Background: Cetrelimab (CET) is an investigational checkpoint inhibitor (CI). In part 1 of a first-in-human (FIH) trial (LUC1001; NCT02908906), pts with advanced solid tumors with ≥1 prior treatment received CET 80–800 mg Q2W or 480 mg Q4W. Response rates and safety profiles were similar to other CIs. Based on preclinical and clinical data, a phase 1/2 study (NORSE; NCT03473743) of CET + erdafitinib (ERD) in metastatic urothelial carcinoma (mUC) + FGFR alterations (alt) was initiated and is ongoing. Methods: In LUC1001 Part 2, pts with nonsmall cell lung cancer (NSCLC), melanoma (MEL), or MSI-H/dMMR colorectal cancer (CRC) received CET IV 240 q2w. Overall response rates (ORR = % complete response + partial response [PR] confirmed) were assessed as per RECIST v1.1. Adverse events (AEs) were assessed for all patients receiving CET IV 240 q2w in parts 1 and 2. Results: As of July 1, 2019, 122 pts with NSCLC (n=30); MEL (n=50); or CRC (n= 42) had been treated in Part 2. Median age ranged from 58 to 64 yrs (overall range, 23–86 yrs). Duration of treatment was 8.1 mos (range, 0.0-24.7) for NSCLC; 5.5 mos (range, 0.0-25.0) for MEL; and for 3.0 mos (0.0-16.1) for CRC. ORR was 37% in NSCLC; 53% in PD-L1+ NSCLC (≥50% by IHC), 28% in MEL; 32% in non-uveal MEL, 14% in CRC and 24% in centrally confirmed MSI-high CRC. In all CET IV 240 q2w treated pts in the FIH study (N= 162), treatment-related grade ≥3 and serious AEs were reported in 15% and 12% of pts, respectively. All grade and grade ≥3 immune-related (ir) AEs were reported in 41% and 8% of pts, respectively Most common ir AE: hypothyroidism (8%), asthenia (6%), diarrhea (4%), rash (4%), hyperthyroidism (4%), dyspnea (3%), pruritis (3%) and pneumonitis (3%). There was 1 treatment-related death due to myasthenia gravis. In the phase 1 combination study (NORSE), pts with mUC + FGFR alt (n=17) received fixed-dose CET IV 240 q2w + ERD 6mg, 8 mg or 8mg + up titration (UpT) to 9 mg to establish the RP2D for the combination as CET + ERD 8mg + UpT. In the RP2D group (n=10), 60% had treatment-related grade ≥3 AEs. ORR (all confirmed PR) was 50% in the all treated response-evaluable group (n=16). Conclusions: CET is a CI with efficacy and safety profiles in advanced solid tumors similar to approved CIs. In NORSE phase 1, CET+ ERD demonstrated antitumor activity in mUC with an acceptable safety profile. NORSE phase 2 is evaluating this combination as first-line therapy in pts with mUC with FGFR alt. References: Rutkowski, et al J Clin Oncol.2019; 37 (8 suppl): 31-31. Moreno, et al. ASCO-GU Genitourinary Cancers Symposium. February 13-15, 2020. San Francisco, CA. Clinical trial information: NCT02908906 and NCT03473743.