Ph. 3 PIVOT-006 Preview Refresher & Investor Debates As We Await the Data

Research evidence excerpt

Ph. 3 PIVOT-006 Preview Refresher & Investor Debates As We Await the Data

: (i) SWOG S0337

enrolled LG patients which included both LR and IR, and (ii) ATLAS enrolled LG-IR patients

only, allowed for TURBT at 3mo for residual disease, and as mentioned, did not allow for

perioperative chemo. While CGON has been citing ATLAS as an imperfect but potentially more

relevant comp in recent months given its more recent completion, investors continue to debate

how PIVOT-006's inclusion of perioperative chemo may impact performance of the PIVOT-006

control arm i.e. where SWOG S0337 can shed more light, as the PIVOT-006 control arm may

reflect a blend of efficacy seen in both arms of the SWOG S0337 trial: ~15% 1-year recurrence

for those who received gem and ~30% 1-year recurrence for those who received saline.

Investors continue to debate what effect size in PIVOT-006 is clinically meaningful in

light of (1) the surveillance control arm, (2) the inclusion of HG-IR patients, (3) likely

comparisons to intravesical chemo despite its infrequent use, and (4) the potential

cost / logistics of creto. CGON has noted that a 30% relative risk reduction would be

clinically meaningful, in their view. Based on our discussions, we think investors seem to think

a HR=0.70 against a surveillance-based control arm may not be enough to warrant substantial

uptake in the IR-NMIBC setting given imperfect references to SWOG S0337 wherein a single

dose of gemcitabine showed 0.66 HR in ITT patients, and an even stronger 0.53 HR in all

patients that actually received a single gem instillation (both on a 4-year endpoint). Skeptics

point to these datapoints taken together with low overall utilization of intravesicle chemo in IR-

NMIBC patients as factors that raise the bar for incoming agents.