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e16242 Background: Pancreatic cancer (PC) is a highly fatal disease, and multiple studies have shown that African Americans (AA) have a higher incidence of PC compared with Whites and have a higher risk of PC-related mortality. Differences in known risk factors for PC including cigarette smoking, obesity, diabetes and family history have been demonstrated to not fully account for the racial disparity in incidence. Furthermore, differing mortality rates by race are not entirely attributable to variables such as access to care and disparate management. Whether there are molecular and biologic differences in PC that could explain these disparities is a question that has important scientific and clinical consequences. Unfortunately, most large studies of genomic alterations in PC include very few AA patients (pts). This study tries to characterize molecular alterations seen in AA pts with PC. Methods: The electronic medical record was queried for all self-identified Black or AA pts who were diagnosed with PC and had molecular profiling from November 2015 to November 2021. Patient demographics, clinical characteristics and molecular genomics were analyzed. The primary outcome was percent of patients with specific KRAS mutations. The secondary outcome was differences in KRAS mutations by gender. Results: We identified 50 AA pts with PC who underwent molecular profiling, 19 of whom (38%) were female. As expected, most (66%) were advanced stage at diagnosis. 32 pts (64%) had tissue-based molecular profiling with 18 (36%) having blood-based testing. A KRAS mutation was identified in 38 pts (76%). 15 (30%), 12 (24%), and 11 (22%) had G12V, G12D, and G12R mutations in KRAS, respectively. Men were more likely to have a G12D mutation (35.5% vs 5.3%, P = 0.018), and women were more likely to have a G12V mutation (47.4% vs 19.4%, P = 0.036). There was no significant difference in overall survival between men and women. 30 pts (60%) had additional mutations other than KRAS. 6 pts (12%) did not have a KRAS mutation detected despite the presence of other alterations. 4 pts had no mutations detected on molecular next generation sequencing, 3 of which had blood-based testing. Conclusions: In our review of genomic mutations of AA pts with PC, KRAS G12V mutations were most common. Only 24% of our studied population had KRAS G12D mutations. The frequency of specific KRAS mutations differs from what has been described in the literature among predominantly White pts with PC, where almost half of pts have a G12D mutation and 28% and 17% harbor G12V and G12R mutations, respectively. Two major limitations of this study are the small sample size which limits definitive comparisons between races, and the imperfect sensitivity of molecular profiling. KRAS is thought to be present in > 90% of PC, but the mutation was only identified in 76% of our pts. Further studies should be conducted to determine whether different molecular characteristics could account for racial disparities in PC mortality.

3059 Background: CBP501 is a 12-amino acid G2 checkpoint abrogator and calmodulin-modulating peptide that increases platinum influx into tumor cells and induces tumor immunogenic cell death. CBP501 also suppresses platinum-induced release of cytokines by macrophages, lowers cancer stem cell populations, and reduces migration, invasion, and epithelial-mesenchymal transition of tumor cells. We report safety and efficacy outcomes from dose-escalation and expansion cohorts of a Phase Ib study of CBP501 combined with cisplatin and nivolumab (NCT03113188). Methods: An open-label Phase I trial was conducted using a 3+3 design: CBP501 and cisplatin were dosed simultaneously by 1h infusion Q3W at 4 different combined dose levels (CBP501: 16 or 25 mg/m2; cisplatin: 60 or 75 mg/m2) in the dose-escalation cohort. Nivolumab (240 mg) was dosed on the same day as a 1h infusion following CBP501/cisplatin. CBP501 and cisplatin were fixed at 25 and 60 mg/m2, respectively, in the expansion cohort. Eligible patients had pathologically confirmed, locally advanced or metastatic solid tumors, age ≥18 years, ECOG PS 0-1, life expectancy > 3 months. The dose-expansion cohort had pretreated metastatic exocrine pancreatic cancer or microsatellite stable colorectal cancer (CRC). Scans were performed every 6 weeks while on study, then every 3 months. Results: The most common related adverse events (AEs) were infusion-related reaction (rash, itching, hives; n = 32/37 [Gr 1, n = 4; Gr 2, n = 28]; 86%) and anemia (n = 19/37 [Gr 1/2, n = 10; Gr 3, n = 9]; 51%). There were no additional safety signals other than those known for each agent. At January 9, 2020 (interim analysis), efficacy was evaluable in 17/19 patients in the dose-escalation cohort. Unconfirmed partial response was seen in 18% (3/17; 1 pancreatic, 1 colorectal, 1 cholangiocarcinoma), with > 3 months stable disease (SD) in 41% (7/17), disease control in 41% (7/17), and > 8 months overall survival (OS) in 53% (9/17). In the expansion cohort, efficacy was evaluable in 8/13 patients with pancreatic cancer: > 4 months SD was 50% (4/8), median progression-free survival 4.2 months, and median OS 5.9 months (6/8 ≥3rd line). The CRC cohort median OS for all CRC patients (n = 10) including the dose-escalation cohort (n = 5) was 17.5 months (10/10 ≥3rd line). Conclusions: The triple-drug combination is reasonably tolerable with preliminary signs of efficacy in refractory solid tumors, including those in which cisplatin and nivolumab have limited single-agent activity. Clinical trial information: NCT03113188 .

