Kasi, Anup

3623 Background: Minimal residual disease (MRD) assessment may effectively detect cure in patients with colorectal cancer (CRC). Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for MRD in patients. Recent studies have shown the ability to detect MRD using ctDNA assay to assess recurrence risk and patient selection for adjuvant chemotherapy. We performed a systematic review and metanalysis of post operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative intent resection with or without adjuvant chemotherapy. Methods: We searched PubMed/Medline, EMBASE, Web of Science, Cochrane Library, and Google from inception to February 3, 2022 using keywords related to colorectal cancer, ctDNA, and MRD. The search also includes paper and conference presentations. The search resulted in 427 studies after removing the duplicates. Data were extracted to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results: After the initial abstract screening, 48 studies were identified. The final review led to the inclusion of 27 studies representing 3459 patients with evaluable ctDNA, with 623 having +ve post-surgery ctDNA levels. Seven studies had analyses of patients specifically with oligometastatic disease, the rest 20 studies subdivided within stages I-III. The pooled HR for RFS in post-surgical ctDNA +ve vs -ve patients in all stages was 7.16 (95% CI 6.12-8.36) p <0.00001. Subgroup analysis revealed pooled HR = 8.27 (95% CI 6.16-11.09) and 6.07 (95% CI 4.54-8.13) for stage I-III and IV CRC, respectively. Only 11 studies did analysis for post adjuvant chemotherapy patients based on ctDNA status. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA +ve versus -ve patients in all stages was 12.40 (95% CI 9.24-16.64) p <0.00001. Subgroup analysis revealed pooled HR = 13.95 (95% CI 9.08-21.43) and 11.39 (95% CI 5.99-21.66) for stage I-III and IV CRC, respectively. Conclusions: This is the largest and most current meta-analysis done on ctDNA levels as MRD assessment in CRC. Our analysis emphasizes that post operative ctDNA is a strong prognostic marker of RFS. Based on our results ctDNA can be a significant and independent predictor of RFS. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer. [Table: see text]

100 Background: CRC is a common cancer world-wide, accounting for ̃10% of cancer cases and mortality. Treatment options are limited, and survival is poor for pts with advanced disease, particularly those with mKRAS. After failure of 1L treatment for mCRC, regardless of KRAS mutation status, the ORR for FOLFIRI-bev is 5-13%, with PFS 4-6 mos, and OS 10-12 mos. Onvansertib is a highly selective, ATP-competitive, orally bioavailable PLK1 inhibitor that is synergistic with irinotecan and with 5FU in xenograft models of mKRAS CRC. We present preliminary safety, efficacy, and biomarker data from an ongoing Ph1b/2 trial of onvansertib + FOLFIRI-bev in pts with mKRAS mCRC progressing after 1L treatment with fluoropyrimidine + oxaliplatin, +/- bev. Methods: Pts with mCRC with a KRAS mutation detected by a CLIA-certified lab were eligible. In the Ph1b portion of the study, onvansertib was given on a 3+3 dose escalation at 12, 15 or 18 mg/m2 on days 1-5 and 15-19 of each 28-day cycle in combination with FOLFIRI-bev. The MTD was 15 mg/m2 and was chosen as the RP2D. The primary endpoint for the Ph2 was ORR, and radiographic response was assessed every 8 wks per RECIST v1.1. Safety was evaluated continuously, and AEs were recorded using CTCAE v5.0. Baseline and post-treatment blood samples were collected for biomarker analyses, including mutant allele frequency (MAF) of the pt’s known KRAS mutation. Results: As of 16Sep2021, a total of 50 pts had been treated: 18 on the Ph1b and 32 on the Ph2, including 35 pts at the RP2D, and median follow up was 4.7 mos (range 0.4-18). Of the 50 pts, 26 remain on treatment, as do 24 of 35 RP2D pts. The combination was well-tolerated: fatigue, neutropenia, and nausea were the most common treatment-emergent adverse events (TEAE) and were generally low-grade. Neutropenia was managed by removing the 5FU bolus from subsequent cycles of FOLFIRI and adding growth factor. Of the 50 pts, 44 were evaluable for efficacy, including 31 of 35 RP2D pts. ORR was 36% for the total group (1CR and 15 PR in 44 pts) and 35% for the RP2D group (1 CR and 10 PR in 31 pts). First responses were seen between 2 and 6 months after the start of therapy. Responses were observed across different KRAS variants. Pts achieving a CR or PR showed the greatest decreases in plasma MAF after the first cycle of therapy. Of the 50 pts, 24 pts have discontinued for the following reasons: progressive disease (13), toxicity (4), patient decision (4), proceeding to potentially curative surgery or other localized therapy (3). Conclusions: The combination of onvansertib with FOLFIRI-bev was well tolerated: observed TEAEs have been generally low-grade and manageable. The combination has demonstrated a promising ORR in 2L treatment of mCRC pts harboring various KRAS mutations, and efficacy was correlated with early changes in plasma mKRAS. Updated safety, efficacy, and biomarker analyses will be presented. Clinical trial information: NCT03829410.

11523 Background: Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes. Methods: The COVID-19 and Cancer Consortium (NCT04354701) is an international registry of pts with cancer and COVID-19. Adult pts (≥18 years old) with a diagnosis of sarcoma and laboratory confirmed SARS-CoV-2 were included from 50 participating institutions. Data including demographics, sarcoma diagnosis and treatment, and course of COVID-19 infection were analyzed. Primary outcome was the composite rate of hospitalization or death at 30 days from COVID-19 diagnosis. Secondary outcomes were 30 day all-cause mortality, rate of hospitalization, O2 need, and ICU admission. Descriptive statistics and univariate Fisher tests are reported. Results: From March 17, 2020 to February 6, 2021, N=204 pts were included. Median follow up was 42 days. Median age was 58 years (IQR 43-67). 97 (48%) were male. 30 (15%) had ECOG performance status ≥2. 104 (51%) received cancer treatment, including surgery or radiation, within 3 months of COVID-19 diagnosis. 153 (75%) had active cancer, of whom 34 (22%) had lung metastases. 100 (49%) pts met the composite primary endpoint; 96 (47%) were hospitalized and 18 (9%) died within 30 days from COVID-19 diagnosis. 64 (31%) required oxygen, and 16 (8%) required ICU admission. Primary endpoint rates were similar for pts who received cytotoxic chemotherapy (38/58, 66%) or targeted therapy (16/28, 57%). Pts with higher rates of the primary endpoint included patients ≥60 years old (59% vs 40%, OR 2.04, 95% CI 1.12-3.74, p=0.016), pts with ECOG PS ≥2 vs 0-1 (90% vs 41%, OR 12.2, 95% CI 3.44-66.8, p<0.001), pts receiving any systemic therapy within 3 months of COVID-19 diagnosis (62% vs 39%, OR 2.65, 95% CI 1.43-4.97, p=0.001), and pts with lung metastases (68% vs 42%, OR 2.77, 95% CI 1.19-6.79, p=0.013). Primary endpoint rates were similar across sarcoma subtypes (Table). Conclusions: This is the largest cohort study of pts with sarcoma and COVID-19 to date. Sarcoma pts have high rates of complications from COVID-19. Older patients, those with poor performance status, those recently receiving systemic cancer therapy, and those with lung metastases appear to have worse outcomes.[Table: see text]