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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04225117
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : November 20, 2020
Sponsor:
Collaborator:
Seagen Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Malignant Solid Tumors Drug: enfortumab vedotin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 9, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: HR+/HER2- breast cancer

Participants 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

Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE

Experimental: Cohort 2: Triple negative breast cancer (TNBC)
Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE

Experimental: Cohort 3: Squamous non-small cell lung cancer
Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE

Experimental: Cohort 4: Non-squamous non-small cell lung cancer
Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE

Experimental: Cohort 5: Head and neck cancer
Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.
Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE

Experimental: Cohort 6: Gastric; GEJ or esophageal cancer

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

GEJ= gastroesophageal junction

Drug: enfortumab vedotin
intravenous (IV) infusion
Other Name: ASG-22CE




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Duration of Response (DOR) per RECIST V1.1 as per investigator assessment [ Time Frame: Up to 3 years ]
    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.

  2. Disease Control Rate (DCR) per RECIST V1.1 as per investigator assessment [ Time Frame: Up to 3 years ]
    DCR is defined as the proportion of participants whose Best Overall Response (BOR) is confirmed CR or PR or stable disease (SD).

  3. Duration of Progression Free Survival (PFS) per RECIST V1.1 as per investigator assessment [ Time Frame: Up to 3 years ]
    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.

  4. Duration of Overall Survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time from start of study treatment to date of death due to any cause.

  5. Number of participants with Adverse Events (AEs) [ Time Frame: Up to 2 years ]
    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.

  6. Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 2 years ]
    Number of participants with potentially clinically significant laboratory values.

  7. Number of participants with vital sign abnormalities and /or adverse events (AEs) [ Time Frame: Up to 2 years ]
    Number of participants with potentially clinically significant vital sign values.

  8. Number of participants with routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) [ Time Frame: Up to 2 years ]
    Number of participants with potentially clinically significant ECG values.

  9. Number of participants at each grade of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Up to 2 years ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04225117


Contacts
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Contact: Astellas Pharma Global Development, Inc. 800-888-7704 astellas.registration@astellas.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Seagen Inc.
Investigators
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Study Director: Medical Director Astellas Pharma Global Development, Inc.
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT04225117    
Other Study ID Numbers: 7465-CL-202
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: November 20, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
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
Additional relevant MeSH terms:
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Neoplasms