Clinical Trials /

Sacituzumab Govitecan Plus EV in Metastatic UC

NCT04724018

Description:

This research study will assess what doses of Sacituzumab Govitecan and Enfortumab Vedotin can be safely combined in the treatment of metastatic urothelial carcinoma (mUC). The names of the study drugs in this investigational combination are: - Enfortumab Vedotin - Sacituzumab Govitecan

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sacituzumab Govitecan Plus EV in Metastatic UC
  • Official Title: Sacituzumab Govitecan Plus Enfortumab Vedotin for Metastatic Urothelial Carcinoma Progressing on Platinum-based Chemotherapy and PD1/L1 Inhibitors: the Double Antibody Drug Conjugate (DAD) Phase I Trial

Clinical Trial IDs

  • ORG STUDY ID: 20-614
  • NCT ID: NCT04724018

Conditions

  • Urothelial Cancer
  • Metastatic Urothelial Carcinoma
  • Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Bladder Cancer

Interventions

DrugSynonymsArms
Sacituzumab Govitecan (SG)TrodelvyDose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV),
Enfortumab vedotin-ejfv (EV)PadcevDose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV),

Purpose

This research study will assess what doses of Sacituzumab Govitecan and Enfortumab Vedotin can be safely combined in the treatment of metastatic urothelial carcinoma (mUC). The names of the study drugs in this investigational combination are: - Enfortumab Vedotin - Sacituzumab Govitecan

Detailed Description

      This study is a single-center, open-label, nonrandomized phase I trial testing the safety and
      efficacy as well as defining the appropriate dose for future studies of Sacituzumab Govitecan
      and Enfortumab for people with metastatic urothelial carcinoma (mUC) progressing on
      platinum-based chemotherapy and PD1/L1 inhibitors

      The U.S. Food and Drug Administration (FDA) has approved Enfortumab Vedotin for the treatment
      of metastatic urothelial carcinoma (mUC) (bladder cancer). The FDA has not approved
      Sacituzumab Govitecan for metastatic urothelial carcinoma (mUC) (bladder cancer) but it has
      been approved for other uses. The FDA has approved Sacituzumab Govitecan to treat a type of
      breast cancer at this time. Sacituzumab Govitecan has appeared promising in patients with
      bladder cancer that has spread and works by a different mechanism than Enfortumab Vedotin.
      Therefore, the researchers believe that combining these 2 drugs may control the cancer better
      than each drug does on its own.

      This will be done through testing different combinations and checking for serious side
      effects; if there are no serious side effects a different dose combination will be explored.
      Once the best combination has been determined, the study will look to see how effective (how
      well the drug works) it is in slowing down the growth of metastatic urothelial carcinoma
      (mUC) progressing on platinum-based chemotherapy and PD1/L1 inhibitors and define the most
      appropriate level of the drugs to use for further studies.

      The research study procedures include screening for eligibility, study treatment, and safety
      follow-up visits, in addition to general health status follow-up after study treatment.

      Participants will receive study treatment for as long as they do not have serious side
      effects and their disease does not get worse. However, the duration may vary depending on how
      long the treatment works to control the cancer and how someone's body tolerates the side
      effects.

      Immunomedics, a pharmaceutical company, is supporting this research study by providing
      funding for the research study, tests required for research purposes only, and the study drug
      Sacituzumab Govitecan.

      It is expected that up to 24 people will take part in this research study.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV),ExperimentalParticipants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of a 21-day study cycle. Dose escalation and de-escalation for the Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination will be guided using the Bayesian optimal interval (BOIN) design with up to 4 dose level escalations.
  • Sacituzumab Govitecan (SG)
  • Enfortumab vedotin-ejfv (EV)

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically documented confirmed predominant urothelial
             carcinoma (i.e. of the bladder, renal pelvis, ureter or urethra). Patients with
             squamous differentiation or mixed cell types are eligible; small-cell carcinoma is not
             allowed.

        Patients with locally advanced unresectable disease are eligible.

          -  Patient must have received prior treatment with a checkpoint inhibitor (CPI) in
             locally advanced or metastatic urothelial cancer setting. Patients who received CPI
             therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease
             either during or within 3 months of therapy completion are eligible. A CPI is defined
             as a PD-1 or PD-L1 inhibitor.

          -  Patients must have received prior treatment with platinum containing therapy defined
             as within the adjuvant/neoadjuvant setting with recurrent or progressive disease
             within 12 months or receiving treatment with platinum in locally advanced or
             metastatic setting.

          -  Age ≥18 years. Because no dosing or adverse event data are currently available on the
             use of EV in combination with SG in participants <18 years of age, children are
             excluded from this study, but will be eligible for future pediatric trials.

          -  ECOG performance status 0-1.

