LTX-315, an oncolytic peptide, to convert immunogenically ‘cold' tumors to ‘hot' in patients with advanced or metastatic tumours: Results from an ongoing phase I study.
2017; Lippincott Williams & Wilkins; Volume: 35; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2017.35.15_suppl.3085
ISSN1527-7755
AutoresJames Spicer, Jean‐François Baurain, Ahmad Awada, Rebecca Kristeleit, Dag Erik Jøssang, Aurélien Marabelle, Delphine Loirat, Hedda Wold, Berit Nicolaisen, Øystein Rekdal, Wenche Marie Olsen, Andrew Saunders, Paal Brunsvig,
Tópico(s)Cancer Immunotherapy and Biomarkers
Resumo3085 Background: Intratumoral LTX-315 disintegrates cytoplasmic organelles with release of tumor antigens in preclinical models accompanied by increase in tumor-infiltrating lymphocytes (TILs). LTX-315 induced complete regression in several rodent models, with systemic immune responses. LTX-315 is strongly synergistic preclinically with immune checkpoint inhibitors (ICI). We are conducting a phase 1 trial to evaluate LTX-315 in combination therapy. Methods: Patients with advanced metastatic solid tumours received injections of LTX-315 into a single accessible tumour over 6 weeks. Additional injections could be administered thereafter every 2 weeks. Biopsies of injected lesions were taken at baseline, and on treatment. Results: 28 have been enrolled to date, median age is 58 (range 32-80) and median prior treatments 2 (range 1-14). LTX-315 monotherapy was administered at doses of 2-7mg to a median of 1.8 tumour lesions (range 1-6) for a median of 9 weeks (range 1-33). In 24 patients all LTX-315-related adverse events were CTC grade 1 or 2, most commonly local erythema, flushing, pruritis and hypotension, most resolving within minutes of injection. Related grade 3 (3 patients) or 4 (1) allergic/anaphylaxis adverse event occurred and resolved without sequelae. Best response in 44 injected lesions in 20 evaluable patients included 2 complete responses, > 50% reduction in 5 tumours, and 20 stable (injected ). Significant increases in TILs occurred in 67% (14 of 21) patients with biopsies of injected tumours available. Regression of distant non-injected tumour has been observed clinically on biopsy (abscopal effect). No irRC response in non-injected tumours has been observed in 16 evaluable patients. Stable disease (median duration 14 weeks) occurred in 50% of patients as best response (melanoma (4), sarcoma (3), breast (1)). Conclusions: This phase 1 study demonstrates that intratumoural LTX-315 has a manageable safety profile and induces increases in TILs in pre-treated patients. Partial and complete regression was seen in some injected tumours. Evaluation of LTX-315 in combination with ICIs in breast and melanoma is ongoing. Clinical trial information: NCT01986426.
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