All times are listed in CEST (Central European Summer Time)

Displaying One Session

Mini Oral session
Date
18.09.2020
Chairs
  • Matthias Preusser (Vienna, Austria)
  • Hanna Maenpaa (Helsinki, Finland)
  • Nicolaus Andratschke (Zurich, Switzerland)
Mini Oral - CNS Mini Oral session

Open & welcome

Speakers
  • Matthias Preusser (Vienna, Austria)
Session Name
Mini Oral - CNS Mini Oral session

365MO - Exploring changes in glioblastoma treatment patterns in Europe and the USA with population-based cancer registry data

Presentation Number
365MO
Speakers
  • Francesco Giusti (Ispra, Italy)
Session Name

Abstract

Background

Glioblastoma (GBM) is the most common and aggressive primary brain tumour. Since the EORTC 2005 trial (Stupp et al.) standard treatment has been temozolomide in combination with radiotherapy. In Europe and the US many population-based cancer registries (CRs) gather data on treatment, which can be used to assess care patterns at population level. This analysis reports on GBM treatment in Europe and US in the period before and after the change in clinical practice.

Methods

Data from CRs contributing to the European Cancer Information System having submitted treatment information and data from the US National Cancer Institute Surveillance (NCI), Epidemiology and End Results (SEER) were analysed, selecting patients diagnosed in 1999-2013 with GBM as first tumour. The proportion of cases by treatment type was calculated for radiotherapy (RT) and RT plus systemic therapy (RT+ST) and overall survival was compared by period (1999-2003 vs 2009-2013) and area.

Results

34,229 cases from 17 CRs in 11 European Countries – 3 each in Eastern, Northern and Western Europe, 2 in Southern Europe – and 36,925 cases from 18 US CRs were analysed. In Europe 45% of cases received RT and 14% RT+ST in 1999-2003. The percentages were 28% RT, 32% RT+ST in 2004-2008 and 21% RT, 44% RT+ST in 2009-2013. Treatment modality distribution was similar in the four European areas. In the US therapy was RT for 38% and RT+ST for 27% of patients in 1999-2003. The percentages were 13% RT, 55% RT+ST in 2004-2008 and 9% RT, 62% RT+ST in 2009-2013. In Europe two-year overall survival was 10% for RT and 20% for cases with RT+ST in 1999-2003, rising to 25% for RT+ST in 2009-13. In the US it was 7% for RT cases and 13% for those with RT+ST in 1999-2003, rising to 9% for RT and 26% for RT+ST in 2009-2013.

Conclusions

A change in treatment modality for GBM was observed between the considered periods, showing that the switch to RT+ST modality has been more marked in the US. Two-year survival differences between patients treated with RT and those with RT+ST are similar in Europe and the US, showing that likely more European patients would benefit if the RT+ST percentage could rise to the US level. CRs could be a powerful tool to assist clinical research and monitor treatment patterns and effects in the population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

366MO - Incidence of malignant and non-malignant CNS tumours in Hong Kong

Presentation Number
366MO
Speakers
  • Ka Man Cheung (Kowloon, Hong Kong PRC)
Session Name

Abstract

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 2012-2016). 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.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

367MO - Association between socioeconomic status and survival in glioblastoma: An Italian single-centre prospective, observational study

Presentation Number
367MO
Speakers
  • Lidia Gatto (Bologna, Italy)
Session Name

Abstract

Background

There is some evidence that the socioeconomic status (SES) is associated with survival in glioblastoma (GBM), but the findings are limited. We conducted a single centre prospective observational study investigating the association between SES and GBM survival in Italy, where exists a national health service that provides universal coverage.

Methods

This study was a prospective analysis of newly diagnosed GBM patients who underwent chemoradiation between 2018 and 2020 in a hub center for brain cancer research. The SES was measured using the income-brackets, extracted from regional health administrative system. The income-brackets refer to annual gross family income: up to 36,152 euros in income is classified as R1 bracket; between 36,153 and 70,000 euros as R2; between 70,0001 and 100,000 euros as R3; over 100,000 euros as R4.

Results

One hundred six patients were included in the study. In multivariable cox proportional hazard model of survival, a high available income was associated with improved survival HR= 0.623 (95% CI 0.467-0.832; p = 0.001). When adjusted for age, survival remained improved for high-income patients.

