Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

ePoster Display

1014P - Characterization of cytokine release syndrome (CRS) following treatment with tebentafusp in previously untreated patients with metastatic uveal melanoma

Date

16 Sep 2021

Session

ePoster Display

Topics

Clinical Research;  Immunotherapy;  Rare Cancers

Tumour Site

Melanoma

Presenters

April Salama

Citation

Annals of Oncology (2021) 32 (suppl_5): S829-S866. 10.1016/annonc/annonc705

Authors

A.K.S. Salama1, V. Cheshuk2, J. Siveke3, A. Berrocal4, S.E. Abdullah5, S. Lockwood6, M.L. McCully7, D. Kee8

Author affiliations

  • 1 Medicine, Duke University, 27710 - Durham/US
  • 2 Chemotherapy, Kyiv City Clinical Oncological Centre, 3115 - Kiev/UA
  • 3 Gastroenterology, Oncology, University Hospital Essen, 45122 - Essen/DE
  • 4 Medical Oncology, Hospital General Universitario Valencia, 46014 - Valencia/ES
  • 5 Clinical Development, Immunocore, 20850 - Rockville/US
  • 6 Biostatistics, Pivotal Statistics Ltd, SK11 6UB - Macclesfield/GB
  • 7 Medical Affairs, Immunocore, OX14 4RY - Abingdon-on-Thames/GB
  • 8 Department Of Cancer Medicine, Peter MacCallum Cancer Center, 3008 - Sydney/AU
More

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.