An open-label, randomized, controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab, versus chemotherapy alone in previously untreated locally advanced or metastatic urothelial cancer
- Conditions
- Urothelial cancer / Bladder cancer10038364
- Registration Number
- NL-OMON55964
- Lead Sponsor
- Seagen, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 36
1. Subjects must have histologically documented, unresectable locally advanced
or metastatic urothelial carcinoma (i.e., cancer of the bladder, renal pelvis,
ureter, or urethra). Subjects with squamous or sarcomatoid differentiation or
mixed cell types are eligible.
2. Subjects must have measurable disease by investigator assessment according
to RECIST v1.1.
a. Subjects with prior definitive radiation therapy must have measurable
disease per RECIST v1.1 that is outside the radiation field or has demonstrated
unequivocal progression since completion of radiation therapy
3. Subjects must not have received prior systemic therapy for locally advanced
or metastatic urothelial carcinoma with the following exceptions:
a. Subjects that received neoadjuvant chemotherapy with recurrence >12
months from completion of therapy are permitted
b. Subjects that received adjuvant chemotherapy following cystectomy with
recurrence >12 months from completion of therapy are permitted
4. Subjects must be considered eligible to receive cisplatin- or
carboplatin-containing chemotherapy, in the investigator*s judgement.
a. Subjects will be considered cisplatin-ineligible, and will receive
carboplatin, if they meet at least one of the following criteria:
i. GFR <60 mL/min but >=30 mL/min (measured by the Cockcroft-Gault
formula, Modification of Diet in Renal Disease [MDRD] or 24-hour urine)
· Subjects with a GFR >=50 mL/min and no other cisplatin ineligibility
criteria may be considered cisplatin-eligible based on the investigator*s
clinical judgement
ii. ECOG or WHO performance status of 2 (refer to Inclusion 7 for
additional criteria for ECOG 2 subjects)
iii. NCI CTCAE Grade >=2 audiometric hearing loss
iv. NYHA Class III heart failure
5. Subjects must be age 18 years or older or considered an adult by local
regulations.
6. Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a
biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing
prior to randomization. If adequate archival tumor sample is not available, or
evaluable, a new biopsy sample may be performed.
7. Subjects must have an ECOG Performance Status score of 0, 1, or 2.
a. Subjects with ECOG performance status of 2 must additionally meet the
following criteria:
i. Hemoglobin >=10 g/dL
ii. GFR >=50 mL/min
iii. May not have NYHA Class III heart failure
8. Subjects must have adequate hematologic and organ function as defined by the
baseline laboratory values in Table 5 (see protocol)
9. Female subjects of childbearing potential must meet the following conditions:
· Agree not to try to become pregnant during the study and for at least 6
months after the final dose of study drug.
· Must have a negative urine or serum pregnancy test (minimum sensitivity of 25
mIU/mL or equivalent units of beta human chorionic gonadotropin [β-hCG]) within
1 day prior to administration of the drug. Female subjects with false positive
results and documented verification of negative pregnancy status are eligible
for participation.
· If heterosexually active, agree to abstinence (if in line with the usual
preferred lifestyle of the subject) or consistently use a condom plus 1 form of
highly effective birth control per locally accepted standards starting a
1. Subjects who have previously received enfortumab vedotin or other MMAE-based
ADCs.
2. Subjects who have received prior treatment with a PD-(L)-1 inhibitor for any
malignancy, including earlier stage UC, defined as a PD-1 inhibitor or PD-L1
inhibitor.
3. Subjects who have previously received any prior treatment with an agent
directed to another stimulatory or co inhibitory T-cell receptor.
4. Subjects who have received anti-cancer treatment with chemotherapy,
biologics, or investigational agents not otherwise prohibited by exclusion
criterion 1-3 that is not completed 4 weeks prior to first dose of study
treatment.
5. Subjects with uncontrolled diabetes.
6. Subjects with an estimated life expectancy <12 weeks
7. Subjects with ongoing sensory or motor neuropathy Grade 2 or higher.
8. Subjects with active CNS metastases. Subjects with treated CNS metastases
are permitted on study if all of the following are true: a) CNS metastases have
been clinically stable for at least 4 weeks prior to screening and baseline
scans show no evidence of new or enlarged metastasis; b) the subject is on a
stable dose of <=10 mg/day of prednisone or equivalent for at least 2 weeks (if
requiring steroid treatment); c) subject does not have leptomeningeal disease.
9. Subjects with ongoing clinically significant toxicity associated with prior
treatment (including radiotherapy or surgery) that has not resolved to <= Grade
1 or returned to baseline.
10. Currently receiving systemic antimicrobial treatment for active infection
(viral, bacterial, or fungal) at the time of randomization. Routine
antimicrobial prophylaxis is permitted.
11. Subjects who have a known history of hepatitis B (defined as HBsAg
reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative]
is detected) infection. No testing for hepatitis B and hepatitis C is required
unless mandated by local health authority. Subjects who have been curatively
treated for hepatitis C infection are permitted if they have documented
sustained virologic response of 12 weeks.
12. Has a known history of human immunodeficiency virus (HIV) infection.
Testing is not required unless mandated by the local health authority.
13. Subjects with conditions requiring high doses of steroids (>10 mg/day of
prednisone or equivalent) or other immunosuppressive medications are excluded.
Inhaled or topical steroids are permitted in the absence of active autoimmune
disease. Physiologic replacement doses of corticosteroids are permitted for
subjects with adrenal insufficiency.
14. Subjects with a history of another invasive malignancy within 3 years
before the first dose of study drug, or any evidence of residual disease from a
previously diagnosed malignancy (eligible exceptions see protocol).
15. Subjects with a documented history of a cerebral vascular event (stroke or
transient ischemic attack), unstable angina, myocardial infarction, or cardiac
symptoms consistent with NYHA Class IV within 6 months prior to randomization.
16. Subjects who have received radiotherapy within 2 weeks prior to
randomization.
17. Subjects who have received major surgery (defined as requiring general
anesthesia and >24-hour inpatient hospitalization) within 3 weeks prior to
randomization.
18. Subjects with known severe (>= Grade 3) hypersen
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Dual Primary Endpoints<br /><br>* PFS per RECIST v1.1 by BICR<br /><br>* OS</p><br>
- Secondary Outcome Measures
Name Time Method