Abstract 821P
Background
Tebentafusp (tebe) (gp100×CD3) is the first TCR bispecific protein approved for treatment of a solid tumor (metastatic uveal melanoma, mUM). The IMCgp100-202 trial (NCT03070392) in untreated mUM demonstrated improved overall survival, HR=0.51. The most frequent treatment-related AEs (TRAEs), cytokine release syndrome (CRS) and rash, were consistent with mechanism of action and were most common in the first 3 weeks (wks). Once the target dose has been achieved after the first 3 intrapatient escalation doses, tebe is administered as outpatient. After the initial 3 wks, a subset of patients (pts) omitted at least one dose. Here, we assessed the impact on safety and efficacy of dose omissions that occurred beyond the initial 3 doses.
Methods
Planned dosing was 20 mcg (wk1), 30 mcg (wk2), and 68 mcg (wk3+). Omissions were required for certain AEs and also occurred for other elective reasons. Omissions beyond initial 3 wks were analyzed by reason, duration and safety (primarily CRS and rash) within 2 wks of restarting. CRS was evaluated per the ASCTC 2019 criteria. This analysis was conducted on the primary analysis (data cut-off 13Oct2020).
Results
245 pts received tebe; median 23 doses. A total of 104 pts had omissions with 92/245 pts (38%) having an omission after the initial 3 wks. 56/92 pts (61%) had 1 omission; 14 pts had > 3 omissions. Most omissions were due to elective/other reasons (71%) or AEs (29%). 72% of omissions were ≤ 2 wks; 7% of omissions were > 3 wks. Upon restarting, majority of pts did not have G3 TRAE (91%), G2 CRS (93%) or G2+ rash (93%) within 14 days. However, 6 pts had G2 CRS within 14 days of restart and all had prior G2 CRS. 1 or 2 omissions did not have a significant impact on OS when controlling for immortal time bias. The small numbers of pts with omissions > 3 wks duration limit the ability to evaluate impact on OS.
Conclusions
After reaching 68 mcg, patients receiving tebentafusp can have 1-2 omissions of ≤ 2 weeks duration with minimal impact on safety and efficacy. Treatment restart was typically outpatient (95%), without dose modification from most recent dose (98%) or steroid premedication (98%). G2 CRS was uncommon at restart, and occurred mostly in patients with preceding G2 CRS.
Clinical trial identification
NCT03070392.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore Ltd.
Funding
Immunocore Ltd.
Disclosure
M. Schlaak: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Merck/MSD, Roche, Pierre Fabre, Kyowa Kirin, Immunocore, Sanofi Genzyme; Financial Interests, Personal, Other, Travel expenses: Sun Pharma. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer. J.M. Kirkwood: Financial Interests, Personal, Advisory Board, Steering Committee: Amgen Inc; Financial Interests, Personal, Other, Data and Safety Monitoring: Axio Research; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Abstract presentation at SITC: Checkmate Pharmaceuticals; Financial Interests, Personal, Other, Organizer of MRF consensus conference on gene expression profiling with DermTech funds to U PitUPMC: DermTech; Financial Interests, Personal, Other, Consultant: Harbour BioMed, Immunocore, Iovance, Istari Oncology, Natera, Novartis, OncoCyte Corporation, Oncosec Medical, Pfizer, Scopus BioPharma, Takeda Pharmaceutical Company. 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. Milhem: Financial Interests, Personal, Advisory Board: Array BioPharma, Novartis Pharma; Financial Interests, Personal, Other, Consultant: Biontech; Financial Interests, Personal, Other, Steering Committee: Exicure. S. Lockwood: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. C. Hayes: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore; Financial Interests, Personal, Royalties: UptoDate; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Immunocore, Polaris, Xcovery, Pfizer, Novartis, Targovax ASA, Checkmate Pharmaceuticals; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.