Tecentriq’s potential in first-line bladder cancer remains something of an unknown quantity, notwithstanding this morning’s toplining of the Imvigor-130 study by Roche. The company said this phase III trial had read out positively for progression-free survival, a co-primary endpoint, with an “encouraging” though still immature overall survival result. The complete numbers, including a split by subjects’ PD-L1 status, will be crucial to determining the true relevance of this trial, which was last year responsible for Tecentriq’s first-line bladder cancer use in cisplatin-ineligible patients being limited to those expressing PD-L1 at ≥5%. That was spurred by a US FDA safety alert contending that an earlier interim analysis of Imvigor-130 had shown low PD-L1 expressers doing worse on Tecentriq than on chemo. The drug can still be used first line irrespective of PD-L1 status in patients ineligible for any platinum-containing chemo, and depending on which subgroups are driving the overall result the full Imvigor-130 data could make the regulator decide to strengthen or relax the current label. Given that second-line accelerated approval was separately thrown into doubt by the failure of the Imvigor-211 trial anything is still possible.
|Tecentriq's mixed fortunes in urothelial bladder cancer|
|Imvigor-210 cohort 2||ORR 14.8%; ORR 26.0% in PD-L1 ≥5%, 9.5% in PD-L1 <5%||Basis of US accelerated approval in 2nd-line all-comers (May 2016)|
|Imvigor-210 cohort 1||ORR 23.5%; ORR 28.1% in PD-L1 ≥5%, 21.8% in PD-L1 <5%||Basis of US accelerated approval in 1st-line cisplatin-ineligible patients (Apr 2017)|
|Imvigor-211||2nd-line study, failed to show OS benefit vs chemo||Trial failed to confirm Tecentriq's 2nd-line benefit (May 2017)|
|Imvigor-130||1st-line study, OS for chemo beat Tecentriq in PD-L1-low subjects at interim||Interim analysis, led to 1st-line cisplatin-ineligible setting being limited to PD-L1 ≥5% patients (Jul 2018); those ineligible for any chemo still qualify regardless of PD-L1 status|
|1st-line study, positive for PFS at interim; OS immature||Data to be discussed with regulators while study continues to final OS readout (Aug 2019)|