Abstract 1403P
Background
Dendrimers enable sustained delivery of cytotoxic drugs and achieve selective tumour targeting via an enhanced permeability and retention effect. DEP cabazitaxel is a lysine-based dendrimer modified with polyethylene glycol and with cabazitaxel attached to lysine branches via a hydrolysable linker. Unlike standard cabazitaxel, DEP cabazitaxel is highly water soluble, does not contain toxic excipients associated with anaphylaxis and avoids the need for steroid pre-medication. Safety and preliminary efficacy of DEP cabazitaxel was assessed in a phase 1/2 trial of with patients (pts) with advanced solid tumours, including mCRPC.
Methods
3-weekly intravenous dosing of pts was escalated to study the safety profile and identify a recommended phase 2 dose (RP2D) for an expansion cohort. Eligible prostate pts had one or more of rising PSA, measurable disease progression, or bone progression per Prostate Cancer Working Group 3 (PCWG3) guidelines. Anti-tumour activity was assessed using these 3 PCWG3 criteria.
Results
A RP2D of 20 mg/m2 cabazitaxel was confirmed; 2 Dose Limiting Toxicities of Grade 3 febrile neutropenia and grade 4 neutropenia > 7 days were observed. Most common toxicities were Grade 1/2 and those typically observed with standard cabazitaxel. There was no neutropenic sepsis or anaphylaxis. 25 mCRPC pts were enrolled at the RP2D; median age of 73 yrs and with an average 4 prior anticancer treatments, including taxanes. Responses were seen in one or more of the efficacy outcomes for all (100%) evaluable mCRPC pts. Of those evaluable for all PCWG3 criteria 56% responded in all three. In pts with soft tissue lesions, 64% had prolonged disease control, including 2 partial responses sustained for up ≥24 weeks. Of pts with assessable PSA, 90% had a reduction, with a response of >50% in 52%. Of pts with bone metastases, 83% had no progression or an improvement.
Conclusions
DEP cabazitaxel is well tolerated with rates of severe myelosuppression, including neutropenia, lower than published data for standard cabazitaxel. No steroid pre-medication was required. We report encouraging anti-tumour activity in heavily pre-treated mCRPC pts.
Clinical trial identification
Protocol number: CTX-SPL9111-001; EudraCT number: 2017-003424-76.
Editorial acknowledgement
Legal entity responsible for the study
Starpharma Pty Ltd.
Funding
Starpharma Pty Ltd.
Disclosure
R.H. Jones: Financial Interests, Institutional, Other, Access to trial data owned by NHS Sponsor: AZ; Financial Interests, Institutional, Invited Speaker, participation in commercial trial: Roche, Genentech, Bayer, Orion, Starpharma, Genmab, G1 Therapeutics, Sanofi, H3 Biomedicine, BioNTech, Boehringer, BMS. D.J. Pinato: Financial Interests, Personal, Advisory Board: Mina Therapeutics, EISAI, Exact Sciences, MURSLA, H3B, DaVolterra, AstraZeneca, Bayer Healthcare; Financial Interests, Personal, Invited Speaker: BMS, Ipsen, Roche; Financial Interests, Personal, Other, Editor in Chief role: Wiley; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Principal Investigator: Incyte, H3B, Starpharma, Roche, Ribon Therapeutics, Turning Point Therapeutics, Apollomics; Non-Financial Interests, Other, Charity Trustee: Cancer Treatment and Research Trust. A. Joshua: Financial Interests, Personal, Stocks/Shares: Pricillium Therapeutics; Financial Interests, Institutional, Invited Speaker: Neolukin, Janssen, Ipsen, AstraZeneca, Sanofi, Noxopharm, Iqvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, Janssen, Merck, Mayne, Roche, Bayer, Macrogenics, Pfizer, AstraZeneca, Corvus, Eli Lilly. M.D. Forster: Financial Interests, Personal, Advisory Board: bayer, Merck, MSD, Novartis, roche, Takeda, ultrahuman, Transgene, Ixogen, Immunotep; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Invited Speaker: StarPharma, Roche. K. Aboud: Financial Interests, Institutional, Other, CTX trial at Velindre NHS trust site is sponsored by Starpharma. I am a sub-investigator on CTX trial and employed by the NHS (National Health Service) and have no direct financial or personal interest with Starpharma: Starpharma. S. Edmondson: Financial Interests, Personal, Full or part-time Employment: Starpharma Pty Ltd.; Financial Interests, Personal, Stocks/Shares: Starpharma Pty Ltd.; Non-Financial Interests, Member: American Society of Clinical Oncology, ARCS Australia Ltd. N.J. Main: Financial Interests, Personal, Full or part-time Employment, Clinical Development Manager: Starpharma Holdings Limited (SPL); Financial Interests, Personal, Stocks/Shares, Employee Incentive Scheme: Starpharma Holdings Limited (SPL). J.R.A. Paull: Financial Interests, Personal, Full or part-time Employment: Starpharma Pty Ltd.; Financial Interests, Personal, Stocks/Shares: Starpharma Holdings Ltd. J.K. Fairley: Financial Interests, Personal, Other, Executive Role: Starpharma; Financial Interests, Personal, Full or part-time Employment, CEO: Starpharma; Financial Interests, Personal, Stocks/Shares, Shares owned: Starpharma. J. Spicer: Financial Interests, Institutional, Advisory Board: Lilly, AstraZeneca, Boehringer Ingelheim, BMS, Genmab, GSK, RS Oncology, Seattle Genetics, Merck; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Institutional, Invited Speaker: Achilles, Genmab, Roche, Seattle Genetics, Starpharma, Trizell, BergenBio, BMS, IO Biotech, MSD; Non-Financial Interests, Invited Speaker, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Invited Speaker, Steering Committee: British Thoracic Oncology Group. All other authors have declared no conflicts of interest.