EV 301
What is the study design of EV 301?
EV vs chemotherapy after prior platinum-based chemotherapy and PD-(L)1 inhibitor in la/mUC
Randomized 1:1 to EV 1.25mg/kg IV vs chemo
Describe EV 103 Cohort A
1L Cis-ineligible la/mUC
Pembro D1 + EV D1 and D8
Describe EV 103 Cohort K
Randomized cohort of EV or EV+pembro in la/mUC 1L cis-ineligible
When does onset of skin reactions usually occur with EV?
Typically within the first cycle
What are the preselected therapies in the chemo arm of EV 301?
Docetaxel 75mg/m2
Paclitaxel 175mg/m2
Vinflunine 320mg/m2
What were the original response rates in EV 103 Cohort A?
ORR 73%; CR 15.6%
DOR not reached at 10mo
mPFS 12.3mo
mOS not reached
What is the dosing schedule in EV 103 Cohort K and why?
EV D1 and D8 Q3W
This is comparable to EV monotherapy on a 4 week schedule (D1, D8, D15 Q28 days)
Aligns with pembro dosing
When does onset of hyperglycemia usually occur with EV?
Typically within the first cycle
What were the results of EV vs chemo in EV 301 ?
ORR 40.6% vs 17.9%
CR 4.9% vs 2.7%
PR 35.8% vs 15.2%
DCR 17.9% vs 53.4%
PFS 5.55mo vs 3.71mo
OS 12.88mo vs 8.97mo
DOR 7.39mo vs 8.11mo
What were the median number of cycles in EV 103 Cohort A?
9 cycles
What is the rationale for combining EV with a CPI?
ADCs linked to MMAE induce ICD in preclinical & in vitro data, ICD releases innate immune-activating molecules resulting in APC activation and presentation of tumor antigens to T cells
T cells mount antigen-specific response augmented by PD-1/L1 inhibitors which may enhance anti-tumor activity
When does onset of PN usually occur with EV?
Usually around cycle 5 (~4.6mo)
What were the most common grade 3 or higher TRAEs in EV 301?
maculopapular rash, decreased neutrophil count, fatigue
What are the updated response rates in EV 103 Cohort A?
mDOR 25.6mo (53% of responders had DOR at 24mo)
DCR 93.3%
mPFS 12.3mo
mOS not reached
OS at 24mo is 56.3%
Is EV 103 Cohort K enrolling?
No, it is fully enrolled and we are awaiting data readout
What are the parameters around blood glucose levels and dosing EV?
Blood glucose greater than 250, withhold until lower than 250 then resume EV at the same dose level
What was the median treatment exposure in EV 301?
5mo vs 3.5 mo
What were the rates of PN, Rash, and Hyperglycemia in EV 103 Cohort A?
PN 56% (all grade); 4% >/= grade 3
Rash 62% (all grade); 13% >/= grade 3
Hyperglycemia 11% (all grade); 7% >/= grade 3
Why is there an EV monotherapy cohort in EV 103 Cohort K and not a CPI alone cohort?
Done to better understand contribution of components
Never meant to be a comparative study design vs CPI alone
What is the recommended Dose Reduction Schedule for EV?
Starting dose: 1.25mg/kg up to 125mg
1st reduction: 1.0mg/kg up to 100mg
2nd reduction: 0.75mg/kg up to 75mg
3rd reduction: 0.5mg/kg up to 50mg