Efficacy and safety of second-line cabozantinib ± atezolizumab for patients with advanced renal cell carcinoma after progression on immuno-oncology combinations: Subgroup analysis of CONTACT-03.

4523 Background: Cabozantinib (cabo), a vascular endothelial growth factor receptor-associated tyrosine kinase inhibitor (TKI), is a preferred treatment option for second-line (2L) treatment of advanced renal cell carcinoma (RCC) based on its superior efficacy vs everolimus (Choueiri TK, N Engl J Med 2015); however, its activity after contemporary first-line (1L) immuno-oncology (IO) combinations is not well characterized. CONTACT-03 was a large phase 3 study evaluating the efficacy and safety of cabo ± atezolizumab (atezo) after progression on previous IO treatment (Pal SK, Lancet 2023). We report the results of a subgroup analysis of the safety and efficacy of 2L cabo ± atezo in patients from CONTACT-03 who received standard of care (SOC) 1L IO-IO or IO-TKI combinations. Methods: In CONTACT-03, adults with metastatic RCC whose disease had progressed on IO-based regimens were randomized to cabo (60 mg PO QD) alone or with atezo (1200 mg IV Q3W). This subgroup analysis included patients who had received 1L IO-IO or IO-TKI SOC combinations prior to enrolling in CONTACT-3. Outcomes for 2L treatment included PFS by blinded independent central review (BICR), OS, ORR, duration of response, and safety. Results: Of 522 patients, 107 in the cabo arm and 129 in the cabo + atezo arm had received prior treatment with IO-IO (ipilimumab-nivolumab) or IO-TKI (axitinib-avelumab, axitinib-pembrolizumab, or lenvatinib-pembrolizumab). Efficacy outcomes were comparable between treatments (Table). For cabo and cabo + atezo, respectively, median PFS by BICR was 10.3 and 10.2 months, and ORR was 36% and 37%. Grade 3/4 treatment-related adverse events (AEs) were reported in 48% and 58% of patients treated with cabo and cabo + atezo, respectively, treatment-related serious AEs were reported in 13% and 25% of patients, and AEs led to dose modification in 87% and 92% of patients and discontinuation in 5% and 17% of patients, respectively. Conclusions: Results from this post-hoc subgroup analysis of CONTACT-03 suggest 2L cabo is effective in patients with advanced RCC previously treated with 1L IO-IO or IO-TKI regimens. Safety was consistent with the overall study. These results can inform clinicians making 2L treatment decisions for patients who have progressed on contemporary 1L IO-containing combinations. Clinical trial information: NCT04338269 . Efficacy outcomes with cabo ± atezo after 1L IO combinations. Cabo (n=107) Cabo + atezo (n=129) Median PFS by BICR, months (95% CI) 10.3 (7.95, 12.45) 10.2 (8.34, 10.64) Median OS, months (95% CI) NE (18.30, NE) 24.2 (20.24, NE) Best overall response by BICR, % 36 37 Complete response, % 0 0 Partial response, % 36 37 Stable disease, % 50 52 Progressive disease, % 10 5 Not evaluable/missing, % 5 6 Duration of response by BICR, months (95% CI) 15.0 (10.28, NE) 10.5 (7.95, NE) NE, not estimable.