Clinical Trials /

A Study to Evaluate Enfortumab Vedotin in Subjects With Previously Treated Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

NCT04225117

Description:

The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR). This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Hypopharyngeal Carcinoma
  • Laryngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Oral Cavity Carcinoma
  • Oropharyngeal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Enfortumab Vedotin in Subjects With Previously Treated Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
  • Official Title: An Open-label, Multicenter, Multicohort, Phase 2 Study to Evaluate Enfortumab Vedotin in Subjects With Previously Treated Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

Clinical Trial IDs

  • ORG STUDY ID: 7465-CL-202
  • NCT ID: NCT04225117

Conditions

  • Locally Advanced or Metastatic Malignant Solid Tumors

Interventions

DrugSynonymsArms
enfortumab vedotinASG-22CECohort 1: HR+/HER2- breast cancer

Purpose

The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR). This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin.

Detailed Description

      This study will consist of 3 periods: screening/baseline, treatment and follow-up.

      Screening/baseline period will take place up to 28 days prior to the first dose of study
      treatment.

      In the treatment period, starting at cycle 1, participants will receive enfortumab vedotin on
      days 1, 8, and 15 every 28-day cycle until one of the treatment discontinuation criteria are
      met. Disease assessment will be performed at screening/baseline and repeated every 8 weeks
      (56 days ± 7 days) from the first dose of study treatment throughout the study until the
      participant has radiologically confirmed disease progression, initiates a new subsequent
      anticancer therapy, dies, withdraws consent, is lost to follow-up or the study closes,
      whichever occurs first.

      Participants who discontinue study treatment for reasons other than radiologically-confirmed
      disease progression by RECIST Version 1.1 will enter into a post treatment follow-up period
      and continue to receive imaging scans every 8 weeks (56 days ± 7 days) until the subject has
      radiologically confirmed disease progression, initiates a new anticancer therapy, dies,
      withdraws consent, is lost to follow-up or the study closes, whichever occurs first.

      After 1 year on study treatment, the frequency of disease assessment will be reduced to every
      12 weeks (84 days ± 7 days).

      After radiologically-confirmed disease progression or initiation of subsequent anticancer
      therapy, whichever occurs first, participants will be contacted every 12 weeks in the
      long-term follow-up period for survival status until death, withdrawal of consent, lost to
      follow-up or study closure, whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: HR+/HER2- breast cancerExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. HR+/HER2- = Hormone receptor-positive/ human epidermal growth factor receptor 2-negative
  • enfortumab vedotin
Cohort 2: Triple negative breast cancer (TNBC)ExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
  • enfortumab vedotin
Cohort 3: Squamous non-small cell lung cancerExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
  • enfortumab vedotin
Cohort 4: Non-squamous non-small cell lung cancerExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
  • enfortumab vedotin
Cohort 5: Head and neck cancerExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
  • enfortumab vedotin
Cohort 6: Gastric; GEJ or esophageal cancerExperimentalParticipants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. GEJ= gastroesophageal junction
  • enfortumab vedotin

Eligibility Criteria

        Inclusion Criteria:

          -  Subject is considered an adult according to local regulation at the time of signing
             the informed consent form (ICF).

          -  Subject has measurable disease by RECIST Version 1.1.

          -  Subject has accessible archival tumor tissue from either the primary tumor or a
             metastatic site, for which source and availability have been confirmed prior to study
             treatment. If no archival tumor tissue is available, the subject will have a biopsy to
             obtain tumor tissue prior to study treatment. If the subject is unable to undergo a
             biopsy due to safety concerns, enrollment into the study must be discussed with the
             medical monitor.

          -  Subject has ECOG performance status of 0 or 1.

          -  Subject has the following baseline laboratory data. If a subject has received a recent
             blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood
             transfusion.

               -  absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L

               -  platelet count ≥ 100 × 10^9/L

               -  hemoglobin ≥ 9 g/dL

               -  serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
                  subjects with Gilbert's disease

               -  creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards
                  or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can
                  also be used instead of CrCl).

               -  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN

          -  Subject agrees not to participate in another interventional study while receiving
             study treatment in the present study.

          -  Additional contraceptive requirements exist for male and female subjects.

        Disease Specific Inclusion Criteria:

          -  Evidence of progression on or after the last regimen received.

          -  Locally advanced or metastatic disease that is not amenable to curative intent
             treatment.

        Cohort 1: HR+/HER2- breast cancer

          -  Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor
             [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast
             cancers and are not considered a candidate for further hormonal therapy. Subject will
             be considered HR+ if biopsies show ≥ 1% expression of ER or PR as per current American
             Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.

          -  Subject has progressed, relapsed, or discontinued for toxicity during or after at
             least 1 prior cytotoxic regimen, either a taxane or anthracycline in the incurable,
             unresectable locally advanced or metastatic setting, and has not received > 2 prior
             lines of cytotoxic therapy in the locally advanced or metastatic setting. No limit
             applies to endocrine therapies.

