Abstract 873P
Background
LN-145, an ex vivo expanded autologous TIL product, demonstrates efficacy in patients with advanced cervical cancer in study C-145-04, with 44% ORR and 85% DCR. Here, we characterized the clonal composition of LN-145 infusion products, the in vivo fate of TIL clones, and asked how they related to clinical response, persistence of TIL in patients, and HPV reactivity.
Methods
LN-145 TIL products from 27 patients were subjected to CDR3 RNA-seq to establish a repertoire that was then monitored in pre- and post-infusion PBMC for each patient. Known statistical methods were used to determine clonal diversity, overlap across samples, and correlations to clinical response and HPV reactivity as assessed by co-culturing with peptide-loaded autologous APC.
Results
Number of unique TIL clones and corresponding diversity indices averaged 25,222 [3,829-87,751] and 7.83 [4.7-11.4], respectively, and distributed along a head and tail curve with 10 most abundant clones representing ∼42% of the total repertoires. Less than 1% of clones were detected in more than 3 of the 27 patients. TIL-derived clones persisted at all post-infusion timepoints. A mean of 2043 clones were shared at D42, representing 11% and 20% of LN-145 and PBMC clones, respectively, and a substantial portion of the total TIL (66%) and D42 (57%) repertoires. Clonal persistence did not predict the clinical response. No correlation was found between HPV reactivity and response. As many as 47% of the TIL products did not react to HPV.
Conclusions
LN-145 is a highly polyclonal and patient-specific product endowed with in vivo persistence ability. The uniqueness of each TIL product and observation of responses with HPV non-reactive TIL highlights the challenge of identifying a single TCR as a common mediator of activity and supports using LN-145 to treat solid tumors with their associated private neoantigen spectra.
Clinical trial identification
NCT03108495.
Editorial acknowledgement
Legal entity responsible for the study
Iovance Biotherapeutics, Inc.
Funding
Iovance Biotherapeutics, Inc.
Disclosure
Jazaeri: Research grant/Funding (institution): Iovance; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): AZ; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: NuProbe; Advisory/Consultancy: AvengeBio; Advisory/Consultancy: GLG; Advisory/Consultancy: Guidepoint. V. Gontcharova, M. Blaskovich, E. Masteller, C. Chartier: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance Biotherapeutics, Inc. K. Kunkalla: Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance Biotherapeutics, Inc. M. Fardis: Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: Iovance Biotherapeutics, Inc.; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: AbbVie; Officer/Board of Directors: Kartos Therapeutics.