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BackgroundCOM701, a novel first-in-class immune checkpoint inhibitor (ICI) binds to poliovirus receptor related immunoglobulin domain containing (PVRIG) leading to enhanced activation of T and NK-cells. COM701 in combination with nivolumab has a favorable safety profile, is well tolerated and demonstrates antitumor activity.1 We hypothesized that the addition of BMS-986207 as a triplet thereby inhibiting the DNAM axis will have an acceptable safety/tolerability profile. We present preliminary results on safety/tolerability and pharmacokinetics (PK) parameters.MethodsUsing an accelerated titration and 3+3 study design we enrolled 14 patients (pts) with advanced solid tumors. Doses of COM701 were 0.3, 1, 3, 10 or 20 [mg/kg IV Q4 wks]; in combination with nivolumab and BMS-986207 (both 480 mg IV Q4 wks). Key objectives were to evaluate the safety and tolerability, to determine the recommended dose for expansion (RDFE) and to characterize preliminary pharmacokinetic parameters. Key inclusion criteria: Age ≥ 18 yrs, histologically confirmed locally advanced or metastatic solid malignancy and has exhausted all available standard treatments. Key exclusion criteria: history of immune-related toxicities on prior immunotherapy treatment leading to discontinuation.ResultsIn the safety population [N=14], 12 pts reported treatment emergent adverse events (TEAEs). The most frequent TEAES [≥3 pts] were fatigue 5 pts (36%), pyrexia 3 pts (21%), vomiting 3 pts (21%). No DLTs were reported in any of the dose levels. The most frequent tumor types enrolled: CRC (n=3), and prostate, melanoma and OVCA/primary peritoneal cancer (n=2 each). Median number of prior therapies was 10 (range 1–19). Four pts had received prior immunotherapy. Serious adverse events [≥2 pts] were 2 pts (14%) with G3 abdominal pain, 2 pts (14%) with vomiting (1pt with G1/2 vomiting, 1 pt with G3 vomiting) all assessed by the investigator as unrelated to study drug. Preliminary PK profiles of COM701 were generally dose proportional.ConclusionsCOM701 in combination with BMS-986207 and nivolumab demonstrates a favorable safety, tolerability and PK profiles. COM701 20 mg/kg has been selected as the RDFE in combination with BMS-986207 and nivolumab (both 480 mg) all administered IV Q4 wks. The expansion cohorts are enrolling pts with platinum resistant ovarian cancer and endometrial cancer. Data cutoff 28 Jun 2021.AcknowledgementsThis study is in collaboration with Bristol Myers Squibb.Trial RegistrationNCT04570839ReferencesVaena, DA, Fleming GF et al. COM701 with or without nivolumab: Results of an ongoing phase 1 study of safety, tolerability and preliminary antitumor activity in patients with advanced solid malignancies (NCT03667716). J Clin Oncol 2021;39: (suppl 15; abstr 2504).Ethics ApprovalThe study obtained ethics approval form all the participating sites. All study participants gave informed consent before taking part.- 0002: START2020.15- 0003: 20210109- 0005: IRB20-1549- 0006: 21-060- 0007: IRB-AAAT4904- 0012: 2020-0755- 0013: STMW2020.16- 0015: 20210109

