A Pilot Trial of Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma
A Pilot Trial of Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma
This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab.
This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab. Approximately 50 patients will be enrolled to the main EV monotherapy cohort who are scheduled to receive EV as standard of care. Additionally, an exploratory arm will enroll 20 patients with metastatic urothelial cancer who are scheduled to receive EV in combination with pembrolizumab as standard of care. All subjects will have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and meet baseline laboratory data as outlined in the section 4.1.
Inclusion Criteria:
EV monotherapy main cohort:
Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
Planned to receive EV as standard treatment for advanced urothelial cancer
ECOG performance status 0-2
Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
Age > 18 years.
Ability to understand and willingness to sign a written informed consent and HIPAA consent document
Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded [FFPE] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
Normal organ and marrow function as defined below.
EV/pembrolizumab arm:
Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
Planned to receive EV/pembrolizumab as standard treatment for advanced urothelial cancer
ECOG performance status 0-2
Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
Age > 18 years.
Ability to understand and willingness to sign a written informed consent and HIPAA consent document
Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed, paraffin embedded [FFPE] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
Normal organ and marrow function as defined below.
Exclusion Criteria:
Both EV monotherapy and EV/pembrolizumab arms:
Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.
Grade 2 or higher baseline sensory or motor neuropathy.
Uncontrolled diabetes (HbA1c >8%)
Patients with uncontrolled and untreated central nervous system (CNS) metastases.
Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed.
Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin.
History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
Prior allogeneic stem cell or solid organ transplant.
Other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
Patients with active tuberculosis.
Pregnant or breast feeding
EV/Pembrolizumab exploratory arm only:
Patients who received prior immunotherapy for metastatic urothelial carcinoma (mUC) or for an alternative malignancy are eligible unless they developed an immune related adverse event while on therapy requiring cessation of therapy or use of disease modifying agents, corticosteroids, or immunosuppressive drugs.
History of autoimmune diseases. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
On high dose steroids at the time of study enrollment, defined as >20mg prednisone (or bioequivalent), including steroids used for management of intracranial lesions. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.