Abstract 122P
Background
Docetaxel micellar (DM) is a novel formulation of docetaxel, with N-(all-trans-retinoyl)-L-cysteic acid methyl ester sodium salt (XMeNa) as excipient, not requiring pre/post infusional steroids. The study aimed to define safety, preliminary clinical activity and pharmacokinetics (PK) of DM in patients (pts) with mCRPC.
Methods
We enrolled chemotherapy-naïve pts with measurable/evaluable (RECIST1.1/PCWG3 criteria) mCRPC. DM was administered intravenously via a central catheter every 3 weeks at increasing doses (75, 90, 100 mg/m2) following a 3+3 design. No pre/post infusional steroids was given except at cycle 2, to assess for the impact of steroids on docetaxel PK. Pts continued treatment until disease progression or unacceptable toxicity, for a maximum of 10 cycles.
Results
We enrolled a total of 11 pts from 3 Swiss sites between 04/06/2021 and 19/04/2023. Median age was 67 (range 59-75), most frequent sites of metastases were bone (73%) and lymph nodes (55%). Three pts received DM at 75 mg/m2, 3 at 90 mg/m2 and 5 at 100 mg/m2. Median number of treatment cycles was 9 (range 2-10). Dose limiting toxicities (DLT) occurred in 2/11 evaluable pts, both at 100 mg/m2: G4 neutropenia ≥7 days and several G2 non-hematological treatment-related adverse events (TRAE) (nausea, fatigue, diarrhea). Most frequent TRAE of any grade were fatigue (91%), neutropenia (82%), alopecia (64%), diarrhea (54%), leukopenia (54%), peripheral edema (45%) and peripheral sensory neuropathy (46%). G ≥3 TRAE included neutropenia (9 pts), leukopenia (5 pts), anemia and fatigue in 1 patient each. No infusion reaction or febrile neutropenia were reported. Four patients (36%) achieved a PSA response per PCWG3 criteria; 4/9 (44%) evaluable pts had a partial response per RECIST1.1. DM exhibited linear PK with tri-phasic elimination. The clearance was 26.6 L/h, with an inter-individual variability of 20%. No significant impact of steroids on the PKs of DM was found.
Conclusions
DM at a 3-weekly dose of 75 and 90 mg/m2 without steroids has a manageable safety profile. Preliminary clinical activity is as expected for docetaxel in mCRPC. The study was prematurely terminated by the sponsor due to strategic decision and slow recruitment.
Clinical trial identification
NCT04629781.
Editorial acknowledgement
Legal entity responsible for the study
SAKK - Swiss Group for Clinical Cancer Research.
Funding
Vivesto.
Disclosure
I. Colombo: Financial Interests, Institutional, Expert Testimony: GSK, AstraZeneca, AbbVie; Financial Interests, Institutional, Advisory Board: GSK, MSD, AstraZeneca, Incyte; Financial Interests, Personal, Other, Travel grants: GSK; Financial Interests, Personal, Invited Speaker: GSK, MSD, Bayer, Vivesto, Incyte, AstraZeneca, Orion Pharma, Tolremo; Financial Interests, Personal, Other, Health Care Professional Consultancy: BionTech; Financial Interests, Personal, Full or part-time Employment, My husband is an employee of this biomedical company since 02.2022. His role is ‘Marketing Manager’ for the endoscopy division and he is in charge of the launchig program in the field of artificial intelligence applied to colonoscpy. I confirm that his job does not have any conflict of interest with my job and my role at ESMO: Medtronic; Financial Interests, Personal, Stocks/Shares: Medtronic; Non-Financial Interests, Personal, Leadership Role: Swiss Group for Clinical Cancer Research (SAKK); Non-Financial Interests, Personal, Advisory Role: European School of Oncology (ESO). S.C. Fischer: Financial Interests, Institutional, Invited Speaker: Johnson & Johnson, MSD, Astellas; Financial Interests, Institutional, Advisory Board: Ipsen; Other, Personal, Other, Travel support: Bayer. U. Vogl: Financial Interests, Institutional, Advisory Board: Pfizer, Merck, Janssen, Novartis, MSD; Financial Interests, Institutional, Invited Speaker: Astellas, Health Books, Merck, Bayer, Health Books, SAMO; Financial Interests, Institutional, Expert Testimony: Janssen; Financial Interests, Personal, Invited Speaker: Samo, Kantonsspital Chur, Inselspital Bern, Kantonsspital St Gallen; Financial Interests, Institutional, Other, Educational Platform: Oncology Compass; Financial Interests, Institutional, Research Grant: Fond'Action; Non-Financial Interests, Personal, Principal Investigator, Phase III clinical trial: MSD, Gilead; Non-Financial Interests, Personal, Principal Investigator, Phase I study: Amgen; Non-Financial Interests, Personal, Principal Investigator, Phase III study: EORTC. R. Cathomas: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Bayer, MSD, Roche, Astellas, Ipsen, Merck, Pfizer, Accord, Debiopharm; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen, Merck; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Expert Testimony: Sandoz; Non-Financial Interests, Personal, Member of Board of Directors: SAKK Swiss Working Group for Clinical Cancer Research. C. Sessa: Financial Interests, Personal, Other, ESO Consultant for gynaecological cancer: ESO (European School of Oncology); Financial Interests, Personal, Other, DMC member of the MK-3475-C93 studyDMC member of the MK-2870-005 study: Merck; Non-Financial Interests, Personal, Advisory Role, ESMO extended member women for oncology: ESMO; Non-Financial Interests, Personal, Advisory Role, Member of the compliance committee: ESMO. A. Stathis: Financial Interests, Institutional, Expert Testimony: Bayer, Eli Lilly; Financial Interests, Institutional, Advisory Board: Janssen, Roche, Incyte, Beigene; Financial Interests, Institutional, Other, Travel grant: AstraZeneca, Incyte; Financial Interests, Institutional, Other, Consultancy: Debiopharm, AstraZeneca, MSD; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, Merck MSD, Roche, Novartis, ADC Therapeutics, AbbVie, Bayer, Philogen, Cellestia, AstraZeneca, Incyte, Amgen, Loxo Oncology, Debiopharm, BMS. A.G. Omlin: Financial Interests, Institutional, Advisory Board: AstraZeneca, Astellas, Bayer, MSD, Pfizer, Roche, Sanofi, Accord, Advanced Accelerator Applications; Financial Interests, Institutional, Invited Speaker: Monrol. M. Joerger: Financial Interests, Institutional, Invited Speaker, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, Innomedica, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Anaveon; Non-Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. All other authors have declared no conflicts of interest.