          -  Participants must have adequate organ and marrow function as defined below:

               -  Leukocytes ≥3,000/mcL

               -  Absolute neutrophil count ≥1,500/mcL

               -  Platelets ≥100,000/mcL

               -  Total bilirubin ≤ institutional upper limit of normal (ULN)

               -  AST(SGOT)/ALT(SGPT) ≤2.5x institutional ULN OR

                  ≤5x ULN with liver metastases and serum albumin > 3 g/dL

               -  Glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (by Cockcroft Gault formula)

          -  Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial.

          -  For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
             viral load must be undetectable on suppressive therapy, if indicated.

          -  Participants with a history of hepatitis C virus (HCV) infection must have been
             treated and cured. For participants with HCV infection who are currently on treatment,
             they are eligible if they have an undetectable HCV viral load.

          -  Participants with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
             function using the New York Heart Association Functional Classification. To be
             eligible for this trial, participants should be class 2B or better.

          -  Have measurable disease by computed tomography (CT) or magnetic resonance imaging
             (MRI) as per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1
             criteria). Tumor lesions situated in a previously irradiated area are considered
             measurable if progression has been demonstrated in such lesions

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication.
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required

          -  Female subjects of childbearing potential must be willing to use 2 methods of birth
             control or be surgically sterile or abstain from heterosexual activity for the course
             of the study through 6 months after the last dose of study medication. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for >2 years

          -  The effects of SG and EV on the developing human fetus are unknown. Women of
             child-bearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation. Should a woman become pregnant or suspect she is pregnant
             while she or her partner is participating in this study, she should inform her
             treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of SG administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

        Subjects meeting any of the following exclusion criteria at Screening/Day 1 of treatment
        will not be enrolled in the study.

          -  Women who are pregnant or lactating. Pregnant women are excluded from this study
             because SG and EV have potential for teratogenic or abortifacient effects. Because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with EV or SG, breastfeeding should be discontinued if the
             mother is treated on protocol.

          -  Have had a prior anti-cancer biologic agent within 4 weeks prior to Cycle 1 Day 1
             (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation
             therapy within 2 weeks prior to C1D1. Subjects participating in observational studies
             are eligible.

          -  Presence of any toxicities attributed to prior anti-cancer therapy that are not
             resolved to Grade 1 or baseline that could impose serious risk for complications
             before administration of study drug agent

               -  Note: If subjects received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy.

          -  Have previously received topoisomerase 1 inhibitors, SG or EV

          -  Have an active second malignancy. Subjects with a history of malignancy that have been
             completely treated, with no evidence of active cancer for 3 years prior to start of
             therapy on trial (Cycle 1 Day 1 [C1D1]), or subjects with surgically-cured tumors with
             low risk of recurrence are allowed to enroll.

          -  Have known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they have stable CNS disease for at least 4 weeks prior to the first dose of study
             drug and all neurologic symptoms have returned to baseline, have no evidence of new or
             enlarging brain metastases, and are taking ≤20 mg/day of prednisone or its equivalent.

        All subjects with carcinomatous meningitis are excluded regardless of clinical stability.

          -  Have active cardiac disease, defined as:

               -  Myocardial infarction or unstable angina pectoris within 6 months prior to C1D1

               -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
                  ventricular fibrillation), high-grade atrioventricular block, or other cardiac
                  arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation
                  that is well controlled with antiarrhythmic medication); history of QT interval
                  prolongation

               -  New York Heart Association (NYHA) Class III or greater congestive heart failure
                  or left ventricular ejection fraction of < 40%

          -  Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
             or gastrointestinal (GI) perforation within 6 months of C1D1

          -  Have active serious infection requiring antibiotics (Contact medical monitor for
             clarification)

          -  Have other concurrent medical or psychiatric conditions that, in the Investigator's
             opinion, may be likely to confound study interpretation or prevent completion of study
             procedures and follow-up examinations.

          -  High dose systemic corticosteroids (≥20 mg of prednisone or its equivalent) are not
             allowed within 2 weeks prior to C1D1.

          -  Participants who are receiving any other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to EV or SG or any excipient contained in the drug formulations (including
             2-(N-morpholino) ethane sulfonic acid (MES), histidine, treahalose dihydrate
             polysorbate 80 and polysorbate 20).

          -  Participants with uncontrolled intercurrent illness.

          -  Participants with psychiatric illness/social situations that would limit compliance
             with study requirements.

          -  Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin
             A1C >8% or 7-8% with associated diabetes symptoms that are otherwise not explained

          -  Uncontrolled tumor related bone pain or impending spinal cord compression.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination
Time Frame:21 days
Safety Issue:
Description:The Maximum Tolerated Dose (MTD) in mg of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination is assessed.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:21 days
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Measure:Rate of Complete Responses (CR)
Time Frame:21 days
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Measure:Rate of Partial responses (PR)
Time Frame:21 days
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Measure:Rate of participants with progressive disease
Time Frame:21 days
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Measure:Overall survival (OS) Rate
Time Frame:21 days
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Urothelial cancer
  • Metastatic Urothelial Carcinoma
  • Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Bladder Cancer

Last Updated

January 26, 2021