410 Background: Recent advances in front-line therapy have improved survival in patients with advanced PDAC. A fluorouracil-based regimen is recommended for patients who progress on a gemcitabine-based therapy. Tosedostat is an oral aminopeptidase inhibitor that disrupts the cleavage of amino acids from peptides downstream of proteasomal degradation. It prevents the recycling of free amino acids, leads to intracellular depletion of amino acids, and triggers an amino acid deprivation response that subsequently results in apoptosis. Because PDAC cells frequently upregulate expression of these aminopeptidases, tosedostat offers therapeutic promise, particularly in combination with fluoropyrimidines. Methods: This is a single institution phase I/II trial to evaluate the safety and toxicity of tosedostat plus capecitabine in patients with metastatic PDAC progressed on a gemcitabine-based therapy. The phase I portion is being conducted in a dose de-escalation fashion, with two dose levels of tosedostat (120 mg or 60 mg) p.o. daily on days 1 to 21 with capecitabine 1000 mg/m2 p.o. BID on days 1 to 14 of a 21-day cycle. If more than one out of 6 patients in the tosedostat (120 mg) cohort experience a dose limiting toxicity (DLT), then 6 more will be enrolled to the tosedostat (60 mg) cohort. The primary objective of the phase I portion is to determine the optimal phase II dose. The primary objective of the phase II portion is to determine the progression-free survival at 3 months. Secondary objectives include the overall response rate, overall survival and CA 19-9 response. To avoid futility, interim analysis is planned after 10 evaluable patients enrolled. Results: Up to date, a total of 11 patients have been enrolled in the study, and 10 patients are evaluable. No DLT have been observed. Tosedostat at a dose of 120 mg with capecitabine is extremely well tolerated. Prolonged stable disease has been observed in 4 (40%) patients with a time on treatment of 10 months, 7.5 months, 5.5 months and 4 months, and 3 of the 4 patients remain on the trial. Conclusions: The combination of tosedostat and capecitabine is a well-tolerated regimen with impressive clinical activity in the subset of patients studied thus far. Clinical trial information: NCT02352831.

11523Background: Somatic mutations in mismatch repair (MMR) genes MLH1, MLH3, MSH2, MSH3, MSH6, and PMS2, and/or DNA polymerase POLE, are associated with a high mutation burden in cancer genomes. H...

8536Background: Pulmonary large cell neuroendocrine carcinoma (LNEC) is an uncommon lung cancer subtype, initially described in 1991 and classified as a high grade neuroendocrine tumor. Since the d...

e19043 Background: Pemetrexed (Pem) has been widely used in non-small cell lung cancer (NSCLC), but data of biomarkers predicting its clinical response and outcome is very limited. Thymidylate synt...

e12515 Background: The incidence of LC in patients (pts) with LTx is higher than general population. Treatment (trmt) remains controversial given the immunosuppressive state and comorbidities. The ...

637 Background: Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) is frequently used for prognosis for BCBM. We evaluated DS-GPA plus other potential prognostic factors for overall survival ...

2090 Background: Pts with SCLC commonly develop BM and the GPA is frequently used as a prognostic index for overall survival (OS). GPA includes 4 groups (GPA scores 0-1.0 (worst), 1.5-2.0, 2.5-3.0,...

8116 Background: NSCLC is the most common cause of BM and GPA is used as a prognostic index (PI) for BM. We evaluated its validity in a contemporary large cohort treated at a single tertiary care institution. Preliminary data was presented at ASCO 2013. Methods: IRB approved. NSCLC BM treated between 2000 and 2012 was identified from the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database. OS from the diagnosis of NSCLC BM was the primary end point.Cox proportional hazards models were used for data analysis. Results: 958 (54% male) patients were included for final analysis. Median age at BM diagnosis was 62 years (29-92). Karnofsky performance scale (KPS) was 90-100 in 345 (39%), 70-80 in 415 (47%) and 5 in 136 (14%) patients. Initial therapy included stereotactic radiosurgery (SRS) in 186 (20%) patients, whole brain radiation (WBRT) in 420 (44%), surgery (S...

