GBM PAXALISIB ESMO 09/09/2022

Just look at this - and understand why somebody can get rather frustrated here.

Abstract presentation Friday on the paxalisib / GBM study in Paris - at the ESMO Conference.

Check who is doing the presentation on our drug....... John F. De Groot - who is one of the key people running AGM AGILE.

And at the very bottom of these Abstract details - is a news release from Dana Farber (on this, a paxalisib trial run by Kazia). The full news release is show (including the paxalisib paragraph - give you a feel for how paxalisib sits, in the Dana Farber news release)

Dana Farber are selective about any drugs that make it into press realeases....it is not even their Clinical Trial to mention in this news release. But we will take it - With Dr Wen seemingly also part of the presentation at this most prestigious European Conference.

This is very, very good news for pax in GBM. Note some new information being presented - but for John De Groot and Patrick Wen to be so closely involved in a couple days time, still with paxalisib in GBM - well, well well.

Enjoy this news.

---------------------------------------------------------------------------------------------------------------
280O - Pharmacokinetics and pharmacodynamics of paxalisib in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status: Final phase II study results

Presentation Number
280O
Speakers

• John F. De Groot (Houston, United States of America)

Lecture Time
14:50 - 15:00

• Abstract

Background

Paxalisib is being developed for the treatment of glioblastoma multiforme (GBM). Post hoc analysis of phase 1 fluorodeoxyglucose-positron emission tomography (FDG-PET) scans suggested that paxalisib crosses the blood-brain barrier with a uniform distribution throughout the brain.
Methods

The recently completed phase 2 trial (NCT03522298) enrolled patients with newly diagnosed GBM with unmethylated MGMT promoter status following surgical resection and chemotherapy (Stupp Regimen). Study outcomes comprised maximum tolerated dose (MTD), safety, preliminary efficacy, pharmacokinetics (PK) at the MTD under fed and fasted conditions and change in FDG-PET uptake in patients with measurable disease.
Results

Patients (n=30; 70.0% males, mean age 58.5 years) received between 1 and 29 treatment cycles. At the MTD (60 mg/day), paxalisib prolonged median progression free survival (8.4 months [RANO], 8.6 months [mRANO]) and improved median overall survival (15.7 months). Paxalisib was steadily absorbed (median T^max 2.5 and 4 hours postdose) and declined with a mean elimination half-life ranging from 20.2 to 29.0 hours. Mean half-life (20.2 to 29.0 hours) was similar across dose levels and under fed and fasted conditions. Systemic exposure to paxalisib appeared slightly higher for the 60 mg fed status compared to 60 mg fasted status. Comparison of fed versus fasted treatment was statistically significant for C^max at the 90% level (geometric least squares mean ratios: AUC^0-last 1.33, AUC^0-inf 1.06, and C^max 1.52). Ten patients underwent FDG-PET imaging, 8 (80%) had a decrease in FDG uptake on Day 3 and/or Day 7 in Cycle 1 and 4 (40%) had a metabolic partial response.
Conclusions

PK parameters were consistent with prior clinical experience and there was no evidence of a deviation from dose-proportionality. At the MTD FDG-PET data provide evidence that paxalisib has the ability to exert biological effect in tumour tissue, irrespective of fed or fasted status. Further evaluation is ongoing in GBM AGILE (NCT03970447).





----------------------------------------------------------------------------------------------------------------------------------------------------

NEWS RELEASE 6-SEP-2022
Data from pivotal breast cancer and kidney cancer studies headline Dana-Farber research presented at ESMO Congress 2022

Reports and Proceedings
DANA-FARBER CANCER INSTITUTE

PrintEmail App
Combination therapies show encouraging results in several studies led by Dana-Farber Cancer Institute and presented for the first time at the European Society of Medical Oncology (ESMO) Congress 2022, Paris, France. The studies will be presented both in-person and online on September 9-13, 2022.
Dana-Farber’s Toni Choueiri, MD, director of the Lank Center for Genitourinary Cancer, will present results of a phase 3 study looking at a three-drug regimen (cabozantinib, nivolumab, and ipilimumab) in patients with previously untreated advanced kidney cancer (LBA8). The first findings from COSMIC-313 will be presented during the Presidential Symposium on Monday, September 12, 2022, 10:30am ET (16:30 CEST) and featured among the ESMO PR program. The presidential sessions feature oral presentations by authors presenting cutting-edge and significant clinical practice-changing studies.
A pivotal breast cancer study (LBA18) led by Dana-Farber’s Sara Tolaney, MD, MPH, looking at a combination therapy in patients with HR+, HER2+ advanced breast cancer will be presented as a late-breaking abstract in the Mini Oral session: Breast cancer, metastatic on Saturday, September 10, 8:45am ET (14:45 CEST). Data from the phase 2 monarcHER study evaluating overall survival of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard of care will be presented.
Also featured in this year’s ESMO PR program, the results of the PATHFINDER study (903O), conducted by researchers at Dana-Farber. PATHFINDER examined if a simple blood test could detect a cancer signal in people aged 50 years and older who were not known to have cancer. The results could be an important first step for early cancer detection tests. Data from the PATHFINDER study will be shared during the Proffered Paper session: Basic science & translational research on Sunday, September 11, 10:30am ET (16:30 CEST).
Other key research from Dana-Farber faculty shows new treatments and diagnostic advances in brain cancer, kidney cancer, oral cancer, and many others. Select studies include:

--------------------------------------------------------------------------------------------------
Glioblastoma treatment prolongs progression free survival, improves overall survival
Glioblastoma is an aggressive, deadly, and treatment-resistant type of malignant brain tumor, with few treatment options available. In this phase 2 study, led by Dana-Farber’s Patrick Wen, MD, director of the center for Neuro-Oncology, researchers found paxalisib can exert biologic effect in tumor tissue, irrespective of fed or fasted status. The study looked at newly diagnosed patients with glioblastoma with unmethylated MGMT promotor status. The data shows at the maximum tolerated dose, paxalisib prolonged median progression free survival (8.4 months [RANO], 8.6 months [mRANO]) and improved median overall survival (15.7 months).
Title/Abstract:  Pharmacokinetics and pharmacodynamics of paxalisib in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status: Final Phase 2 study results (Abstract 280O)

• Lead Author: Patrick Wen, MD
• Proffered Paper Session: Central Nervous System Tumors, Friday, September 9, 2022, 8:50am ET (14:50 CEST)

--------------------------------------------------------------------------------------------------------

Immunotherapy effective in high-risk oral precancerous disease
Oral proliferative leukoplakia is an aggressive precancerous disease marked by multifocal lesions and a high-risk of progressing to oral squamous cell carcinoma. There are currently no effective treatments to prevent progression to oral cancer. In this phase 2 study, presented by Dana-Farber’s Glenn Hanna, MD, director of the Center for Salivary and Rare Head and Neck Cancers, researchers found 37% of patients with high-risk oral leukoplakia treated with nivolumab had proliferative leukoplakia regression, and demonstrated favorable overall cancer-free survival. This is the first study to demonstrate evidence of efficacy using preventative immunotherapy for high-risk oral precancerous disease.
Title/Abstract: A phase 2 study of nivolumab for high-risk oral leukoplakia (Abstract 650O)

• Presenter: Glenn Hanna, MD
• Proffered Paper Session: Head and Neck Cancer, Monday, September 12, 2022, 8:45 ET (14:45 CEST)

Combination therapy shows promising antitumor activity in advanced untreated kidney cancer
For patients with advanced renal cell carcinoma (kidney cancer), treatment with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) has improved outcomes, but most patients eventually experience disease progression. In this open-label phase 2 study, led by Dana-Farber’s Toni Choueiri, MD, researchers investigated the combination of cabozantinib, a VEGF TKI, plus belzutifan, a HIF-2α inhibitor. Belzutifan has shown antitumor activity and favorable safety in heavily pretreated advanced kidney cancer. Patients in the study were diagnosed with advanced clear cell renal cell carcinoma and had received no previous treatment. The analysis presented at ESMO is the first data from cohort 1 of the LITESPARK-003 trial. After a median follow-up of 14 months, interim results of the combination show promising antitumor activity. Overall objective response rate (ORR) was 57% and the combination had manageable safety
Title/Abstract: Phase 2 study of belzutifan plus cabozantinib as first-line treatment of advanced renal cell carcinoma (RCC): Cohort 1 of LITESPARK-003 (Abstract 1447O)

• Lead Author: Toni Choueiri, MD
• Proffered Paper Session: Genitourinary Tumors, non-prostate, Monday, September 12, 2022, 9:30am ET (15:30 CEST)

Dana-Farber research included in Mini Oral sessions includes:
Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2– metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase 3 TROPiCS-02 study (Abstract 214MO)

• Lead author: Sara Tolaney, MD
• Mini Oral Abstract Session: Breast Cancer, metastatic, Saturday, September 10, 2022, 9:40am ET (15:40 CEST)

AMEERA-3, a Phase 2 study of amcenestrant (AMC) versus endocrine treatment of physician’s choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC) (Abstract 212MO)

• Presenter: Sara Tolaney, MD
• Mini Oral Abstract Session: Breast Cancer, metastatic, Saturday, September 10, 2022, 9:15am ET (15:15 CEST)

A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients with advanced solid tumors (Abstract 731MO)

• Presenter: Glenn Hanna, MD
• Mini Oral Abstract Session: Investigational immunotherapy, Saturday, September 10, 2022, 8:55am ET (14:55 CEST)

Updated efficacy of lenvatinib (LEN) + pembrolizumab (PEMBRO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in the CLEAR study (Abstract 1449MO)

• Lead Author: Toni Choueiri, MD
• Mini Oral Abstract Session: Genitourinary tumors, non-prostate, Sunday, September 11, 2022, 8:45am ET (14:45 CEST)

In-situ immune markers predict nivolumab (N) +/-ipilimumab (I) efficacy in frontline metastatic clear cell renal cell carcinoma (mccRCC): key ancillary analyses from the BIONIKK randomized trial. (Abstract 1451MO)

• Presenter: Maxime Meylan, PhD
• Mini Oral Abstract Session: Genitourinary tumors, non-prostate, Monday, September 12, 2022, 2:30am ET (8:30 CEST)

For all ESMO-related media inquiries, call or email Victoria Warren, 617-939-5531, [email protected]. Follow the meeting live on Twitter using the hashtag #ESMO22 and follow Dana-Farber News on Twitter at @DanaFarberNews.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is one of t