Conclusions

We confirm that SES is an important determinant of prognosis in GBM even in the Italian National Health Service which provide universal, largely free and relatively comprehensive healthcare. Despite aspirations to achieve equality in healthcare, socioeconomic differences exist and may impact on clinical outcome.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

Invited Discussant 365MO, 366MO and 367MO

Speakers
  • Matthias Preusser (Vienna, Austria)
Session Name
Mini Oral - CNS Mini Oral session

368MO - Fatty acid synthase inhibitor TVB-2640 with bevacizumab in recurrent glioblastoma

Presentation Number
368MO
Speakers
  • William Kelly (San Antonio, TX, United States of America)
Session Name

Abstract

Background

Standard of care for glioblastoma (GBM) is surgical resection followed by chemoradiation and tumor treatment fields, with bevacizumab (bev) given at relapse. Responses to bev remain brief; and resistance may involve overexpression of Fatty Acid Synthase (FASN).

Methods

We performed prospective phase 2 study of bev with oral FASN inhibitor TVB-2640 in patients with rGBM at first relapse. Primary end point was progression free survival (PFS) with comparison to bev single agent outcomes from BELOB. Inclusion criteria included adults with GBM progression following standard combined modality treatment. An exploratory phase randomization into 2 separate arms of single agent bev or in combination with TVB-2640 with MR-Spectroscopy (MRS) and serum sampling for exosome analysis was obtained on all patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converged to a single arm and continued to receive bev in combination with TVB-2640.

Results

A total of 28 patients were enrolled, 3 failed screening. 23 came off study and 2 are active. No grade 4 or higher treatment-related AEs have occurred, with Grade 3 events included 3 cases of palmar-plantar erythrodysesthesia; 1 each of hypertension, stomatitis, optic neuritis, DVT, and wound infection. A 66.7% overall response rate (ORR) was observed and 95% of patients have achieved at least stable disease by RANO Criteria. Median time to progression was 5.9m, which was statistically superior to historical controls. Median overall survival (OS) was 10.1m with an OS12 of 40%. Biomarker analysis (exosome, MRS) is pending.

Conclusions

The combination of TVB-2640 with bev appears well tolerated with improved progression free and overall survival compared to historical controls. Additional studies are warranted. Final data analysis as well as exploratory biomarker analysis will be presented.

Clinical trial identification

NCT03032484.

Legal entity responsible for the study

Mays Cancer Center at UTHSA.

Funding

Kolitz and Johnson Endowments for Neuro-Oncology Research.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

369MO - Final results of depatuxizumab mafodotin plus temozolomide in recurrent glioblastoma patients: Real-world experience from a multicenter study of Italian Association of Neuro-Oncology (AINO)

Presentation Number
369MO
Speakers
  • Marta Padovan (Padova, Italy)
Session Name

Abstract

Background

Precision medicine is a promising tool in oncology. DepatuxM is a new antibody-drug conjugate, consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The Intellance2/EORTC 1410 phase-II trial, showed interesting results for DepatuxM + TMZ combination in EGFRamplified glioblastoma patients at first recurrence after RT and TMZ. In our study, we investigated clinical outcome and safety of this combination used in recurrent GBM PTS as “compassionate use”.

Methods

PTS were enrolled from 7 centres of AINO and followed prospectively. Major inclusion criteria were: histologically confirmed diagnosis of GBM, 1 or more prior systemic therapies, ECOG PS ≤ 2 and EGFRamplified (FISH). Patients received DepatuxM 1.25 mg/kg every two weeks + TMZ until disease progression or unacceptable toxicity. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events.

Results

From October 2018 to June 2019, we enrolled 36 PTS: median age was 57, ECOG PS 0-1 in 88% of PTS, MGMTmet in 64%, 42% received the treatment as second line therapy. At the time of analysis, 24 PTS (67%) had died and 31 PTS (86%) had progressed. Median OS was 8.04ms (95%CI 5.3-10.7), 12m OS was 37%; medianPFS was 2.1ms (95% CI 1.7-2.4), 6ms PFS was 38%. All PTS were evaluable for response: disease control rate was 47%: stable disease was reported in 36%, partial response in 11% and complete response in 3% of PTS. Drug-related adverse events led to dose reductions of DepatuxM in 17% of PTS, in 28% was delayed and in 5% was permanently discontinued. Grade 3 ocular toxicity occurred in 11% of patients, no grade 4 ocular toxicity was reported; no death was considered drug-related.

