2.1.1. IMvigor210 Trial Cohort 2

On 18 May 2016, the FDA granted accelerated approval to atezolizumab, a PD-L1-targeting mAb, for use in patients with bladder cancer with locally advanced or metastatic bladder cancer who have disease progression during or following platinum-containing chemotherapy or within 12 months of receiving neoadjuvant or adjuvant platinum-containing chemotherapy [20]. Approval was based on this single-arm phase II trial. This cohort contained 310 patients with inoperable locally advanced or metastatic bladder cancer that had previously received cisplatin-containing chemotherapy [21]. Immunohistochemistry (IHC) staining evaluated the number of PD-L1-positive tumor-infiltrating immune cells (IC) and categorized patients into IC0, IC1, or IC2/3 groups. IC0, IC1, IC2, and IC3 scoring was proportional to tumors containing <1%, ≥1% and <5%, ≥5% and <10%, and ≥10% ICs within a given microscopic field of view, respectively. This PD-L1 scoring system was determined using

the diagnostic assay SP142 (Ventana Medical Systems Inc. Tucson, AZ, USA). The scoring method first identifies a defined tumor area that contains at least 50 viable tumor cells [22]. For example, a score of IC3 is given when a tumor tissue shows either ≥50% of tumor cells that stain for PD-L1 or ≥10% of the tumor area is occupied with ICs that stain for PD-L1 [22]. Thus, PD-L1 scoring can be determined solely by the percentage of tumor cells or ICs that express PD-L1 and a combined score is not taken into account. The scoring for atezolizumab in patients with bladder cancer was reliant on ICs and not on tumor cells [21].

At the initial follow-up time of 11.7 months, the ORRs were 26% (95% CI, 18–36%) in the IC2/3 group, 18% (95% CI, 13–24%) in the IC1 and IC2/3 combined group, and 15% (95% CI, 11–19%) in all patients [21]. There were ongoing responses in 85% of responding patients and the median DOR was not reached (2.0–13.7 months). The median OS was 11.4 months (95% CI, 9.0—not reached) in the IC2/3 group, 8.8 months (95% CI, 7.1–10.6) for the combined IC1 and IC2/3 groups, and 7.9 months (95%, 6.6–9.3) in all patients. At the median follow-up of 33 months, the median ORR, OS, and DOR were 16%, 7.9 months, and 24.8 months (Table 1).


**Table 1.** Updated clinical trial ORR, OS, and DOR for ICIs and targeted agents as monotherapies.

ICIs = Immune checkpoint inhibitor; ADCs = Antibody-drug conjugates; ORR = Objective response rate; OS = Median overall survival; DOR = Median duration of response; NR = Not reached. <sup>1</sup> For first-line treatment (cisplatin-ineligible). <sup>2</sup> For second-line treatment. <sup>3</sup> For first-line treatment (cisplatin-eligible). <sup>4</sup> Patient population included those who had previously received ICI therapy. <sup>5</sup> Not approved. Has been granted fast track designation by the FDA. <sup>6</sup> For patients with prespecified *FGFR* alterations.