               -  Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
                  count as a prior cytotoxic regimen if disease recurrence occurred during or
                  within 6 months of completing the regimen.

          -  Subject has progressed, relapsed, or discontinued for toxicity during or after
             receiving endocrine or hormonally directed therapy with cyclin-dependent kinase (CDK)
             inhibitors.

        Cohort 2: triple negative breast cancer (TNBC)

          -  Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal
             TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1%
             expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either
             0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not
             amplified) as per current ASCO/CAP guidelines.

          -  Subject has progressed, relapsed, or discontinued for toxicity during or after at
             least 1 prior cytotoxic regimen, either a taxane or anthracycline in the incurable,
             unresectable locally advanced or metatstatic setting, and has not received > 2 prior
             lines of cytotoxic therapy in the locally advanced or metastatic setting.

               -  Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
                  count as a prior cytotoxic regimen if disease recurrence occurred during or
                  within 6 months of completing the regimen.

          -  Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1)
             or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or
             PD-L1 expression and local treatment guidelines and has progressed or discontinued
             treatment due to toxicity, or therapy is contraindicated for subject.

        Cohort 3: squamous non-small cell lung cancer (NSCLC)

          -  Subject has histologically or cytologically-confirmed squamous NSCLC.

               -  Subjects with mixed histology NSCLC are eligible provided there is not any
                  component of neuroendocrine histology.

               -  Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma
                  kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations
                  are eligible if treated with mutation targeted therapy and have progressed,
                  relapsed, or discontinued treatment due to toxicity.

          -  Subject has either:

               -  progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum
                  based therapy for locally advanced or metastatic disease, and has not received >
                  2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting.
                  (a.) Maintenance therapy does not constitute a new chemotherapy regimen provided
                  there was no progression after the initial platinum-based regimen.(b.) Changing
                  chemotherapy agents during platinum-based treatment for the management of
                  toxicities does not constitute a new chemotherapy regimen provided no progression
                  had occurred while on the initial therapy, or

               -  progressed or relapsed within 6 months of last dose of platinum-based adjuvant,
                  neoadjuvant, or concomitant chemoradiation regimen for early stage or locally
                  advanced stage disease.

          -  Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1)
             or anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or PD-L1
             expression and local treatment guidelines and has progressed, relapsed, or
             discontinued treatment due to toxicity, or therapy is contraindicated for subject.

        Cohort 4: non-squamous non-small cell lung cancer

          -  Subject has histologically- or cytologically-confirmed non-squamous NSCLC.

               -  Subjects with mixed histology NSCLC are eligible provided there is not any
                  component of neuroendocrine histology.

               -  Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are
                  eligible if treated with mutation targeted therapy and have progressed, relapsed,
                  or discontinued treatment due to toxicity.

          -  Subject has either:

               -  progressed, relapsed, or discontinued treatment due to toxicity after 1
                  platinumbased therapy for locally advanced or metastatic disease, and has not
                  received > 2 prior lines of cytotoxic therapy in the locally advanced or
                  metastatic setting.(a.) Maintenance therapy does not constitute a new
                  chemotherapy regimen provided there was no progression after the initial
                  platinum-based regimen. (b.) Changing chemotherapy agents during platinum-based
                  treatment for the management of toxicities does not constitute a new chemotherapy
                  regimen provided no progression has occurred while on the initial therapy, or

               -  progressed or relapsed within 6 months of last dose of platinum-based adjuvant,
                  neoadjuvant, or concomitant chemoradiation regimen for early stage or locally
                  advanced stage disease.

          -  Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
             tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
             relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
             subject.

        Cohort 5: head and neck cancer

          -  Subject has histologically- or cytologically-confirmed head and neck cancer.

               -  Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
                  larynx; tumors arising from the nasopharynx are excluded.

          -  Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
             platinum-based therapy for locally advanced or metastatic disease, and has not
             received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic
             setting.

               -  Platinum regimens administered as part of multimodal therapy in the curative
                  setting will count as a regimen if relapse occurred ≤ 6 months after completion.

          -  Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
             tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
             relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
             subject.

        Cohort 6: gastric or gastroesophageal junction (GEJ) or esophageal cancer

          -  Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal
             cancer.

          -  Subject has progressed, relapsed, or discontinued due to toxicity after 1
             platinum-based therapy for locally advanced or metastatic disease, and has not
             received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic
             setting.

               -  Neoadjuvant or adjuvant regimens will count as a prior regimen if relapsed or
                  progressed ≤ 6 months after completion.

          -  Subject must have received a HER2 directed therapy if known to have HER2 positive
             cancer.

        Exclusion Criteria:

          -  Subject has preexisting sensory or motor neuropathy Grade ≥ 2.