Conclusions

We report the first “real world” experience of DepatuxM + TMZ in recurrent GBM. We showed encouraging clinical benefit, despite most patients were treated beyond the second-line of therapy. Overall, the results are closed to those reported in previous phase II trial. Toxicity was moderate and manageable. This combination would be re-considered as a potential treatment for this setting of patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

370MO - FOLAGLI: A phase I study of folinic acid combined with temozolomide and radiotherapy to modulate MGMT gene promoter methylation in newly diagnosed MGMT non-methytated glioblastoma

Presentation Number
370MO
Speakers
  • Jean-Sebastien Frenel (Saint-Herblain, CEDEX, France)
Session Name

Abstract

Background

Glioblastoma is a very aggressive disease with a poor prognosis. The MGMT gene encodes an enzyme involved in DNA repair, the epigenetic silencing (by methylation) of which confers a better prognostic for GBM patients. We hypothesized that administration of folic acid could restore a methylation of MGMT promoter gene in non-methylated GBM and thus increase sensitivity to temozolomide combined with radiotherapy.

Methods

FOLAGLI is a non-randomized, phase 1 open study, with dose escalation (3+3 design) and expansion cohort of folic acid in combination with temozolomide and radiotherapy for newly diagnosed glioblastoma harboring non-methylated MGMT gene promoter detected by semi quantitative methyl-specific PCR. The study assessed the tolerability, pharmacodynamics and efficacy of folic acid dose escalation from 5 to 60 mg daily, given 30 minutes before temozolomide.

Results

Between March 2013 and March 2019, 90 patients were screened of whom 66 had a MGMT promoter methylated tumor. Finally, 24 patients were enrolled and one patient withdrew his consent. Median age was 56 years old [range 42-73]. No dose limiting toxicity was reported in the phase I part. The recommended dose for the expansion phase was 60 mg. Grade 1-2 treatment-related adverse events (AEs) occurring in ≥2 patients included asthenia (n=6), lymphopenia (n=2), nausea (n=3) and vomiting (n=3), alopecia (n=2) and anemia (n=2). Grade III AEs related to treatment occurring in ≥1 patients included lymphopenia (n=2), thrombocytopenia (n=1), neutropenia (n=1), dehydration (n=1) and hypoacousia (n=1). No grade IV AES occurred. With a median follow-up of 18.3 [8.5-65.5] months, median progression free survival (PFS) was 7.9m [7.1-8.3]. The median overall survival (OS) was 17.1m [12.6-24.5] and 6, 12 and 24 months OS rate were 100%, 79.8% [54.6-91.9] and 28.2 [9.2-51.2] respectively. For the eight patients with ctDNA monitoring, the combination of folic acid with temozolomide showed restoration of methylation on of the promoter of MGMT detected in ctDNA.

Conclusions

Preliminary safety and efficacy results suggest that folic acid combined with temozolomide and radiotherapy is well tolerated and feasible.

Clinical trial identification

NCT01700569.

Legal entity responsible for the study

Institut de Cancerologie de L'Ouest.

Funding

Institut National du Cancer.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

Invited Discussant 368MO, 369MO and 370MO

Speakers
  • Hanna Maenpaa (Helsinki, Finland)
Session Name
Mini Oral - CNS Mini Oral session

371MO - Usefulness of circulating tumour DNA detection from cerebrospinal fluid in recurrent high-grade glioma

Presentation Number
371MO
Speakers
  • Maxime Fontanilles (Rouen, France)
Session Name

Abstract

Background

Molecular characterization of high-grade glioma (HGG) at recurrence is promising for disease monitoring and therapeutic decision. We aimed to analyze the mutational profile between primary tumor and circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) obtained at recurrence in patients treated for a HGG.

Methods

This prospective pilot trial included patients suffering from HGG at the time of recurrence, defined by RANO criteria, after standard radiotherapy and temozolomide treatment. CSF (2mL) was collected by lumbar puncture within 3 weeks after recurrence MRI. ctDNA from CSF and DNA from primary tumor (tDNA) were both sequenced using next-generation sequencing (NGS) Illumina Miseq® with custom targeted panel dedicated to HGG hotspot mutations.

