life expectancy of at least 12 weeks.

          -  A female is eligible if she is not pregnant or breastfeeding, and at least one of the
             following conditions applies: Not a woman of childbearing potential (WOCBP) or If a
             WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of <1%
             per year), preferably with low user dependency, for the following time periods: Before
             the first dose of the study interventions, if using hormonal contraception: has
             completed at least one 4-week cycle of an oral contraception pill and either had or
             has begun her menses or has used a depot contraceptive or extended-cycle oral
             contraceptive for least 28 days and has a documented negative pregnancy test using a
             highly sensitive assay; during the intervention period; and after the study
             intervention period (i.e., after the last dose of study intervention is administered)
             for at least 2 months.

          -  The Investigator evaluates the effectiveness of the contraceptive method in
             relationship to the first dose of study intervention.

          -  Participant has a negative serum or highly sensitive urine pregnancy test, as required
             by local regulations, within 24 hours before the first dose of study intervention. If
             a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum
             pregnancy test is required.

          -  The Investigator reviews the medical history, menstrual history, and recent sexual
             activity to decrease the risk for inclusion of a female with an early undetected
             pregnancy.

          -  Male participants: Contraceptive use by men should be consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies. Male participants are eligible to participate if they agree to the following
             from the time of first dose of study until 125 days after the last dose of study
             treatment to allow for clearance of any altered sperm: Refrain from donating sperm; Be
             abstinent from heterosexual intercourse as their preferred and usual lifestyle
             (abstinent on long term and persistent basis) and agree to remain abstinent or agree
             to use a male condom and female partner to use an additional highly effective
             contraceptive method with a failure rate of <1% per year when having sexual
             intercourse with a woman of childbearing potential who is not currently pregnant.

          -  Archival tumor sample high for Programmed Death-Ligand 1 (PD-L1) by central assay.

        Exclusion Criteria:

          -  Active brain and/or leptomeningeal disease that is symptomatic or requires therapeutic
             intervention. Participants with asymptomatic central nervous system (CNS) metastases
             who are clinically stable as demonstrated by serial brain images and have no
             requirement for corticosteroids for at least 14 days prior to enrollment are eligible.

          -  History of malignancy other than urothelial cancer within the last 3 years except for
             localized tumors that have been treated with curative intent or have not required
             therapy in the past 2 years. (e.g., resected non-melanoma skin cancer).

          -  No more than 2 lines of systemic therapy for the treatment of metastastic disease. If
             the most recent therapy was not a platinum-based regimen, the participant must have
             progressed on or after that therapy.

          -  Cirrhosis or current unstable liver or biliary disease per investigator assessment
             defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia,
             esophageal or gastric varices, or persistent jaundice.

          -  Current pneumonitis or history of non-infectious pneumonitis that required systemic
             immunosuppressive treatment.

          -  Active autoimmune disease that required systemic immunosuppressive treatment within
             the past 2 years.

          -  Received prior allogeneic/autologous bone marrow or solid organ transplant.

          -  Receiving systemic corticosteroids (>10 mg daily oral prednisone or equivalent) or
             other immunosuppressive agent within 7 days prior to study treatment. Inhaled or
             topical steroids are permitted.

          -  Known severe hypersensitivity reactions to monoclonal antibodies or any ingredient
             used in the study treatment formulation (Grade >=3 NCI-CTCAE v 5.0).

          -  Active infection requiring systemic therapy.

          -  Received any live vaccine within 30 days prior first dose of intervention.

          -  Known history of positive test for human immunodeficiency virus (HIV) with the
             exception of participants with cluster of differentiation 4 (CD4) + T-cell (CD4+)
             counts >=350 cells per microliter (cells /uL) and no history of acquired
             immunodeficiency syndrome (AIDS)-defining opportunistic infections.

          -  Active hepatitis B virus (HBV) (HBV surface antigen-positive).

          -  Active hepatitis C virus (HCV) infection, or positive HCV antibody, with the exception
             of participants that 1. Have HCV viral load below the limits of quantitation and 2.
             Completed curative antiviral therapy or are receiving and compliant with antiviral
             therapy.

          -  History or evidence of cardiac abnormalities within the 6 months prior to first dose
             of intervention which include: a. Serious, uncontrolled cardiac arrhythmia or
             clinically significant electrocardiogram abnormalities including second degree (Type
             II) or third-degree atrioventricular block or QTcF interval >450 millisecond (msec)
             (or QTcF >480 msec for participants with bundle branch block); b. Cardiomyopathy,
             myocardial infarction, acute coronary syndromes (including unstable angina pectoris),
             coronary angioplasty, stenting or bypass grafting; c. Congestive heart failure (Class
             II, III, or IV) as defined by the New York Heart Association functional classification
             system; and d. Symptomatic pericarditis.