          -  Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
             metastases are permitted on study if all the following are true:

               -  CNS metastases have been clinically stable for ≥ 6 weeks prior to screening

               -  If requiring steroid treatment for CNS metastases, the subject is on a stable
                  dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks

               -  Baseline imaging scans show no evidence of new or enlarged brain metastasis

               -  Subject does not have leptomeningeal disease

          -  Subject has ongoing clinically significant toxicity (Grade 2 or higher with the
             exception of alopecia) associated with prior treatment (including systemic therapy,
             radiotherapy or surgery).

          -  Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or
             panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis,
             uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs
             requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), are
             excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or
             panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of
             hormone replacement therapy (if indicated).

          -  Subject has a history of uncontrolled diabetes mellitus within 3 months before the
             first dose of study treatment. Uncontrolled diabetes is defined as hemoglobin A1c
             (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria
             or polydipsia) that are not otherwise explained.

          -  Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E
             (MMAE) based antibody-drug conjugates (ADCs).

          -  Subject has a second malignancy diagnosed within 3 years before first dose of study
             drug, or any evidence of residual disease from a previously diagnosed malignancy.
             Subjects with non-melanoma skin cancer, localized prostate cancer treated with
             curative intent with no evidence of progression, low-risk or very low-risk (per
             standard guidelines) localized prostate cancer under active surveillance/watchful
             waiting without intent to treat, or carcinoma in situ of any type (if complete
             resection was performed) are allowed.

          -  Subject is currently receiving systemic antimicrobial treatment for viral, bacterial,
             or fungal infection at the time of first dose of study treatment. Routine
             antimicrobial prophylaxis is permitted.

          -  Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg]
             reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is
             detected).

          -  Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or
             2).

          -  Subject has documented history of a cerebral vascular event (stroke or transient
             ischemic attack), unstable angina, myocardial infarction or cardiac symptoms
             (including congestive heart failure) consistent with New York Heart Association Class
             III-IV within 6 months prior to the first dose of study drug.

          -  Subject has major surgery within 4 weeks prior to first dose of study drug.

          -  Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or
             antitumor treatment with immunotherapy that is not completed 2 weeks prior to first
             dose of study drug.

          -  Subject has known hypersensitivity to enfortumab vedotin or to any excipient contained
             in the drug formulation of enfortumab vedotin (including histidine, trehalose
             dihydrate and polysorbate 20) OR subject has known hypersensitivity to
             biopharmaceutical produced in Chinese hamster ovary cells.

          -  Subject has known active keratitis or corneal ulcerations. Subject with superficial
             punctate keratitis is allowed if the disorder is being adequately treated.

          -  Subject has any condition which makes the subject unsuitable for study participation.
      
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) (Complete Response (CR) and Partial Response(PR)) per RECIST V1.1 per investigator assessment
Time Frame:Up to 3 years
Safety Issue:
Description:Confirmed ORR is defined as the proportion of participants whose objective response is a confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 per investigator assessment.

Secondary Outcome Measures

Measure:Duration of Response (DOR) per RECIST V1.1 as per investigator assessment
Time Frame:Up to 3 years
Safety Issue:
Description:DOR is defined as the time from the date of first documented response (CR or PR that is subsequently confirmed) to the date of first documented progressive disease (PD) per RECIST version 1.1 or death due to any cause, whichever occurs first. DOR will only be calculated for participants achieving a confirmed CR or PR.
Measure:Disease Control Rate (DCR) per RECIST V1.1 as per investigator assessment
Time Frame:Up to 3 years
Safety Issue:
Description:DCR is defined as the proportion of participants whose Best Overall Response (BOR) is confirmed CR or PR or stable disease (SD).
Measure:Duration of Progression Free Survival (PFS) per RECIST V1.1 as per investigator assessment
Time Frame:Up to 3 years
Safety Issue:
Description:PFS is defined as the time from start of study treatment to first documentation of PD per RECIST version 1.1 or death due to any cause, whichever comes first.
Measure:Duration of Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:OS is defined as the time from start of study treatment to date of death due to any cause.
Measure:Number of participants with Adverse Events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description:AEs will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered enfortumab vedotin, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of enfortumab vedotin whether or not considered related to the enfortumab vedotin. An AE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events.
Measure:Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with potentially clinically significant laboratory values.
Measure:Number of participants with vital sign abnormalities and /or adverse events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with potentially clinically significant vital sign values.
Measure:Number of participants with routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with potentially clinically significant ECG values.
Measure:Number of participants at each grade of the Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time Frame:Up to 2 years
Safety Issue:
Description:The ECOG scale will be used to assess performance status. Grades range from 0 (equals fully active, able to carry on all pre-disease performance without restriction), and 5 (equals dead).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • Squamous NSCLC
  • Triple negative breast cancer (TNBC)
  • ASG-22CE
  • non-small cell lung cancer (NSCLC)
  • Hormone receptor-positive/ human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer
  • non-squamous NSCLC
  • locally advanced or metastatic malignant solid tumors
  • Head and neck cancer
  • EV-202
  • Gastric or gastroesophageal junction (GEJ) or esophageal cancer

Last Updated

January 9, 2020