Results

Eighteen patients were included (16 IDH-wild type glioblastoma, 1 gliosarcoma and 1 anaplastic astrocytoma). Two-thirds (10/15) of patients had somatic mutations in CSF (ctDNA+) at recurrence (3 pts had insufficient ctDNA amount). Mutational profile differed between tDNA at baseline versus ctDNA at recurrence, especially regarding altered genes frequencies: PTEN 37.5% vs 26.7%, TERT 43.8% vs 20%, TP53 13.3% vs 20% and ATRX 31.3% vs 13.3%. Interestingly, two patients harbored de novo driver mutations (IDH2 and MSH6) in ctDNA at recurrence. Regarding factors associated with ctDNA+: 7/10 had CSF protein level >.55g/L with a mean of 1.17 g/L for ctDNA+ vs .65 g/L for ctDNA-, p=.06. Whole circulating cell-free DNA concentration also correlated to CSF protein content (Rsquared 0.4, p=.003). The 1-year overall survival was 90% in ctDNA+ group and 40% in ctDNA- group.

Conclusions

ctDNA from CSF is a promising and minimally-invasive tool to characterize molecular evolution of HGG after RT-TMZ treatment in a subset of patients. Meningeal inflammation likely influences ctDNA detection in CSF.

Legal entity responsible for the study

The authors.

Funding

GIRCI Nord-Ouest.

Disclosure

M. Fontanilles: Travel/Accommodation/Expenses: La Roche-Hoffman; Travel/Accommodation/Expenses: GSK. All other authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

372MO - Melanoma leptomeningeal metastases: A European multicenter cohort

Presentation Number
372MO
Speakers
  • Emilie Le Rhun (Zurich, CEDEX, Switzerland)
Session Name

Abstract

Background

Among solid cancers, melanoma may have the greatest affinity for the central nervous system. The development of systemic treatment approaches and their combination with local therapy have improved the prognosis of melanoma patients with brain metastases. However, only few contemporary cohorts of melanoma patients with leptomeningeal metastases (LM) have been reported.

Methods

We retrospectively reviewed files of 51 melanoma patients with newly diagnosed LM from 7 European centers. The clinical description, brain or cerebrospinal MRI, and CSF data at diagnosis had to be available. EANO ESMO criteria for LM were retrospectively applied.

Results

At LM diagnosis, median age was 60 years (interquartile range - IQR: 44-66), median Karnofsky performance score (KPS) was 70 (IQR: 60-90%). Clinical signs were noted in 44 patients (86%). CSF tumor cells were noted in 38 patiens (74%). The most frequent MRI presentation was linear disease (EANO ESMO type A) (n=21, 41%), then combined linear and nodular disease (EANO ESMO type C) (n=16, 31%). The diagnosis was confirmed for 39 patients (76%), probable for 10 (20%), possible in 2 (4%). A BRAF mutation was noted in 38 tumors (76%). Systemic treatment was administered in 23 patients (51%), including targeted therapy in 13 (56%) and immunotherapy in 3 (13%). Patients with BRAF-mutated tumors received systemic treatment in 22 cases (58%), including targeted therapy in 13 patients (59%). Intrathecal treatment was given in 23 patients (45%). Whole brain radiotherapy was used in 16 patients (31%), 33 patients (65%) had no brain radiotherapy. The combination of systemic and intrathecal treatment (n=13, 25%) was the most commonly used combination. No specific treatment was given to 11 patients (22%). Median OS for the whole cohort was 1.7 months (IQR: 0.9-5.2). Median OS was 1.5 months (0.8-4.3) in type I LM versus 2.2 months (1.5-8.1) in type II LM; 1.9 months (IQR: 0.9-4.5 months) in BRAF mutated tumors versus 4.6 (IQR:1.4-8.6) in the BRAF non-mutated tumors; and 1.4 (IQR: 0.5-1.6) without versus 2.9 months (IQR: 1-6) with treatment.

Conclusions

The prognosis of LM in melanoma patients remains poor despite novel systemic treatment options. New therapeutic approaches are urgently needed in this population.

Legal entity responsible for the study

University Hospital Zurich (2017-02098).

Funding

Has not received any funding.

