454P - Tetrahydrocannabinol (THC) / cannabidiol (CBD) oral solution in combination with temozolomide (TMZ) and radiotherapy (RT) in patients with newly diagnosed glioblastoma: Phase Ib GEINO-1601 trial

Background

Resistance to front-line TMZ is a common treatment complication for patients (pts) with glioblastoma (GBM). THC / CBD enhance autophagy and apoptosis when combined with TMZ in preclinical models of GBM and may overcome TMZ resistance in GBM.

Methods

GEINO-1601 is an open-label, single arm, phase Ib trial in Spain including pts with newly diagnosed GBM, aged ≥18 years and ≤70 years to evaluate the association of cannabinoids with RT / TMZ. THC / CBD 10 mg/ml each as oral solution is administered continuously in combination with RT / TMZ and 6 cycles of TMZ (Stupp scheme) followed by maintenance with THC / CBD monotherapy. Pts receive 5 mg / day during week 1 and intra-pts doses are escalated weekly up to 80 mg / day. Self-titrated dose escalation is stopped in case of toxicity or bad tolerance. Pts with psychiatric, psychotic or cognitive disorders, cardiovascular diseases and those previously exposed to cannabis were excluded. The study planned to include 30 pts. The primary objective is to determine the maximum tolerated dose of THC / CBD according to NCI CTCAE V5.0. Secondary objectives include antitumor activity and translational research. This abstract focuses on the safety profile and treatment compliance after accrual is completed.

Results

From Sep 2023 to Apr 2024, 33 pts were included, 29 received THC / CBD. The median age was 61 years (range: 28-71). Most were female (55%). The self-titrated dose escalation is underway and the maximum dose was already reached in 22 pts after a median follow-up of 7.4 m (95% CI: 4-8.1). The maximum pre-specified dose of 80 mg / day was reached by 11 (38%) pts. Serious adverse events (AEs) related to study treatments were reported in 1 pts (3.4%), who experienced G4 neutropenia and thrombocytopenia related to TMZ. G3-4 AEs were hematologic events (13.8%), and alopecia (3.4%). No G3-4 AEs related to THC / CBD were reported. G1-2 AEs related to THC / CBD occurred in 25 pts, most frequent asthenia (37.9%), nausea (37.9%), somnolence (34.5%), vomiting (17.2%) and dizziness (13.8%), showing dose dependency.

Conclusions

Accrual has been completed and THC / CBD oral solution combined with Stupp scheme is being administered safely in pts with GBM.

Clinical trial identification

EudraCT: 2016-003216-12 / NCT03529448.

Editorial acknowledgement

We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.

Legal entity responsible for the study

Grupo Español de Investigación en Neurooncología (GEINO).

Funding

Grupo Español de Investigación en Neurooncología (GEINO) through The Cannabis Bike Tour that awarded a grant for the conduct of this study and industry partner Tilray, that provided the experimental treatment.

Disclosure

J.M. Sepúlveda: Financial Interests, Personal, Speaker, Consultant, Advisor: CANTEX pharma, BMS, GSK, GW Pharma; Financial Interests, Personal, Advisory Board: Servier, Novocure, BMS, MSD, GSK; Financial Interests, Personal, Speaker’s Bureau: Novocure, GSK; Financial Interests, Personal, Project Lead: Tilray Pharma, Pfizer. G. Velilla: Financial Interests, Personal, Invited Speaker: Neuraxpharm. M. Martínez-García: Financial Interests, Personal, Speaker’s Bureau: Novocure; Financial Interests, Personal, Advisory Role: Novocure, Boehringer Ingelheim, Eli Lilly, Seagen; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria, Travel accommodation expenses: AstraZeneca, Gilead, Pfizer; Financial Interests, Personal, Other, Travel accommodation expenses: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria (public speaking): Reddy Pharma. A. Stradella: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Seagen, Boehringer Ingelheim, Gilead; Financial Interests, Personal, Speaker’s Bureau: Daiichi, Novartis, Gilead, AstraZeneca; Financial Interests, Personal, Other, travel/accommodation expenses: Pfizer, Novartis, Eisai; Financial Interests, Personal, Member of Board of Directors, GEICAM executive board: GEICAM. P. Sàbat Viltró: Other, Personal, Other, Training: Lilly. M. Guzmán: Financial Interests, Personal, Expert Testimony: Zelda Therapeutics; Financial Interests, Personal, Leadership Role, Member of the Medical advisory board: Zelda Therapeutics, Fundación Canna; Financial Interests, Institutional, Research Funding, Research contract to study the antitumoral effect of cannabinoids in breast cancer: Zelda Therapeutics; Other, Personal, Member of Board of Directors, Vicepresident: OECM; Financial Interests, Personal, Leadership Role, President of the International Association for Cannabinoid Medicines: IACM; Financial Interests, Personal, Principal Investigator: UCM, CIBERNED, IRYCIS, IUIN. All other authors have declared no conflicts of interest.