2H26 Catalyst Analysis: Zanza STELLAR-304 in nccRCC: Exelixis Inc. | North America

Research evidence excerpt

2H26 Catalyst Analysis: Zanza STELLAR-304 in nccRCC: Exelixis Inc. | North America

ecially in comorbid patients.

STELLAR‑304 represents a broad randomized Phase 3 evaluation of TKI+IO specifically in nccRCC, with results that could bring the

disease into the era of evidence-based combination therapy. KOLs often remark that nccRCC has had limited prior options, and a

positive STELLAR‑304 readout would give physicians and patients higher-quality evidence for a 1L regimen supported by randomized

pivotal data. In summary, the trial is expected to succeed vs. sunitinib; the crucial question is how high it raises the bar and whether the

regimen is safer and more tolerable to use than existing IO+TKI options.

Evaluating the Benchmark: Efficacy & Tolerability

Sunitinib remains the randomized comparator in STELLAR-304, but we think it represents a low-efficacy historical control and

statistical floor, rather than a meaningful modern clinical benchmark. While we see the control arm as the appropriate randomized

anchor, it does mean that historical sunitinib performance needs to be interpreted in the context of nccRCC biology and cross-trial

benchmarks. In PAPMET, sunitinib produced only 4% ORR and mPFS of ~5.6 months in papillary RCC; broader nccRCC data from ESPN

showed ORR of 9% and mPFS of 6.1 months; ASPEN demonstrated 18% ORR and mPFS of 8.3 months in mixed nccRCC; and SUPAP

reported papillary type 1/type 2 partial response rates of 13%/11% with mPFS of 6.6/5.5 months.

Taken together, we think these datasets support an expected sunitinib range of ~5-15% ORR and ~5-8 months mPFS in nccRCC. This

distinction matters because a statistically significant PFS win over sunitinib could still be clinically and commercially underwhelming if