Disclosure

E. Le Rhun: Advisory/Consultancy: Tocagen; Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy: Daiichi Sankyo. K. Seystahl: Advisory/Consultancy: Roche. M.J. van den Bent: Advisory/Consultancy: Bayer; Advisory/Consultancy: Carthera; Advisory/Consultancy: Nerviano; Advisory/Consultancy: Agios; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy: Karyopharm; Advisory/Consultancy: Genenta. M. Preusser: Advisory/Consultancy: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche; Advisory/Consultancy: BMJ Journals; Advisory/Consultancy: MedMedia; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Lilly; Advisory/Consultancy: Medahead; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Merck, Sharp & Dohme; Advisory/Consultancy: Tocagen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Germon Lehrman Group; Advisory/Consultancy: GMC Contrast; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Mundipharma. F. Wolpert: Travel/Accommodation/Expenses: Roche. U. Herrlinger: Advisory/Consultancy: Medac; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novocure; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Noxxon; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bayer; Advisory/Consultancy: Janssen; Advisory/Consultancy: Karyopharm. L. Mortier: Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Research grant/Funding (institution): Pierre Fabre. R. Dummer: Advisory/Consultancy: Novartis; Advisory/Consultancy: Merck Sharp & Dhome (MSD); Advisory/Consultancy: Bristol-Myers Squibb (BMS); Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Catalym; Advisory/Consultancy: Second Genome; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Alligator. M. Weller: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Adastra; Research grant/Funding (institution): Dracen; Advisory/Consultancy, Research grant/Funding (institution): Merck, Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Merck (EMD); Advisory/Consultancy, Research grant/Funding (institution): Novocure; Advisory/Consultancy: Orbus; Advisory/Consultancy: Basilea; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Medac; Advisory/Consultancy: Roche; Advisory/Consultancy: Tocagen. All other authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

373MO - Delivery and activity of SN-38 by sacituzumab govitecan in CNS tumours

Presentation Number
373MO
Speakers
  • Andrew J. Brenner (San Antonio, United States of America)
Session Name

Abstract

Background

Sacituzumab Govitecan (SG, TRODELVY™) is unique as an antibody drug conjugate, with payload and linker characteristics preferable for CNS delivery. SG utilizes a pH hydrolysable linker, allowing SN-38 to be released at the tumor site, making the drug accessible to surrounding tumor cells. The payload, SN-38, is a topoisomerase inhibitor which crosses the blood-brain barrier and is a drug partner in CNS regimens. We have observed SG activity in intracranial xenograft models. We therefore hypothesized that SG would achieve therapeutically relevant concentration of SN-38 within the CNS.

Methods

We initiated a prospective, single center, window of opportunity trial (NCT03995706) to examine the intra-tumoral concentrations of SG, SN-38, and SN-38G in patients undergoing craniotomy for breast cancer brain metastases (BCBM, n=10) or recurrent glioblastoma (rGBM, n=10). Patients received a single dose of SG at 10mg/kg IV the day prior to craniotomy. Tumor and corresponding serum were collected intra-operatively. Total SN-38 concentrations were analyzed via ultrahigh-performance liquid chromatography−high resolution mass spectrometry (UHPLC-HRMS). Patients resumed SG 10mg/kg IV days 1 and 8 of 21 day cycle following recovery and were assessed every third cycle by MRI using RANO criteria.

Results

To date 14 patients have been treated, including 7 BCBM and 7 rGBM. No new safety signals have been observed. UHPLC-HRMS analysis was performed in the first 10 tumors (n=4 and 6 respectively). For the rGBM patients, total concentration of SN-38 varied from 93nM to 680nM, with a mean concentration of 420nM. For BCBM, total concentration of SN-38 varied from 173nM to 1160nM, with a mean concentration of 626nM. All GBM patients had residual measurable disease and 4 breast patients had measurable disease. With a median follow up of 12 weeks from the first postoperative cycle, we have observed 2 partial responses by RANO criteria within the brain from each group (ORR of 28% and 50% at 12 weeks respectively).

Conclusions

SG achieves therapeutically relevant concentrations of SN-38 at 40-fold mean IC50s for GBM, and 150-fold mean IC50s for BCBM. The early intracranial responses are encouraging and will be further evaluated in the Southwest Oncology Group S2007 study.

Clinical trial identification

NCT03995706.

Legal entity responsible for the study

Mays Cancer Center at UT Health San Antonio.

Funding

Mays Cancer Center and Kolitz Endowment.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Mini Oral - CNS Mini Oral session

Invited Discussant 371MO, 372MO and 373MO

Speakers
  • Nicolaus Andratschke (Zurich, Switzerland)
Session Name