2064 Background: Recurrent glioblastoma (rGBM) following chemoradiation is associated with a poor prognosis. While bevacizumab is the most common salvage therapy, responses remain brief and without an associated survival benefit. Resistance may involve overexpression of Fatty Acid Synthase (FASN). Our institution is conducting a phase 2 study of bevacizumab with FASN inhibitor TVB-2640 in patients with GBM in first relapse. Methods: This is a prospective, phase 2 study of bevacizumab with TVB-2640 in patients with GBM in first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age ≥ 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. Randomization into two arms for the first 28 days is included for exploratory biochemical analysis: patients in arm 1 receive bevacizumab every 2 weeks in combination with TVB-2640; those in arm 2 receive bevacizumab alone every 2 weeks. MR-Spectroscopy (MRS) and serum sampling for exosome analysis are obtained on patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converge to a single arm and continue to receive bevacizumab in combination with TVB-2640. Results: We have enrolled 24 patients to date; 23 have started treatment. Of those 23 patients, 10 have died, 4 have progressed but are still alive, 2 withdrew, and 7 are still active on trial. The PFS6 is and OS9 are both currently 50%, which compares favorably with historical controls. There have been no reports of grade 4 or 5 treatment-related AEs (of note, 2 deaths were thought definitely unrelated to treatment, including 1 case of intracerebral hemorrhage, and 1 case of sepsis). There have been two cases of grade 3 hand-foot syndrome thought definitely related to treatment. Updated results will include PFS, response, and biomarker analysis (exosome, MRS). Conclusions: The combination of TVB2640 with bevacizumab appears be well tolerated. PFS6 and OS9 are both currently 50%. The study has completed accrual with final data expected later in 2019. Clinical trial information: NCT03032484.

Background: Central nervous system (CNS) neoplasms are relatively uncommon and potentially debilitating. From 1984-2012, there were around 200 new cases of malignant primary brain tumours each year in Hong Kong, and the trend has been static. To improve epidemiological reporting of CNS tumours in Hong Kong, the Hong Kong Cancer Registry (HKCaR) has established the brain and CNS tumour registry (BCTR) to collect all incident cases of primary malignant and non-malignant CNS tumours since 2013.Methods: The HKCaR is a population-based cancer registry in Hong Kong. Clinical records and pathology reports were obtained from public and private care providers with high coverage of 95%. These records were entered, cleansed and validated. Incidence of pathologically or clinically diagnosed CNS tumours with malignant, benign or uncertain behaviours were reported over the period of 2013-2017. The incidence were age-standardized with the 2000 US standard population and compared with US data from CBTRUS.Results: The age-standardised incidence of malignant and non-malignant brain tumours pooled over the period of 2013 to 2017 were 3/100,000 population and 8.6/ 100,000 population respectively. The top three most common types of malignant neoplasms were glioblastoma, other glial tumours and embryonal tumours; and in non-malignant neoplasms being meningioma, pituitary tumours and nerve sheath tumours. The incidence of both malignant and non-malignant tumours were around half of that in the US (7.08 and 16.33 per 100,000 population in the period of [2012][2013][2014][2015][2016]. The incidence of non-malignant and malignant brain tumours both increases significantly with age, with steep increment for non-malignant tumours starting from age of 45-64 and for malignant after the year of 65. The incidence rate in the whole population and in each age group has remained static over the reported years.Conclusions: Significant geographical differences in incidence of CNS tumours was observed between Hong Kong and the US. Under-diagnosis of brain tumour is unlikely due to easy access to public healthcare service and cross sectional imaging. The difference may be due to ethnic and environmental factors, which include higher rate of allergic conditions in Hong Kong which may confer protection. Further investigations are warranted.Legal entity responsible for the study: The authors.

Purpose: Glioblastoma (GBM) represents the most common primary brain tumor. Although anti-angiogenics are employed in the recurrent setting, they do not prolong survival. GBM is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity. Patients and Methods: We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomized to TVB-2640 (100mg/m2 oral daily) plus bevacizumab (10mg/kg IV, D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease. The primary endpoint was progression-free survival. Results: A total of 25 patients were enrolled. The most frequently reported AEs were palmar-plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue and skin infection. Most were Grade 1 or 2 in intensity. The ORR for TVB-2640 plus bevacizumab was 56% (CR 17%, PR 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%, p=0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log rank test (p=0.56). Conclusions: In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.

TPS8074 Background: Engineered toxin bodies (ETBs) are comprised of a proprietarily engineered form of Shiga-like Toxin A subunit (SLT-A) genetically fused to antibody-like binding domains. ETBs work through novel mechanisms of action and are capable of forcing internalization, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation of ribosomes. MT-3724 represents a novel ETB modality comprised of an anti-CD20 single-chain variable fragment genetically fused to SLT-A. It is capable of efficient internalization once bound to CD20 and can induce potent direct cell-kill via enzymatic ribosome inactivation. MT-3724 is currently being studied in three ongoing Phase 2 studies for relapsed or refractory diffuse large B-cell lymphoma (r/rDLBCL). Methods: The primary objective of this single-arm, Phase 2 study (NCT02361346) is to determine the efficacy of MT-3724 monotherapy in r/rDLBCL based on overall response rate (ORR), defined as the proportion of subjects with a complete/partial response according to the Lugano criteria, as assessed by independent, central review. Key secondary objectives include safety, progression-free survival, investigator‐assessed ORR, duration of response, overall survival, and pharmacodynamics. Adverse events will be assessed and documented according to Common Terminology Criteria for Adverse Events version 5.0. Key eligibility criteria include adult subjects with histologically confirmed, r/rDLBCL, with ≥2 prior standard of care systemic NHL treatment regimens, and ≥1 measurable lesion. As rituximab and other CD20-targeting antibodies compete with MT-3724 for the same CD20 domain, minimum washout periods from these agents must be observed. Subjects remain eligible post stem cell transplant or chimeric antigen receptor T-cell therapy. Subjects will receive 50 µg/kg MT-3724 IV over 1 hour on Days 1, 3, 5, 8, 10 and 12 of a 21-day treatment cycle. The anticipated sample size is N = 100. Interim analyses will be performed to confirm minimum efficacy thresholds based on the encouraging data observed in the completed phase 1 portion of the study [Hamlin et al. Blood 2019;134(Suppl 1):4098]. Multiple global sites are enrolling subjects. Clinical trial information: NCT02361346 .