          -  Participants with history of bleeding diathesis or recent major bleeding events
             considered by the Investigator as high risk for investigational drug treatment are
             also excluded.

          -  Any other serious or uncontrolled medical disorder that, in the opinion of the
             investigator, may increase the risk associated with study participation or study drug
             administration, impair the ability of the participant to receive protocol therapy, or
             interfere with the interpretation of study results.

          -  Received prior systemic anti-cancer therapy within 2 weeks prior to study treatment.

          -  Received prior therapy with an anti- programmed death 1 (PD-1), anti-PD-L1,
             anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
             antibody (including ipilimumab or any other antibody or drug specifically targeting
             T-cell co-stimulation or checkpoint pathways).

          -  Received prior therapy targeting transforming growth factor (TGF) beta - (e.g.,
             Galunistertib).

          -  Received radiation therapy (or other non-systemic disease therapy) within 2 weeks
             prior to study treatment.

          -  Undergone major surgery within 4 weeks prior to administration of study treatment.

          -  Residual toxicities attributed to prior anti-cancer therapy that are clinically
             significant or unmanaged and >Grade 1 or previous baseline other than neuropathy
             (<=Grade 2), alopecia, and fatigue.

          -  The participant has participated in a clinical trial and has received an
             investigational product within the following time period prior to the first dosing day
             in the current study: 30 days, 5 half-lives or twice the duration of the biological
             effect of the investigational product (whichever is longer).

          -  Exposure to more than 2 investigational anti-cancer medicinal products within 12
             months prior to the first dosing day.

          -  Is known to abuse alcohol or drugs.

          -  Has any psychiatric condition that would prohibit the understanding or rendering of
             informed consent or consistent participation in study procedures.

          -  Has legal incapacity or limited legal capacity.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed overall response rate (ORR) - Investigator assessment
Time Frame:From 6 month after Day 1 of treatment through 3 years maximum
Safety Issue:
Description:The ORR is defined as the percentage of participants with a partial response (PR) or complete response (CR) as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

Secondary Outcome Measures

Measure:Duration of Response (DOR) - Investigator assessment
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:DOR is defined as the time from first documentation of an objective response (CR or PR) according to RECIST v 1.1 assessed by the investigator to the date of first documentation of objective response of disease progression or death due to any cause whichever occurs first.
Measure:Progression-free Survival (PFS) - Investigator assessment
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:PFS according to RECIST v 1.1 assessed by investigator is defined as the time from first administration of study intervention until date of the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurs first.
Measure:Confirmed overall response rate- Independent Review Committee (IRC)
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:ORR is defined as the percentage (%) of participants with a PR or CR as assessed by IRC using RECIST v 1.1.
Measure:Duration of Response - IRC
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:DOR is defined as the time from first documentation of an objective response (CR or PR) according to RECIST v 1.1 assessed by IRC to the date of first documentation of objective response of disease progression or death due to any cause whichever occurs first.
Measure:Progression free survival - IRC
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:PFS according to RECIST v 1.1 assessed by IRC, is defined as the time from first administration of study intervention until date of the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:OS is defined as the time from first administration of study intervention to the date of death due to any cause.
Measure:Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment.
Measure:Number of participants with AEs by their severity
Time Frame:From start of treatment up to 3 years
Safety Issue:
Description:The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v 5.0.
Measure:Concentration observed immediately at the end of infusion (Ceoi) for bintrafusp alfa
Time Frame:Up to 2 years maximum
Safety Issue:
Description:Blood sample will be collected for measurement of serum concentrations of bintrafusp alfa for Ceoi analysis at indicated time points.
Measure:Concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing) (Ctrough) for bintrafusp alfa.
Time Frame:Up to 2 years maximum
Safety Issue:
Description:Blood sample will be collected for measurement of serum concentrations of bintrafusp alfa for Ctrough analysis at indicated time points.
Measure:Number of participants with positive anti-drug antibodies (ADAs) against bintrafusp alfa
Time Frame:Up to 2 years maximum
Safety Issue:
Description:Serum samples will be collected at indicated time points for analysis of ADAs by using tiered testing with validated immunoassay.
Measure:Percentage of participants with positive ADAs against bintrafusp alfa
Time Frame:Up to 2 years maximum
Safety Issue:
Description:Serum samples will be collected at indicated time points for analysis of ADAs.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Bintrafusp Alfa
  • Platinum Agent
  • Response Evaluation Criteria in Solid Tumors
  • Urothelial Cancer
  • M7824

Last Updated

August 11, 2020