Clinical efficacy of cabozantinib plus nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients (pts) with chemotherapy-refractory metastatic urothelial carcinoma (mUC) either naïve (n) or refractory (r) to checkpoint inhibitor (CPI).

Abstract

4528 Background: Preliminaryclinical activity of CaboNivo and CaboNivoIpi has been previously reported for mUC pts and other genitourinary tumors. Here, we report longer follow-up data of CaboNivo and CaboNivoIpi in pts with mUC nCPI and safety and preliminary clinical activity of CaboNivo in mUC rCPI Methods: This phase 1 dose + expansion cohorts study enrolled mUC nCPI (escalating doses of CaboNivo n = 15 and CaboNivoIpi n = 8) and mUC rCPI (Cabo40-Nivo3mg/kg n = 7) pts until progression/unacceptable toxicity. Objectives: Safety, ORR, DOR, PFS and OS. Tumors were assessed for response q8wks (RECIST 1.1). Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0. Results: 30 mUC pts enrolled. Median follow-up: whole cohort: 11.9 months; mUC rCPI: 5.6 months. All G clinical AEs in ≥20% (n = 29): fatigue (83%), diarrhea (72%) and anorexia (62%); laboratory AEs: ALT elevation (55%), AST elevation (48%) and hyponatremia (48%). Common ≥G3 clinical AEs: fatigue (17%), HTN (14%), thromboembolic events (14%); laboratory AEs: lipase elevation (31%), hypophosphatemia (17%), hyponatremia (10%). Immune-related AEs 14% (n = 4): mUC nCPI: CaboNivo: G3 meningitis; G3 pneumonitis; CaboNivoIpi: G3 colitis; mUC rCPI: G2 adrenal insufficiency. For mUC nCPI CaboNivo ORR: 50% (6/12), mDOR: 24.1months(mo) [95% CI: 7.8 mo-not reached (NR)]; mPFS 24.1mo [95% CI:1.6mo-NR] & mOS: NR. For mUC nCPI CaboNivoIpi: ORR: 33% (2/6), mDOR: NR; mPFS 10.1mo [95% CI:1.6 mo-NR] & mOS: NR. For mUC rCPI CaboNivo, ORR: 28% (2/7), SD 57% (4/7) and DOR: 100% at 5mo. Conclusions: Both CaboNivo and CaboNivoIpi are safe and active in mUC nCPI pts, CaboNivo is also active in mUC pts previously treated with immunotherapy, suggesting the addition of Cabo to Nivo may aid in overcoming CPI resistance. Clinical trial information: NCT02496208.