500O - Trotabresib (CC-90010) combined with concomitant temozolomide (TMZ) plus radiotherapy (RT) and adjuvant TMZ in patients (pts) with newly diagnosed primary glioblastoma (ndGBM): Updated results from a phase Ib/II study

Background

Trotabresib (TROTA) is a novel bromodomain and extraterminal protein inhibitor that has shown brain tumor tissue penetration, encouraging tolerability and preliminary efficacy in combination with standard of care (SOC) concomitant TMZ + RT and adjuvant TMZ in pts with ndGBM. We present long-term follow-up for part A (dose escalation) and an update on part B (expansion) of the ph 1b/2 CC-90010-GBM-002 study (NCT04324840).

Methods

Study design has been previously described (Vieito et al. SNO 2022 . Abstr CTNI-21). Part B enrolled pts with IDH wild-type ndGBM; pts were randomized 2:1 to TROTA + SOC then maintenance TROTA (arm A) vs SOC alone (arm B).

Results

As of 20 Jan 2023, part A has closed with 32 pts enrolled (concomitant, n = 14; adjuvant, n = 18); part B has enrolled 136 pts (arm A, n = 91; arm B, n = 45). In part A, no new safety events were observed with longer follow-up; median follow-up was 21.6 mo (range 3.4–27.6). The most frequent grade (G) 3/4 treatment-related adverse event (TRAE) was thrombocytopenia (8/14 pts [57%] in the concomitant group and 9/18 pts [50%] in the adjuvant group). Efficacy in part A is shown in the table. At last follow-up, 8 pts (4 per group) remained on treatment, including 1 pt with ongoing complete response at cycle 24. In part B, the most common all-cause G 3/4 AE was thrombocytopenia occurring in 21/88 (24%) and 5/43 (12%) patients in arms A and B, respectively. TRAEs related to TROTA led to treatment discontinuation in 3 pts (arm A), and TRAEs related to TMZ led to discontinuation in 4 pts (2 in each arm); no treatment-related deaths reported. Enrollment of part B was recently completed; efficacy data are not yet mature.

Conclusions

Addition of TROTA to SOC followed by maintenance TROTA in pts with ndGBM was well tolerated with no new safety signals in parts A and B, and promising efficacy in part A. Follow-up is ongoing.

Table: 500O

*Administered on days 1–4 of each 28-day cycle. 30 mg/day is the recommended phase 2 dose. NE, not estimable; OS, overall survival; PFS, progression-free survival.

Clinical trial identification

NCT04324840.

Editorial acknowledgement

Writing and editorial support were provided by Benjamin Levine, PhD, and Agata Shodeke, PhD of Spark Medica Inc, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

M. Vieito Villar: Non-Financial Interests, Principal Investigator: Roche, Bristol Myers Squibb, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. J.M. Sepúlveda Sánchez: Financial Interests, Personal, Advisory Board: Cantex, CeCaVa, MSD, Novocure; Financial Interests, Personal, Invited Speaker: GSK; Non-Financial Interests, Personal and Institutional, Research Grant: Cantex, Pfizer. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, Bristol Myers Squibb, Boehringer, Boheringer, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith: Multiple. G. Lombardi: Financial Interests, Personal, Advisory Board: Janssen, Braun, Helath4U; Financial Interests, Personal, Invited Speaker: Bayer, Orbus, Novartis; Financial Interests, Institutional, Coordinating PI: Bayer SpA. A. Stradella: Financial Interests, Personal, Advisory Board, Advisory about CAPITELLO 291 trial: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory on new activities for residents: Novartis; Financial Interests, Personal, Invited Speaker, Trastu-Deruxtecan clinical case meeting: Daiichi; Financial Interests, Personal, Invited Speaker, meeting on new data on cyclin inhibitors: Novartis. C.A. Haslund: Financial Interests, Personal, Invited Speaker: MSD, GSK, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Tesaro, MSD, IO Biotech, Chimerix, Incyte; Financial Interests, Institutional, Coordinating PI: GSK, Celgene Aps. E. Pineda: Financial Interests, Personal, Advisory Board: Novocure. F.Y.F.L. De Vos: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Novartis, GSK, Bristol Meyers Squibb; Non-Financial Interests, Member of Board of Directors, Dutch Society of Medical Experts Treating Rare Cancers: Dutch Rare Cancer Platform; Non-Financial Interests, Leadership Role, Chair Quality of Care Committee: Dutch Society of Medical Oncology; Non-Financial Interests, Leadership Role, board member of Quality Assurance in Brain Tumor Group: European Organisation for Research and Treatment of Cancer; Non-Financial Interests, , Member of Board of Directors, national databank on care in brain tumor patients: Dutch Brain Tumor Registry; Non-Financial Interests, Leadership Role, board member of Education Committee: European Association for Neuro-Oncology; Other, grant for research project given bij non-profit patient advocacy group: Foundation STOPBraintumors.org. M.A. Vaz Salgado: Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal and Institutional, Coordinating PI: Pfizer. M. Martinez Garcia: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Takeda, Seagen, Pierre Fabre, Novocure; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer, Daiichi Sankyo, AstraZeneca, Gilead; Non-Financial Interests, Leadership Role, Member of the board: GEINO, Spanish group of Neuro Oncology; Non-Financial Interests, Principal Investigator, Clinical Trials: Bristol Myers Squibb Celgene, Roche; Non-Financial Interests, Principal Investigator, Clinical trial: Cantargia; Non-Financial Interests, Principal Investigator, Clinical Trial: Laminar Pharma; Non-Financial Interests, , Principal Investigator, clinical trial: Incyte. T. Sanchez: Financial Interests, Personal, Full or part-time Employment, I work as Clinical Scientist for Bristol Myers Squibb: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares, I own some shares in Bristol Myers Squibb: Bristol Myers Squibb. B. Hanna: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. X. Li: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. Z. Nikolova: Financial Interests, Institutional, Full or part-time Employment, I am full time employee of Bristol Myers Squibb and possess shares: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb; Non-Financial Interests, Project Lead, Clinical Leader for MoCR TRC: Bristol Myers Squibb. M. Simonelli: Financial Interests, Personal, Advisory Board: Incyte, Cytovia; Financial Interests, Personal, Invited Speaker: GSK, Bristol Myers Squibb; Financial Interests, Personal, Other, Data Monitoring Committee: Sanofi. All other authors have declared no conflicts of interest.