On November 21, 2018 Lytix Biopharma AS reported its positive top-line data from a Phase 1 study of its first in class oncolytic peptide, LTX-315, administered as monotherapy or in combination with either ipilimumab or pembrolizumab in patients with transdermally accessible tumors (Press release, Lytix Biopharma, NOV 21, 2018, View Source [SID1234531542]).
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The primary objective of the trial was to assess the safety and tolerability of multiple, intratumoral doses of LTX-315 as a monotherapy or in combination. The study comprised four arms (A, B, C and D), with Arms A and B being monotherapy, Arm C recruiting patients with melanoma receiving combination therapy of LTX-315 with intravenous ipilimumab, and Arm D recruiting patients with triple negative breast cancer receiving LTX-315 in combination with intravenous pembrolizumab. The secondary objectives were to evaluate clinical activity and the ability of LTX-315 to evoke immune responses.
The study demonstrated that LTX-315 is safe to administer with manageable toxicities and with no added safety concerns when given in combination, either with ipilimumab or pembrolizumab. One patient in Arm C and two patients in Arm D achieved partial responses (PR). In the monotherapy arms, where paired biopsy samples were available, the study showed that LTX-315 can induce an increase in CD3+ and CD8+ tumour infiltrating lymphocytes (TILS), turn ‘cold’ tumors ‘hot’, and induce T-cell clonal expansion in peripheral blood as well as in tumor tissue.
"Successful completion of the study is an important milestone in the development of LTX-315", said Edwin Klumper, CEO Lytix Biopharma AS. "Demonstration of safety, and the confirmation of the scientific proof of concept with regards to LTX-315’s ability to invoke immune responses was critical to support further development of the compound. The company will now be pursuing the planned strategy of developing LTX-315 as a technology utilised in adoptive transfer of tumor specific T-cells and as a therapeutic in a combination regimen in a number of indications."
"We were encouraged by the experience of working with this novel treatment modality and by the evidence of its safety and early signs of efficacy that this trial demonstrated", said Professor James Spicer, Principal Investigator and Professor of Experimental Cancer Medicine at King’s College Hospital, London.
"This is the first oncolytic peptide that has entered clinical trials. The early indications of efficacy are promising. Intratumoral use of immunotherapies is currently seen as an innovative way to develop synergistic and safe combinations. LTX-315 has the potential to become a simple and universal means to use the tumor as a vaccine and prime the immune response against any cancer type", said Dr Aurelien Marabelle, Study investigator, Clinical Director, Cancer Immunotherapy Program, Gustave Roussy, France and lead author of HIT-IT (Starting the fight in the tumor: Expert recommendations for the development of human intratumoral immunotherapy (HIT-IT))
About the Phase 1 Trial:
The Phase 1 study was a multicentre study, evaluating LTX-315 in a dose ascending manner to assess safety of monotherapy in different dosing regimens (Arms A and B) and selection of a relevant clinical dose for combination with ipilimumab (Arm C) and pembrolizumab (Arm D). The monotherapy arms recruited all advanced cancer types, Arm C recruited patients with advanced melanoma who had prior exposure to anti PD-1 antibody, and Arm D recruited patients with advanced triple negative breast cancer.
In total 65 patients were recruited into this Phase 1 study. Of these, 4 patients in the early monotherapy arms experienced allergic reactions but these were manageable and reversable. Preventative measures were implemented to rectify this by optimising a prophylactic regimen and amending the dosing schedule. Subsequently, no further major allergic reactions were seen. Treatment emergent adverse events were mainly related to injection administration – transient drops in blood pressure, injection site pain and redness, but all toxicities were managed and reversed. Further, there was no evidence that the combination of LTX-315 with either ipilimumab or pembrolizumab conferred additive toxicities, implying that LTX-315 can be used in combination with checkpoint inhibitors without safety concerns.
One patient in Arm C (12.5%) and 2 patients in Arm D (12.5%) achieved a PR. One patient in Arm D had a PR duration of 12 months.
Of those patients in the intent to treat group that provided paired tumour samples, 100% showed an increase in CD3+ lymphocytes and TILs, 80% of tumour biopsies were converted from ‘cold’ to ‘hot’, and 71% showed a statistically significant expansion of peripheral T-cell clones.