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OBJECTIVE: To investigate if underrepresentation of racial and ethnic minorities exists in metastatic colorectal carcinoma (CRC) clinical trials. SUMMARY BACKGROUND DATA: Representation of vulnerable subpopulations is essential for generalizability of clinical trials. Limited studies to date have investigated racial and ethnic representation of patients enrolled in clinical trials for metastatic CRC. METHODS: ClinicalTrials.gov was queried for metastatic CRC clinical trials in the United States from 2000-2020. Incidence data were extracted from the SEER Database. Enrollment fraction (EF) was defined as number of trial participants divided by U.S. incidence of metastatic CRC in each race, ethnicity, and gender. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of U.S. metastatic CRC incidence for each subgroup. RESULTS: 8084 patients from 135 clinical trials were analyzed. 49.6% of clinical trials reported race data and 34.8% reported ethnicity data. Compared to 2000-2009, 2010-2019 had increased representation data reporting for race (61.2% vs. 38.8%) and ethnicity (64.6% vs. 35.4%). Of trials with race data, White patients represented 77.0%, Black patients 6.6%, Asian/Pacific Islander (API) patients 16.1%, American Indian/Alaska Native (AIAN) patients 0.2%, and Hispanic patients 6.8%. Black patients (median RQ 0.54), API patients (median RQ 0.19), AIAN patients (median RQ 0.00), and Hispanic patients (median RQ 0.26) were underrepresented. Black patients had a higher degree of underrepresentation in clinical trials with serum creatinine inclusion criteria (RQ 0.40 vs. 0.86, P=0.034). CONCLUSIONS: Strategies are needed to increase minority enrollment in clinical trials for metastatic CRC. Identification of systemic barriers is integral in public policy advocacy to increase representation.
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Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Methods: Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Discussion: Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. Trial Registration: ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.