Enfortumab vedotin-ejfv (Padcev™) is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated for the treatment for adult individuals with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. This indication was approved under accelerated approval based on tumor response rate.
EV-201 was a single-arm, multi-center phase II trial which enrolled 125 participants with la/mUC into 2-cohort study, for individuals who were treated with prior platinum-containing chemotherapy and anti-PD-1/L1 therapy (Cohort 1), or anti-PD-1/L1 therapy and no prior chemotherapy and were cisplatin-ineligible (Cohort 2). The median age was 69 years (range: 40 to 84 years), 70% were male, and 85% were Caucasian. All participants had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (32%) or 1 (68%). Ninety percent had visceral metastases including 40% of the participants presenting with liver metastases. Nectin-4 expression was present in all who were tested (n=120). The median number of prior systemic therapies was 3 (range: 1 to 6). 46% of participants received prior PD-1 inhibitor, 42% received prior PD-L1 inhibitor, and an additional 13% received both PD-1 and PD-L1 inhibitors. 66% of participants received prior cisplatin based regimens, 26% received prior carboplatin-based regimens, and an additional 8% received both cisplatin and carboplatin-based regimens.
The primary efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR) assessed by a blinded independent central review (BICR). The researchers report results of 44% ORR (N=125; 95 % CI:35.1%,53.2%), with a median duration of response of 7.6 months, and a maximum duration of 15.6 months. The ORR consisted of confirmed complete response ([CR], 12%) and partial response ([PR], 32%), respectively. CR was defined as the disappearance of all target lesions. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, utilizing the baseline sum diameters as a reference. Treatment continued until disease progression or unacceptable toxicity. The median duration of follow-up was 10.2 months (range, 0.5 to 16.5 months). The study included secondary endpoints: progression-free survival, and overall survival.
Additional studies are warranted to evaluate if the specific etiology of carcinoma characteristics (epithelial, squamous differentiation, or other histological variants) within this extremely comprised population influences objective outcomes (e.g., overall survival, progression-free survival).
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
C65.1 Malignant neoplasm of right renal pelvis
C65.2 Malignant neoplasm of left renal pelvis
C65.9 Malignant neoplasm of unspecified renal pelvis
C66.1 Malignant neoplasm of right ureter
C66.2 Malignant neoplasm of left ureter
C66.9 Malignant neoplasm of unspecified ureter
C67.0 Malignant neoplasm of trigone of bladder
C67.1 Malignant neoplasm of dome of bladder
C67.2 Malignant neoplasm of lateral wall of bladder
C67.3 Malignant neoplasm of anterior wall of bladder
C67.4 Malignant neoplasm of posterior wall of bladder
C67.5 Malignant neoplasm of bladder neck
C67.6 Malignant neoplasm of ureteric orifice
C67.8 Malignant neoplasm of overlapping sites of bladder
C67.9 Malignant neoplasm of bladder, unspecified
C68.0 Malignant neoplasm of urethra
C68.8 Malignant neoplasm of overlapping sites of urinary organs
C68.9 Malignant neoplasm of urinary organ, unspecified
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics