Abstract 521P
Background
Tusa (SAR408701) is an antibody-drug conjugate comprised of a cytotoxic maytansinoid linked to a monoclonal antibody that binds to carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5). When given every 2 weeks (Q2W), the tusa maximum tolerated dose (MTD) was 100 mg/m2 and the dose limiting toxicity (DLT) was reversible keratopathy. Here we report dose escalation evaluations of 2 different dosing schedules for tusa.
Methods
Pts with advanced solid tumors were given escalating doses of tusa as a loading dose (LD) on Day 1, Cycle 1 (D1C1) then continued at the confirmed MTD of 100 mg/m2 Q2W or tusa administered on a Q3W schedule. The population was enriched for pts with tumors expressing CEACAM5 (assessed retrospectively in archival tissue). The primary endpoint was incidence of DLTs occurring during weeks 1–4 for LD or weeks 1–3 for Q3W.
Results
The LD group included 28 pts who received tusa at C1 at the dose of 120 (n=3), 135 (4), 150 (8), or 170 mg/m2 (13). The Q3W group included 15 pts who received tusa 120 (n=3), 150 (3), 170 (6) or 190 mg/m2 (3). Median weeks (range) of therapy was 8 (2-32) for LD and 7 (range 3-18) for Q3W. 21 LD pts and all of the Q3W pts were evaluable for DLTs. 2 of 9 DLT evaluable LD pts at 170 mg/m2 had reversible DLTs (G2 keratopathy and G2 keratitis) during C2 and 2 of 3 evaluable Q3W pts at 190mg/m2 had reversible DLTs (Gr 3 transaminase increase and Gr 2 keratopathy) during C1. All LD and Q3W treated pts had treatment emergent adverse events (TEAEs); 13 (46%) LD group and 5 (33%) Q3W group pts had TEAEs that were Gr ≥3. The most frequent TEAEs with the LD were nausea (n=6), asthenia (6), keratopathy (5), and abdominal pain (5). In the Q3W group the most frequent TEAEs were asthenia (n=4), constipation (n=4) and abdominal pain, decreased appetite, keratitis, keratopathy, nausea and peripheral sensory neuropathy (each n=3). Ten (36%) and 6 pts (40%) in the LD and Q3W groups, respectively, had a best overall response of stable disease per RECIST v 1.1.
Conclusions
The MTD of tusa given as an LD or Q3W was 170 mg/m2 for both cohorts. The DLTs, transaminase increase, keratopathy and keratitis, were reversible. Neither group had objective responses.
Clinical trial identification
NCT02187848.
Editorial acknowledgement
Editorial support was provided by Michelle Daniels, MD, inScience Communications, and was funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
J. Tabernero: Financial Interests, Personal, Other, Scientific consultancy role: Array Biopharma; Financial Interests, Personal, Other, Scientific consultancy role: AstraZeneca; Financial Interests, Personal, Other, Scientific consultancy role: Avvinity; Financial Interests, Personal, Other, Scientific consultancy role: Bayer; Financial Interests, Personal, Other, Scientific consultancy role: Boehringer Ingelheim; Financial Interests, Personal, Other, Scientific consultancy role: Chugai; Financial Interests, Personal, Other, Scientific consultancy role: Daiichi Sankyo; Financial Interests, Personal, Other, Scientific consultancy role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Scientific consultancy role: Genentech Inc; Financial Interests, Personal, Other, Scientific consultancy role: HalioDX SAS; Financial Interests, Personal, Other, Scientific consultancy role: Hutchison MediPharma International; Financial Interests, Personal, Other, Scientific consultancy role: Ikena Oncology; Financial Interests, Personal, Other, Scientific consultancy role: IQVIA; Financial Interests, Personal, Other, Scientific consultancy role: Lilly; Financial Interests, Personal, Other, Scientific consultancy role: Menarini; Financial Interests, Personal, Other, Scientific consultancy role: Merck Serono; Financial Interests, Personal, Other, Scientific consultancy role: Merus; Financial Interests, Personal, Other, Scientific consultancy role: MSD; Financial Interests, Personal, Other, Scientific consultancy role: Mirati; Financial Interests, Personal, Other, Scientific consultancy role: Neophore; Financial Interests, Personal, Other, Scientific consultancy role: Novartis; Financial Interests, Personal, Other, Scientific consultancy role: Orion Biotechnology; Financial Interests, Personal, Other, Scientific consultancy role: Peptomyc; Financial Interests, Personal, Other, Scientific consultancy role: Pfizer; Financial Interests, Personal, Other, Scientific consultancy role: Pierre Fabre; Financial Interests, Personal, Other, Scientific consultancy role: Samsung Bioepis; Financial Interests, Personal, Other, Scientific consultancy role: Sanofi; Financial Interests, Personal, Other, Scientific consultancy role: Seattle Genetics; Financial Interests, Personal, Other, Scientific consultancy role: Servier; Financial Interests, Personal, Other, Scientific consultancy role: Taiho; Financial Interests, Personal, Other, Scientific consultancy role: Tessa Therapeutics; Financial Interests, Personal, Other, Scientific consultancy role: TheraMyc; Financial Interests, Personal, Other, Educational collaboration: Imedex; Financial Interests, Personal, Other, Educational collaboration: Medscape Education; Financial Interests, Personal, Other, Educational collaboration: MJH Life Sciences; Financial Interests, Personal, Other, Educational collaboration: PeerView Institute for Medical Education and Physicians Education Resource (PER). P. Bedard: Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: SeaGen; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: SeaGen; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Nektar; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Bicara; Financial Interests, Institutional, Research Grant: Amgen. Y. Bang: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck Serano; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Daiich-Sankyo; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Green Cross; Financial Interests, Personal, Advisory Role: Samyang Biopharm; Financial Interests, Personal, Advisory Role: Hanmi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Serano; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: Green Cross; Financial Interests, Institutional, Research Grant: Genexine.M. Vieito: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Debiopharm; Financial Interests, Personal, Advisory Role: TFS. N. Fagniez: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. S. Yoruk: Financial Interests, Personal, Full or part-time Employment: Sanofi R&D. L. Charbonnier: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. C. Soufflet: Financial Interests, Personal, Full or part-time Employment: Sanofi. N. Masson: Financial Interests, Personal, Full or part-time Employment: Sanofi. All other authors have declared no conflicts of interest.