e19025 Background: Pemetrexed (Pem) is the first agent showing different efficacy based on histology in the treatment (tx) of NSCLC. Our goal was to identify outcome predictors in patients (pts) with metastatic NSCLC (mNSCLC) treated with pem. Methods: Retrospective data of pts with mNSCLC who received pem were analyzed. Variables included demographics, ECOG performance status (PS), disease sites, pre/post-pem tx, and toxicities. Clinical benefit defined as complete response (CR), partial response (PR), and stable disease (SD) >6 months, progression-free survival (PFS), and overall survival (OS) were analyzed using logistic regression and Cox proportional hazards model. Results: 240 pts were included. 55% male, 84% smokers. 68% adenocarcinomas, 10% squamous/adenosquamous carcinomas. Median age 64 years (range 34-84). Pem was given for a median of 4 cycles (range 1-73), as 1st line in 20% and 2nd line in 50%, given as a single agent in 69%. The most common toxicities were constitutional (50%) and GI related (29%). 31% of pts achieved CR (n=4) or PR, 33% progressed, 36% had SD. Front-line pem use (p=.0003), adenocarcinoma histology (p=.05), and non-pulmonic metastatic sites ≤2 (p=.01) were independent predictors of clinical benefit, with response rate of 71% for pts with all three features, compared to only 7% for pts with none of these features. Multivariable analysis of survival data revealed ECOG PS >1, non-pulmonic metastatic sites>2, and squamous/poorly differentiated histology predicted poor PFS and OS. In addition, interval from diagnosis to start of pem 2 non-pulmonic metastatic sites, squamous/poorly differentiated histology predict poor PFS and OS. An analysis of biomarkers is ongoing.

e15537 Background: The GPA is a commonly used prognostic index based on RTOG protocols in patients with brain metastases (BM). The purpose of this study was to evaluate the utility of GPA index in a contemporary cohort of renal cell carcinoma with brain metastases (RCCBM) at a larger tertiary care center to predict overall survival. Methods: IRB approval was obtained and the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify RCCBM patients (pts) treated in the recent era (2000-12). A proportional hazards model was used to assess OS, which was measured from the date of diagnosis of brain metastases to death or last follow-up. Results: 136 RCCBM (100 males), median age 60 years (range 32-79), were evaluated. Pts had a median of 2 (range 1-15) BM; Karnofsky Performance Scale (KPS) was 90-100 in 57%, 70-80 in 38% and 3).GPA was not prognostic for survival (p=.40), and neither GPA coding of KPS nor BM (1, 2-3, >3) was associated with outcome (p=.90 and .26, respectively). In contrast, diagnosis of RCC to BM >5 years, p=.004, brain as an initial site of metastasis, p=.005, normal hemoglobin, p=.01, a single BM, p=.02, controlled primary, p=.02, and age≤65 were found to be independently prognostic for improved OS. Using these factors, an alternative index can be formed. Conclusions: RCCBM specific GPA was notprognostic for OS in this study (p=.40), however a new index was developed based on a revised set of independent prognostic factors that was significant (p

e19012 Background: Bev in combination with chemotherapy (CT) is a standard treatment for pts with stage IV NSCLC. However, there are no established biomarkers to improve benefit-to-risk profile of therapy. CEC are a marker of vascular turnover. We hypothesized CEC may be associated with treatment outcome/toxicity. Methods: Stage IV NSCLC pts were treated with Bev along with CT of choice per clinician. CEC were measured at baseline and after 2 cycles of Bev-containing therapy. CellSearch (Veridex, New Jersey) was used to capture and quantify CEC via immunomagnetic and immunofluorescence techniques. CEC were enumerated as nucleated, CD146+/CD105+/CD45- cells in 4 mL of blood. For comparison, baseline CEC were also collected in 3 other groups; healthy subjects, stage I-III NSCLC, and advanced solid tumor pts. Chi-square tests and non-parametric methods were used to assess associations between CEC and pt/disease characteristics, toxicity, and proportional hazards models were used for comparisons of progression free and overall survival (PFS and OS). Results: Evaluated were 62 individuals: 29 stage IV NSCLC, 10 stage I-III NSCLC, 13 advanced solid tumors (melanoma, sarcoma, renal and adrenal cancers), and 10 healthy subjects. The median of CEC/ml blood in healthy subjects was 6. Based on its distribution, CEC >13/ml was deemed elevated. Elevated CEC was seen in 48% of stage IV NSCLC (median 12/ml), in comparison to 20% of stage I-III NSCLC (8/ml) and 23% of advanced solid tumors (6/ml) Baseline CEC in stage IV NSCLC was independent of patient/ disease characteristics including site of disease and tumor size. CEC increased during treatment in most patients (61%). CEC doubling between baseline and cycle2 was associated with more cytopenia and hemorrhage. (75% vs 20%, p=0.05 and p=0.03 for absolute and relative CEC changes). Baseline CEC and changes during treatment did not correlate with response (p≥ 0.32) and pts with elevated baseline CEC had a trend towards worse PFS (p=0.09) and OS (p=0.10). Conclusions: CEC are commonly elevated in advanced NSCLC. CEC increases may be predictive of adverse events from Bev-CT and when elevated at baseline may suggest worse PFS.