Results of a first-in-human phase I study of INVAC-1, an optimized plasmid DNA encoding an inactive form of human telomerase reverse transcriptase (hTERT), in patients with advanced solid tumors.

3087 Background: INVAC-1 is an optimized plasmid encoding an inactive form of human telomerase reverse transcriptase (hTERT). hTERT is a prototype of shared tumor antigen expressed in more than 85% of human tumors. Telomerase activation is associated with maintenance of telomere length and accounts for the unlimited proliferative capacity of cancer cells. In preclinical models, INVAC-1 triggered Th1-polarized hTERT-specific CD8+ and CD4+T-cell immune responses and anti-tumor effects. Here, we report clinical and pharmacodynamics results of the first clinical study with INVAC-1 as a single agent in solid tumors. Methods: A 3+3 design phase 1 First in Human study evaluating INVAC-1 given monthly for 3 cycles using electroporation-based intra-dermal (ID) injection was conducted. Primary objectives included safety, tolerability and dose limiting toxicities to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives included immune response and anti-tumor activity. Results: 20 patients (pts) with refractory/progressive solid tumors were enrolled in two centers. 3 escalating doses were studied: 100 µg (3 pts), 400 µg (3 pts) and 800 µg (14 pts). At 3-month data cut-off, no dose limiting toxicities or treatment related SAEs have been reported; no MTD was defined. The most common treatment-related adverse events were grade 1 or 2: asthenia and local reaction at injection site. 12 pts experienced stable disease and clinical benefit. For 10 pts, the treatment was extended beyond the per-protocol 3-month duration, up to nine months for 2 pts. IFN-g polarized anti-hTERT immune responses were detected in 55% of pts, in response to INVAC-1 treatment. Conclusions: Results from this study indicate that INVAC-1 ID was safe, well tolerated and strongly immunogenic at the doses and schedule tested. Early anti-tumor activity has been observed. The RP2D of INVAC-1 is therefore a monthly ID injection of 800 µg. These results encourage a future evaluation of INVAC-1 is solid tumors, as well as in hematologic malignancies, either as monotherapy or in combination with various immunotherapeutic drugs. Clinical trial information: NCT02301754.