Search

794 Background: Tumor genomic testing (GT) has increased diagnostic accuracy and treatment options for patients (pts) with cancer. Dana-Farber Cancer Institute (DFCI) has made GT accessible as an institute-supported research effort for >10 yrs. We estimate 50% standard therapies and 15-35% clinical trials in Gastrointestinal Cancer Clinic (GCC) require GT to determine eligibility. Pts in GCC with certain cancers are eligible for GT as a clinical test – these include metastatic/locally advanced colorectal, gastric, pancreatic, or biliary cancers. Clinical testing requires CLIA lab certification and insurance reimbursement; research does not. Herein we ID gaps in our GT database. Methods: We reviewed data on GT uptake in GCC between 4/2015 - 6/2022. 20,096 pts were captured by the GT tracking system. Data included: testing ordered and completed (proportion, type, time to receiving tissue for testing [TR], time to testing completion [TC]). Demographic data is not captured in the tracking system; matching unique patient identifiers with electronic health record is pending. Results: Most pts received GT (57.6%); 12% were not eligible; 30.4% declined consent. Most testing was completed (67.6%), but 21.3% of tests failed (45.5% of these from insufficient tissue). Research testing (71%) comprised most tests, but clinical tests were completed faster (median 34 days research vs 20 days clinical). Ampullary (91%), anal (90%), colon (90%) had highest completion rates; pancreatic (59%), hepatocellular carcinoma (56%) had lowest (from insufficient viable tumor in submitted specimens). Conclusions: GCC has a robust recruitment program that has yielded high GT uptake. Given the frequency that GT is used for treatment and trials, building a demographically representative dataset is crucial, especially for pts with largest burden of morbidity and mortality from cancer. We ID'd data gaps in the GT tracking system, which lacks demographics and reason for not testing. Demographic data is available in the electronic health record but does not speak with the GT tracking system so this analysis is not routinely done. Ability to visualize this data is important to ensure equitable GT uptake. Future efforts will focus on improving rates of consent in genomics databases and cancer clinical trials. Genomic testing at Dana-Farber Cancer Institute Gastrointestinal Cancer Center, 4/2015 – 6/2022.[Table: see text]

119 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-strand breaks leading to cell death. In preclinical models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the safety and efficacy of radium-223 + olaparib. Tissue based studies investigated homologous recombination repair (HRR) gene status. Methods: This was an open-label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of radium-223 + olaparib. Eligible patients (pts) had mCRPC with ≥2 bone metastases without visceral metastases or lymphadenopathy > 4 cm. There was no limit on prior therapy. All pts had a baseline biopsy and archival tissue was collected when available. The phase 1 used a 3+3 dose escalation design with fixed dose radium-223 (55 kBq/kg IV every 4 weeks x 6). Dose level 1 (DL1) was olaparib 200 mg PO BID; DL2 was olaparib 300 mg PO BID. The primary objective was to determine the recommended phase 2 dose (RP2D). Secondary objectives included radiographic progression-free survival (rPFS) (PCWG3 criteria), PSA response (50% decline from baseline), and alkaline phosphatase response (30% decline from baseline). HRR gene status was determined using Oncopanel tissue profiling. Results: 12 pts were enrolled on the phase 1. Median age was 68 (range 59-81) years. Median prior lines of CRPC therapies was 2 (1-5), including 3 (25%) who had received prior chemotherapy and 12 (100%) a prior novel hormone therapy. The RP2D of olaparib was 200 mg BID when combined with radium-223. Overall, PSA response and alkaline phosphatase response were 16.7% (n=2) and 67% (n=8), respectively. Median follow-up was 6.5 (range 2.8, 11.8) months, and 6-month rPFS was 57% (95% CI: 25%, 80%). 9 patients had available tissue for Oncopanel testing (7 from baseline metastasis biopsy; 2 from archival prostate tissue). Two patients were identified to have pathogenic HRR gene alterations: 1 patient with a BRCA2 mutation with rPFS of 11.63 months, 1 patient with CDK12 mutation with rPFS 2.60 months (Table). Conclusions: We demonstrate that olaparib can be safety combined with radium-223 with RP2D of 200 mg BID. Though limited by sample size, we demonstrate prolonged disease control in a pt with a BRCA2 mutation receiving radium-223 + olaparib. Additional profiling from the currently accruing phase 2 study of radium-223 +/- olaparib will further elucidate biomarkers of response. Clinical trial information: NCT03317392. [Table: see text]