Abstract 1014P
Background
Tebentafusp (tebe), a bispecific fusion protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T-cells to target gp100+ cells, has shown an overall survival benefit for patients (pts) with untreated metastatic uveal melanoma (mUM) in a Ph3 trial (NCT03070392). In a post-hoc analysis of a Ph2 trial of 2L+ pts with mUM, mild to moderate episodes of CRS, a cytokine-mediated adverse event (AE), were common following each of the first 3 doses of tebe (Carvajal RD et al. ASCO 2021). Here, we reviewed the incidence, kinetics, and outcome of CRS in tebe-treated pts on the IMCgp100-202 trial of 1L pts with mUM.
Methods
245 HLA-A*02:01+ 1L mUM pts were treated weekly with tebentafusp following intra-patient dose escalation: 20mcg dose 1, 30mcg dose 2 and 68mcg dose 3+. Pts were monitored overnight during escalation to allow management of hypotension and other cytokine-related AEs; prophylactic corticosteroids, antihistamines or acetaminophen were not mandated. CRS was evaluated post-hoc according to ASTCT Consensus Grading criteria (Lee, DW et al. 2019). Analysis was conducted on primary analysis snapshot (Jan 2021).
Results
The most frequent treatment-related AEs, likely cytokine-mediated, included fever (76%), chills (47%), nausea (43%), hypotension (38%). Using ASTCT criteria, 89% of tebe treated pts (n=217) had any grade CRS. Most pts had either grade (G) 1 (12%; n=29) or G2 (76%; n=186), with 2 G3 (0.8%), no G4 and no deaths. Most CRS events occurred within the first 3 doses, reducing in frequency and severity thereafter; 3 episodes of G3 CRS in 2 patients occurred following dose 1, 3 and 4. Only 2 pts discontinued tebe due to CRS (1 G2; 1 G3). Treatment of CRS included antipyretics (n=192), IV fluids (n=93), IV steroids (n=57), oxygen (n=20), and vasopressor use (n=2). Two pts received tocilizumab.
Conclusions
CRS, a common AE observed with T-cell engaging therapies, was frequently observed within 24 hours of initial tebe treatment. Most CRS events were mild or moderate in severity, reversible with standard management strategies, decreased in frequency and severity with subsequent doses, and rarely led to treatment discontinuation.
Clinical trial identification
NCT03070392.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore.
Funding
Immunocore.
Disclosure
A.K.S. Salama: Financial Interests, Institutional, Sponsor/Funding: Immunocore; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Iovance; Financial Interests, Personal, Advisory Role: Regeneron. J. Siveke: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Baxalta; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Shire; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Member of the Board of Directors: Pharma15; Financial Interests, Personal, Other, Equity Holder: FAPI Holding; Financial Interests, Personal, Other, Equity Holder: Pharma15. S.E. Abdullah: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S. Lockwood: Financial Interests, Personal, Other, Consultancy: Immunocore. M.L. McCully: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. All other authors have declared no conflicts of interest.