BackgroundCOM902 is an IgG4 fully human high-affinity monoclonal antibody, inhibitor of TIGIT (T cell Ig and immunoreceptor tyrosine-based inhibitory motif [ITIM] domain) binding to poliovirus receptor (PVR). TIGIT blockade by COM902 was shown to enhance anti-tumor immunity in pre-clinical models. We hypothesized that COM902 as monotherapy will have an acceptable safety and tolerability profile in subjects with advanced solid tumors.MethodsUtilizing an accelerated titration and 3+3 study design we enrolled 18 patients (pts) at the following COM902 doses 0.01, 0.03, 0.1, 0.3, 1, 3 and 10 mg/kg IV Q3 wks. Key primary objectives were to evaluate the safety, tolerability (CTCAE v5.0), to characterize the pharmacokinetics (PK) and to select a recommended dose for expansion (RDFE). An exploratory objective was evaluation of peripheral receptor occupancy (RO). Key inclusion criteria: Age ≥18 yrs, histologically/cytologically confirmed advanced malignancy who have exhausted all available standard therapy or not a candidate for standard therapy. Patients with performance status ECOG 0-1, prior ICI permissible. Dose-limiting toxicities (DLTs) were evaluated within a 21-day window in the 1st cycle of dose escalation.ResultsIn the safety population [N=18], 12 pts reported treatment emergent adverse events (TEAEs). The most frequent TEAES [≥2pts] were fatigue 7 pts (39%) all G1/2, diarrhea 3 pts (17%) all G1/2. Two pts reported DLTs deemed related to study drug, a pt with G2 nausea (single pt cohort, 0.01 mg/kg) and a pt with G3 atrial fibrillation (1 mg/kg). Serious adverse events were reported in 2 pts, 1 pt with atrial fibrillation (deemed by the investigator as possibly related to COM902) and 1 pt with spinal cord compression (deemed by the investigator as unrelated to COM902, related to disease). Preliminary PK profiles were generally dose proportional and peripheral RO above 90% was reported from 0.1 mg/kg dose.ConclusionsCOM902 has an acceptable safety, tolerability and PK profiles. A COM902 3 mg/kg IV Q3 wks is the RDFE. Enrollment into combination cohort (COM902 + COM701), for evaluation of safety/tolerability at the RDFE of both study drugs, combination dose expansion (COM902 + COM701) in pts with HNSCC, NSCLC and CRC-MSS and COM902 monotherapy dose expansion (pts with multiple myeloma) all at the RDFE of study drug(s) are planned. Data cut June 28, 2021.Trial RegistrationNCT04354246Ethics ApprovalThe study obtained approval from IRBs of the participating clinical trial sites. The study participants gave informed consent before taking part.o 0002: MOD01006350 (START)o 0003: 20202320 (West Cancer Center)o 0012: 2020–0195 (MDACC)o 0013: MOD01006350 (START midwest)o 0014: 20202320 (OSU)

2504 Background: COM701 is a novel first in class humanized IgG4 monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG), blocking its interaction with its ligand, PVRL2. Blocking of PVRIG leads to enhanced activation of T/NK cells and in mouse models inhibits tumor growth. We report new and updated results on safety/tolerability/pharmacokinetics and antitumor activity from this ongoing study including final results in dose escalation combination cohort, monotherapy expansion cohort (MEC). Methods: We enrolled a total of 51 DLT-evaluable pts: Arm A (COM701 mono dose escalation), 16 pts in 8 cohorts (0.01 – 20 mg/kg IV Q3/4 wks); Arm B (COM701 0.3 – 20 mg/kg + nivolumab (NIVO) 360 mg/480 mg IV Q3/Q4 wks), 15 pts in 5 cohorts; 20 pts in MEC (NSCLC, OVCA, breast, endometrial and CRC) at the recommended dose for expansion(RDFE), 20 mg/kg IV Q4 wks. Key inclusion criteria: Age ≥18 yrs, histologically confirmed metastatic solid malignancy, has exhausted available standard tx, ECOG 0-1, prior ICI permissible (except prior tx with a PVRIG inhibitor). Key exclusion criteria: active autoimmune disease requiring systemic tx, hx inflammatory lung disease. Primary objectives – safety/tolerability of COM701 ± NIVO (AEs, CTCAE v4.03), PK, RDFE. Key secondary/exploratory objectives - antitumor activity of COM701 ± NIVO (RECIST v1.1), evaluation of PVRL2 expression in tumor biopsy, blood cytokines and immunophenotyping. Results: No DLTs were reported in Arms A or B. COM701 PK profile similar in Arm A, 20 mg/kg IV Q4 wks (cohort 8) and Arm B cohort 5 (COM701 20 mg/kg + NIVO 480 mg; all IV Q4 wks). Frequency of TEAEs in safety population (N=54 pts): pts on COM701 mono (N=38)- No AE (4), Grade≤2 (21), G3 (11), G4 (1), G5 (1, PD), pts on combo (N=16) - Grade≤2 (8), G3 (7), G5 (1, PD). Serious TEAE: pts on COM701 mono 11/38, pts on combo 6/16. Most frequent AEs in Arm A: Grade ≤2 fatigue 12/38 pts (31%), nausea 9/38 (23%); Arm B: fatigue 7/16 pts (44%) and AST increased 4/16 pts (25%). Antitumor activity - in Arm A (cohort 8), a pt with platinum resistant primary peritoneal cancer had confirmed PR ongoing 14 months. In Arm B (COM701 10 mg/kg + NIVO 480 mg, all IV Q4 wks), a pt with anal SCCA; confirmed CR, ongoing 18 months, last tx with prior PD on NIVO. In addition, a pt with renal cell CA had confirmed SD [ongoing 13 months, COM701 0.3 mg/kg + NIVO 360mg; IV Q3 wks],] In MEC, 30% (6/20 pts) had best response of SD [1-endometrial, 3 NSCLC, 2 OVCA], 2 pts [NSCLC, OVCA] ongoing at 6/4 months. Overall 16pts had prior tx-refractory disease, 9(56%) had best response of ≥SD. Of 18 pts with prior tx with ICI, 13 (72%) had best response of ≥SD. Datacut 14Dec2020. Conclusions: COM701 ± NIVO well tolerated with no new safety signals. Encouraging signal of antitumor activity including in pts with prior tx with ICI or prior tx-refractory disease. Clinical trial information: NCT03667716..

