Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials

An anti-PD-1 antibody (SCT-I10A) plus anti-EGFR antibody (SCT200) and chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer: A phase Ib study.

A Phase 3 Open-Label, Randomized, Multicenter Study of Imprime Pgg in Combination with Cetuximab in Patients with Kras Wild Type Metastatic Colorectal Cancer

TPS787 Background: Imprime PGG (Imprime) is a novel immune modulator (complex carbohydrate biologic), which harnesses innate immune cells to enhance killing of antibody-targeted tumor cells. In a phase 2 single-arm clinical trial in mCRC, the combination of Imprime with cetuximab resulted in 24% ORR, 62% disease control rate (DCR), and median time to progression (TTP) of 12 wks (Tamayo ME, Ann Onc 2010), representing approximate 100% increases vs historical control (Cunningham, NEJM 2004). ORR was 45%, DCR, 82% and TTP, 24 wks in pts with KRAS WT tumors (post hoc analysis). Single-agent cetuximab has been shown to improve objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients (pts) with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type (WT) metastatic colorectal cancer (mCRC) who failed oxaliplatin- and irinotecan-based therapy or are intolerant to irinotecan. The mechanism of action of cetuximab is thought to rely on competitive blockade of endogenous ligand binding and downstream signaling, internalization and down regulation of EGFR, as well as antibody-dependent cellular cytotoxicity (ADCC) (Erbitux SmPC). The current trial, sponsored by Biothera (registered with ClinicalTrials.gov NCT01309126) is to confirm these findings in phase 3. Methods: Eligible pts will have had prior oxaliplatin- and irinotecan-based therapy or be intolerant to irinotecan, and will meet key inclusion criteria including measurable disease and ECOG performance status of 0 or 1. In a 2:1 randomization, stratified by geographic region, prior chemotherapy and site, approximately 795 pts will receive weekly open-label Imprime plus cetuximab or cetuximab alone. The primary endpoint of the study is OS and primary analysis will occur when ~709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses. Pt screening and enrollment is underway in the United States and Europe. Clinical trial information: NCT01309126.

3594 Background: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type Ras, however, only partial patients respond to cetuximab treatment. The effect of human epidermal growth factor receptor 2 (HER2) protein overexpression and Her2 gene mutant on the efficacy of cetuximab treatment was not well elucidated in patients with Ras wild-type unresectable mCRC. Methods: From June 2008 to December 2014, we identified 216 patients with Ras wild-type unresectable liver-limited mCRC base on our previous study (ClinicalTrials: NCT01564810.), whose Her2 gene mutation was analyzed by next-generation sequencing for single nucleotide polymorphism (SNP) of Her2 gene and HER2 protein overexpression was determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Results: Of these 216 patients, 103 were received cetuximab plus chemotherapy (cetuxima group) and 113 were received chemotherapy alone (chemotherapy group). The total rate of HER2 overexpression was 8.8%, including 9.7% in cetuximab group and 7.9% in chemotherapy group. HER2 overexpression caused impaired survival compared with HER2 non-overexpression patients in cetuxima group, with a median progression-free survival (PFS) of 4 months (95% CI 2.482-5.518) versus 10 months (95% CI 8.963-11.037; P< 0.0001), and a median overall survival (OS) of 15 months (95% CI 7.5-22.2) versus 36 months (95% CI 31.4-40.5) ( P< 0.0001). While, HER2 overexpression had no effect on treatment efficacy in chemotherapy group, when compared with HER2 non-overexpression paitents, with a median PFS of 5 months (95% CI 2.228-7.772) versus 5 months (95% CI 4.004-5.996; P= 0.615), and a median OS of 21 months (95% CI 6.975-35.025) versus 21 months (95% CI 17.772-24.228; P= 0.629). Meanwhile, we observed 25.5% of total Her2 mutant (24.2% in cetuximab group and 26.5% in cetuximab group), among of them 5 patients are HER2 overexpression. Total Her2 mutation has no impact on survival compared with Her2 wild-type ones in neither cetuximab group nor chemotherapy group. In further bioinformatics analysis is underdoing, and which subgroup or type of Her2 mutant potential affect cetuximab treatment need confirm. Conclusions: We show HER2 overexpression rather than total Her2 mutant contribute to resistance of cetuximab treatment in patients with mCRC harboring wild-type Ras. Next, the subgroup mutant in total Her2 mutant needs further analysis to confirm their roles in survival after cetuximab treatment.

The epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (MoAbs) have already shown the therapeutic effectiveness in patients with metastatic colorectal cancer (mCRC). But many patients resist to the treatment. The aim of this meta-analysis was to assess EGFR gene copy number (GCN) as a candidate predictive biomarker for resistance to anti-EGFR MoAbs in mCRC treatment. Systematic computerized searches of the PubMed, EMBase and Cochrane Library were performed. The primary endpoint was objective response rate (ORR). The second endpoints included progression-free survival (PFS), and overall survival (OS). The pooled odd ratio (OR) and pooled sensitivity, specificity, and summary receiver operator characteristic (SROC) for ORR were estimated. The pooled hazard ratios (HR) for PFS and OS were also calculated. Fourteen studies with 1,021 patients were included. Increased EGFR GCN was associated with increased ORR (OR=6.905; 95% CI: 4.489-10.620). It was also found in wild-type KRAS mCRC patients, with the pooled OR of 8.133 (95% CI: 4.316-15.326). GCN has medium value for predicting ORR, with the pooled sensitivity of 0.79 (95% CI: 0.73-0.84), the pooled specificity of 0.59 (95% CI: 0.55-0.62). In wild-type KRAS mCRC patients, the sensitivity and the specificity were 0.80 (95% CI: 0.70-0.87) and 0.60 (95% CI: 0.53-0.66), respectively. Increased EGFR GCN was associated with increased PFS (HR=0.557; 95% CI: 0.382-0.732) and OS (HR=0.579; 95% CI: 0.422-0.737). This meta-analysis suggests that EGFR GCN represents a predictive biomarker for tumor response in mCRC patients treated with MoAbs regardless of KRAS mutation. mCRC patients with increased EGFR GCN are more likely to have a better response, PFS, and OS when treated with cetuximab or panitumumab.

Cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Despite this established approach, cetuximab β (CMAB009), as a modified antibody of cetuximab, prospectively selected for dual RAS/BRAF wild-type patients, has not yet been validated in the Chinese mCRC patients through phase 3 trial. In this study (ClinicalTrials.gov identifier: NCT03206151), patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximab β plus FOLFIRI or FOLFIRI alone. The primary endpoint was blinded independent review committee-assessed progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgery rate for metastasis and R0 resection rate, and safety. From January 4, 2018 to September 2, 2021, a total of 505 eligible patients were enrolled and received study treatment; the median follow-up duration was 8.7 months (95% confidence interval [CI], 7.77 to 9.29) and 5.9 months (95% CI, 5.63 to 6.65) in cetuximab β plus FOLFIRI group and FOLFIRI group, respectively. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI demonstrated statistically significant improvements in median PFS (13.1 vs. 9.6 months, hazard ratio [HR], 0.639; 95% CI, 0.468 to 0.872; P = 0.004), median OS (28.3 vs. 23.1 months, HR, 0.729; 95% CI, 0.551 to 0.965; P = 0.024), and ORR (69.1% vs. 42.3%, odds ratio, 3.090; 95% CI, 2.280 to 4.189; P < 0.001). Cetuximab β plus FOLFIRI exhibited manageable toxicity without novel safety signals. This study demonstrated that cetuximab β plus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profile, offering a new treatment option for this patient population.

3579 Background: Panitumumab (Pmab) is a recombinant monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR) and it is indicated for the treatment of metastatic colorectal carcinoma (mCRC). However, the objective response rates (ORR) for the single agent are historically about 8-11%. EGFR inhibition induces synthetic lethality with poly ADP ribose polymerase inhibitors (PARPi) such as Niraparib, by attenuating DNA repair pathways. Combining PARP and EGFR inhibition has the potential to confer synergistic benefit, while also ameliorating resistance mechanism to EGFRi. We conducted this study to define the safety and efficacy of the combination of Niraparib and Pmab in RAS wildtype (WT) mCRC. Methods: Patients (pts) with RAS WT mCRC who have progressed on at least one line of systemic chemotherapy were eligible for the trial. Other selected inclusion criteria were ≥18 years of age, ECOG PS 0-1 and measurable disease per RECIST 1.1. Pmab was administered at 6 mg/kg IV on days 1 &amp; 15 of each 28-day cycle, while Niraparib was taken orally at 200mg or 300mg (based on body weight and platelet count) daily throughout the cycle. The primary endpoint was clinical benefit rate (CBR) defined as complete (CR) + partial (PR) response + stable disease (SD) per RECIST v1.1. Multiple secondary endpoints included safety/tolerability, ORR, progression-free survival (PFS), overall survival (OS), and duration of response (DoR). Results: A safety run-in cohort of 6 pts was initially enrolled. Following a preplanned safety analysis showing an acceptable toxicity profile, an additional 19 pts were enrolled. Of the total 25 enrolled pts, 24 were evaluable for response. Male - 50%; Whites/African Americans/Asians – 65.2%/21.7%/13%; median age – 58.5yrs. The majority had left sided tumor (92%) and the median line of prior therapy was 2 (range 1-4). CBR was 83.3% (0 CR, 6 PR, 14 SD) and ORR was 25%. mPFS – 5.6mos (95% CI: 3.7, 6.9); mOS – 20.9mos (95% CI: 9.2, NR). Six-month PFS and OS rates were 48.4% and 100% respectively. At a median follow up time of 7.5mos (95% CI: 4.2, 10.4), 3 patients remained on treatment and DoR was yet to be determined. Muco-cutaneous adverse events (AEs) of any grade included rash (58.4%), oral mucositis (20.8%), dry skin (16.7%) and paronychia (4.2%). Most common (grade &gt; 2) treatment related AEs (TRAEs) were anemia (G3; 12.5%), dermatitis, oral mucositis, hypertension and neutropenia (G3; 4.2% each). There were no grade 4-5 TRAEs. Conclusions: The combination of Pmab and Niraparib had an acceptable safety profile, and showed considerable antitumor activity in pts with advanced RAS WT mCRC compared to historical rates. Additional biomarker analyses such as survival correlation with immune cell infiltration in paired skin biopsies and HER2/BRAF mutational status are ongoing. Funding and product (Niraparib) for the study were provided by GSK (NCT03983993). Clinical trial information: NCT03983993 .

