A Study to Evaluate Enfortumab Vedotin in Subjects with Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
- Conditions
- ocally advanced or metastatic malignant solid tumors
- Registration Number
- JPRN-jRCT2080225095
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- recruiting
- Sex
- All
- Target Recruitment
- 320
1. Subject is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
2. Subject has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
3. 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.
For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for programmed cell death-ligand 1 (PD-L1) central testing during screening if no local PD-L1 test result is available. Central test result for PD-L1 will be required prior to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming CPS >=1, archival or fresh tissue sample for exploratory analysis should be submitted within 5 days of enrollment.
4. Subject has eastern cooperative oncology group (ECOG) performance status of 0 or 1.
5. 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.
Disease Specific Inclusion Criteria:
A line of therapy is defined as a course of treatment at the end of which there was disease progression, toxicity, or in the investigator's opinion, maximum benefit has been achieved. If the subject discontinued therapy due to any other reason but progressed without receiving other treatment, this would be considered a line of therapy.
Cohort 1: HR+/HER2- breast cancer
6. Subject has evidence of radiographic progression on or after the last regimen received.
7. 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.
8. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
9. Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or incurable, locally advanced or metastatic setting.
a. 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.
10. Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen 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. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
11. Subject has progressed, relapsed, or discontinued for toxicity during or after receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required.
Cohort 2: triple negative breast cancer (T
For all cohorts:
1. Subject has preexisting sensory or motor neuropathy Grade >= 2.
2. Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
a. CNS metastases have been clinically stable for >= 6 weeks prior to screening
b. If requiring steroid treatment for CNS metastases, the subject is on a stable dose =< 20 mg/day of prednisone or equivalent for >= 2 weeks
c. Baseline imaging scans show no evidence of new or enlarged brain metastasis
d. Subject does not have leptomeningeal disease
3. 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).
4. 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).
5. Subject has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes (within 3 months before first dose) 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. The lowest HbA1c during the screening period will be used to determine eligibility.
6. Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE) based antibody-drug conjugates (ADCs).
7. 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.
8. 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.
9. 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).
10. Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
11. 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.
12. Subject has major surgery within 4 weeks prior to first dose of study drug.
13. 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.
14. Subject has known hypersensiti
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method