Background: Despite receiving identical standard-of-care therapies, epidemiological data indicate that Native American (NA) patients (pts) with cancer have worse outcomes vs. White pts. ICIs have revolutionized the treatment of certain tumors, however pts from certain racial and ethnic groups, including NA pts, are underrepresented in ICI trials. Methods: This is an ongoing multi-center retrospective study across four U.S. academic cancer centers that serve a high volume of NA pts. We included pts with self-reported race as NA in electronic medical records. We evaluated clinical outcomes and immune-related adverse events (irAEs) of 71 NA pts age ≥18 years with various solid tumors treated with ICI-based therapies between 2015 to 2021. IrAEs were defined based on the Common Terminology Criteria for Adverse Events (version 5.0) or RECIST 1.1. as available, was used to determine objective response rate (ORR). Kaplan Meier log-rank method was used to generate median progression free survival (mPFS) and median overall survival (mOS). Results: Median age (range) at ICI initiation was 62 (24 -81) years; 43 (60%) were males, with 26 (37%) females, 2 pts with missing gender data. 55 (77%) of pts had ECOG performance status 0. The distribution of top six tumor types included (number of pts [%]): non-small cell lung cancer (NSCLC) 22 (31%), renal cell carcinoma (RCC) 16 (23%), melanoma 7 (10%), small cell lung cancer (SCLC) 4 (6%), hepatocellular carcinoma 4(6%); colorectal adenocarcinoma, head and neck squamous cell carcinoma, cervical squamous cell carcinoma each had 3 pts (4%). Most pts (51 [72%]) received single agent ICI, 12 (17%) had dual ICI, 4 (6%) had chemotherapy+ ICI, and remaining had either ICI + tyrosine kinase inhibitor or ICI + study drug (4 [6%]). 55% of pts with NSCLC underwent tumor next-generation sequencing (NGS) while <30% of patients with renal cell carcinoma or melanoma had tumor NGS performed. Among 71 pts, 17 (24%) had any grade (G) irAE, 4 (6%) were reported to be ≥G3. The median time to irAE onset was 18 weeks and 3 (4%) pts discontinued ICI due to irAEs. The mPFS, mOS and ORR for the most frequent tumors (N ≥5) are shown. Conclusions: Although limited by sample size, our emerging data provides new insights into ICI efficacy and irAEs in NA pts that have been unknown to date. To our knowledge, this is the first and only attempt to date evaluating ICI outcomes in NA pts. Updated clinical data and tumor genomics will be presented at the meeting.