e15564 Background: Antiangiogenic therapy plus chemotherapy is one of the standard treatments in mCRC. Anlotinib, an oral small multi-targeted tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR α/β and c-kit, has demonstrated prolonged PFS in refractory mCRC. This trial was conducted to evaluate the efficacy and safety of anlotinib combined with CAPEOX as first-line treatment for unresectable RAS/BRAF wild-type mCRC. Methods: Patients aged 18-75, with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment and ECOG status ≤ 1were enrolled in 3 hospitals in Zhejiang, China. Enrolled patients received capecitabine (850 mg/m2 p.o., bid, on day 1-14 every 3 weeks), oxaliplatin (130 mg/m2 i.v., on day 1 every 3 weeks) and anlotinib (12 mg p.o. qd, on day1-14 every 3 weeks) as inducing therapy. After 6 cycles of combined therapy, patients who achieve complete response (CR)/ partial response (PR)/ stable disease (SD) would receive capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint is objective response rate (ORR); secondary endpoints included safety, disease control rate (DCR) and progression-free survival (PFS). Results: From November, 2019 to February, 2021, 31 patients had been enrolled. 1 patient was excluded for refused treatment. By now, 27 patients received at least 2 cycles of treatment and were available for efficacy evaluation: 22 patients had partial response (PR), 5 patients had stable disease (SD). The ORR was 81.5% (95% CI: 61.9–93.7%), and DCR was 100% (95% CI: 87.2–100%).1 patient received radical surgery after 6 cycles of treatment. The median PFS has not been reached yet. The most common grade≥3 AEs included hypertension (45.2%), neutropenia (25.8%) and diarrhea (12.9%). No treatment-related deaths occurred. Conclusions: The combination of anlotinib and CAPEOX showed promising antitumor activity and manageable toxicity in unresectable RAS/BRAF wild-type mCRC. Furthermore, we are launching a phase 3, multicenter, double-blind trial to further assess the efficacy of this regimen. Clinical trial information: NCT04080843. [Table: see text]

441TiP A multicenter, randomized, open-label, phase III study of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX as first-line therapy in patients with RAS/BRAF wild-type metastatic colorectal cancer

Background:Non-small-cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) mutations poses significant treatment challenges. While chemotherapy combined with immunotherapy or anti-angiogenic therapy has been explored, no standardized regimen exists for these patients. This study aims to evaluate the efficacy of different treatment regimens for HER2-mutated NSCLC.Objectives:Our study aimed to investigate the survival among NSCLC patients with HER2 mutation who received various treatment regimens in real-world settings, providing insights and guidance for clinical practice.Designs:Survival analyses were conducted on patients who underwent different treatment regimens, including chemotherapy, immunotherapy, tyrosine kinase inhibitors (TKIs), and combination therapies, to evaluate their effectiveness.Methods:This retrospective study included 118 patients diagnosed with HER2 mutations through next-generation sequencing at Zhejiang Cancer Hospital and Jinling Hospital affiliated with Nanjing University Medical School from September 2017 to December 2024. Data on treatment regimens and clinical outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), were collected. Kaplan–Meier analysis estimated PFS and OS, and Cox regression identified factors influencing PFS.Results:Among the 118 patients, ORR and DCR were 22.9% and 58.5%, respectively. Median PFS and OS were 7.3 and 44.9 months, respectively. Combination therapies significantly improved PFS compared to single chemotherapy or immunotherapy or TKIs group (7.8 vs 5.3 months, p = 0.001). Patients with brain metastases also showed better PFS with combination therapies (7.8 vs 2.8 months, p = 0.001). The chemotherapy, immunotherapy, and anti-angiogenic therapy combination (C + I + A) yielded the best outcomes, with a PFS of 16.3 months. Cox regression revealed treatment regimen as the only factor significantly influencing PFS.Conclusion:Combination regimens, especially C + I + A, significantly improve PFS and offer superior therapeutic benefits for patients with HER2-mutated NSCLC compared to single chemotherapy or immunotherapy or TKIs treatments.

Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.

e15064 Background: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and a key oncogene in solid tumors. Pyrotinib has been approved for the treatment of HER2-positive, recurrent or metastatic breast cancer. However, there are very few clinical studies on pyrotinib in other HER2-positive solid tumors. Therefore, more clinical evidence is urgently needed to guide pyrotinib-based therapy in HER2-positive non-breast advanced solid tumors. Methods: We retrospectively analyzed HER2-positive non-breast advanced solid tumors patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy in Henan Cancer Hospital between July 1, 2019 and December 2, 2021. In this study, 25 eligible patients were included with 16 patients with lung cancer, 6 with gastric cancer, 2 with colorectal cancer and 1 with cholangiocarcinoma. The primary end point was progression-free survival (PFS). Results: The median PFS and overall survival (OS) were 188 days (95% CI: 83–NA days) and 250 days (95% CI: 188–NA days), respectively. 16 patients with lung cancer and 6 patients with gastric cancer had a median PFS of 204 days (95% CI: 55–NA days) and 142 days (95% CI: 83–NA days), respectively. The median OS was 366 days (95% CI: 248–NA days) in patients with lung cancer and 179 days (95% CI: 90–NA days) in patients with gastric cancer. Patients receiving &gt; 3 lines of therapies had a numerically lower median PFS and OS than those receiving≤ 3 lines of treatments (PFS:188 vs 204 days, p=0.92; OS:188 vs 366 days, P = 0.43). All 25 patients were available for efficacy evaluation. The objective response rate (ORR) was 24% and disease control rate (DCR) was 68%. The ORR for lung cancer was 25% and for gastric cancer was 16.7%. In addition, the DCR for lung cancer was 62.5% and for gastric cancer was 66.7%. Moreover, patients receiving≤3 lines of treatments had a numerically higher ORR and DCR than those receiving &gt;3 lines of treatment (ORR:35.7% vs 9.1%,p=0.18; DCR:71.4% vs 63.6%, P＞0.99). The most common treatment-related adverse events (TRAEs) were diarrhea (84%), but only 3 (12%) patients reported grade 3 diarrhea which could be well controlled. Conclusions: These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-positive non-breast advanced solid tumors. This retrospective study is a pilot study aimed at promoting larger-scale studies to further clarify the safety and efficacy of pyrotinib in the treatment of non-breast solid tumors. Keywords: pyrotinib, HER2-positive, solid tumor, retrospective study, advanced solid tumors.

8096 Background: Epidermal growth factor receptor (EGFR) mutations, amplification, and K-ras mutations are known as predictive factor of the EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients (pts) with NSCLC. Prognostic influences of those biomarkers remain the matter to be discussed. Methods: Consecutive pts with advanced NSCLC who were examined EGFR genotype and received 1st line cytotoxic chemotherapy were enrolled. EGFR amplification and K-ras mutation were analyzed if sufficient tumor samples were available. Results: 87 pts were enrolled in this study. EGFR mutations or K-ras mutations were found in 26 of 87 (29.9%) or 2 of 65 (3.1%) pts, respectively. As to objective response rate (ORR), no significant differences were observed among pts with EGFR mutations, K-ras mutations, and pts without both mutations. Progression free survival (PFS) in 1st line cytotoxic chemotherapy was 8.4, 1.0, and 3.9 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. PFS was longer in pts with EGFR mutations compared with the pts without both mutations (p=0.0234). We also found the pts with K-ras mutations had shorter PFS compared with pts without both mutations (p=0.0203). Overall survival (OS) was 29.7, 2.3 and 13.4 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. Significant differences were found between pts with EGFR mutation and without both mutations (p=0.0001) and between pts without both mutations and with K-ras mutations (p=0.0001). Pts with EGFR amplification were found in 21 of 78 (26.9%). There were no differences between EGFR amplification positive and negative in terms of ORR, PFS and OS. 87 of 68 (78.2%) pts received EGFR-TKI therapy in the second line or later. As previously reported, both EGFR mutations and amplifications were good predictive marker of ORR, PFS and OS in pts treated with EGFR-TKI. Conclusions: EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker in first line cytotoxic chemotherapy. There is the possibility that EGFR and K-ras mutations have the prognostic impact in advanced NSCLC. [Table: see text]

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency &gt; 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.