This short-term longitudinal study sought to identify the issues faced by a group of international Chinese students undertaking study in an Australian university. While the focus was on educational issues, socio-cultural and personal factors were also examined in an attempt to identify the sorts of strategies students used in settling into a new socio-cultural and educational context. Interviews conducted at the beginning and end of the first semester of study indicate a range of issues that are supported by previous studies. What has not previously been highlighted, however, is the emphasis on speaking and listening skills which students reported they needed to improve. Lack of proficiency in these areas was seen by students as hampering their active participation in class, leading to lack of confidence in approaching Australian students, and resulting in their inability to benefit from the “Australian experience”. Many existing academic support structures in Australian universities tend to emphasize sup...

e13109 Background: Many multigene panel (MGP) options are available for hereditary cancer testing. Previously, management guidelines were only published for a few high-risk genes, but now such guidelines exist for most genes on MGPs. Many clinicians question which MGP(s) may be most appropriate for their patients. We examined the likelihood of a positive result for patients diagnosed with breast cancer (BC) or colorectal cancer (CRC) across several MGPs and assessed the potential impact of these results on patient care. Methods: Positive results, defined by the presence of at least one pathogenic or likely pathogenic variant, were assessed for patients with BC or CRC across various MGPs ordered 6/2012-6/2016 at one commercial laboratory. For BC, the MGPs used for comparison were a high-risk BC panel (up to 6 genes), a comprehensive BC panel (up to 17 genes), and a multi-cancer panel (up to 32 genes). For CRC, a comprehensive CRC panel (up to 17 genes) was compared to the 32 gene multi-cancer panel. Results: For both BC and CRC patients, the utilization of a MGP with more genes led to more positive results than a MGP with fewer genes, with the vast majority of additional findings occurring in genes with published management guidelines (Table). Conclusions: The majority of positive results occurring in genes on larger MGPs, but not smaller MGPs, are in genes with published management guidelines.These results can impact treatment decisions and cancer risk management, including earlier and/or more frequent screening, chemoprevention, and/or other measures. In some cases, positive results occurred in genes not associated with the patient’s cancer diagnosis, but may still impact risk management for other cancer(s). Further studies are needed to determine the impact of larger MGPs on clinical outcomes for patients and their families. [Table: see text]

Gastric volvulus is characterized by abnormal rotation of the stomach around an axis made by two fixed portions. Symptoms of gastric volvulus range from anemia and weight loss to severe epigastric or chest pain associated with nonproductive vomiting or upper gastrointestinal bleeding. Ischemia, necrosis, and perforation will occur if this condition remains untreated. We report a case of a 92-year-old patient with acute gastric volvulus treated with laparoscopic reduction and anterior gastropexy. We suggest that the laparoscopic approach to gastric volvulus is safe and feasible and should be considered. High-risk and elderly patients can particularly benefit from minimally invasive access. Anterior gastropexy palliates the symptoms and can be considered a definitive treatment in this patient population.