ALTN-AK105-II-02 cohort 4: A phase II study of penpulimab plus anlotinib in patients (pts) with previously treated locally advanced or metastatic urothelial carcinoma (UC)

Immune checkpoint inhibitors (ICIs) have been approved for advanced/metastatic UC failed with platinum-based chemotherapy. Anti-angiogenesis agents has synergistic effect with ICIs. The safety and efficacy of penpulimab (a humanized anti-PD-1 IgG1 monoclonal antibody) in combination with anlotinib (a multi-target tyrosine kinase inhibitor of angiogenesis) in this patient population (cohort 4) was evaluated in a multicohort, open-label, phase 2 study ALTN-AK105-II-02. In cohort 4, eligible pts were aged 18 years or older with metastatic or unresectable locally advanced UC progressed after treatment with at least one chemotherapy regimen, measurable lesion (according to RECIST v1.1), and ECOG PS of 0 or 1. Pts received penpulimab 200 mg intravenously on day 1 and anlotinib 12 mg orally once daily on day 1 to 14 every 3 weeks until progression or intolerable toxicities. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Fifteen pts were enrolled from Sep 2020 to Apr 2022 with a median follow-up time of 9.8 months. The median age was 63 years (40-74), 66.7% were male, 33.3% were bladder cancers and 66.7% were primary tumors in the renal pelvis or ureter. The confirmed ORR was 33.3%. The DCR was 80.0%, with partial response and stable disease recorded in 5 (33.3%) and 7 (46.7%) pts. The median PFS was 6.8 months (95%CI 1.3-12.2). The median DOR was not reached, and the OS is currently immature. The most common TRAEs of any grade were hypertension (66.7%), hand-foot syndrome (46.7%), hypothyroidism, hyponatremia and proteinuria (40.0% each). Grade 3 TRAEs occurred in 6 (40%) pts, the most common of which was hypertension (20%). There was no grade 4-5 TRAEs. Penpulimab was discontinued in 1 (6.7%) pts for grade 3 myocarditis. Penpulimab plus anlotinib demonstrated promising anti-tumor activity with a manageable safety profile in pts with previously treated locally advanced or metastatic urothelial carcinoma.