392P - Updated data of biodistribution and activity of oncolytic virus TG6002 after intravenous administration in patients with advanced gastrointestinal carcinomas

Background

In a report on 15 pts included in TG6002.02 dose-escalation trial (ESMO 2021, Abstract #3550), we showed that TG6002, an oncolytic vaccinia virus deleted in 2 genes to selectively replicate in tumor cells and encoding FCU1, an enzyme converting 5-FC into 5-FU, was biodistributed and replicated in tumor tissue after IV administration and expressed a functional payload. Herein, we report the data with 15 additional pts treated with either higher doses of TG6002 or a more intensive schedule of administration.

Methods

30 pts (med age 61.5 years) received TG6002 either on days 1, 8 and 15 at the dose of 3x10⁸ (n=3), 1x10⁹ (n=10) or 3x10⁹ pfu (n=8) combined with oral 5-FC on days 5-7, 12-14, and 19-28 (Arm A), or on days 1, 3 and 5 at the dose of 1x10⁹ pfu (n=9) combined with 5-FC on days 9-18 (Arm B). Blood was sampled 30 min, 1h, 3h and 24h after the first and the third infusion for plasma TG6002 PK and on days 5, 7, 14 and 28 for serum 5-FC and 5-FU measurements. Sampling of a tumor lesion was performed on day 5 (Arm A) or day 9 (Arm B) along with blood sampling for virus detection by qPCR and plaque assay, and 5-FC and 5-FU quantification.

Results

TG6002 was cleared from plasma within 3 hours with no difference across days of dosing, dose levels, or study arm. On day 5, TG6002 was detected in tumor in 1/3, 3/8 and 2/7 patients in the 3x10⁸, 1x10⁹ and 3x10⁹ pfu cohorts, respectively, and in 4/7 pts in arm B. FCU1 activity, as measured by 5-FU concentration in plasma and in biopsy specimens, suggested that the virus was active in all pts, even in those without virus detection in tumors. Levels of 5-FU in plasma correlated with 5-FU concentration in tumors and highest levels were observed in pts with detectable viral genome in biopsies. This correlation suggests that FCU1 activity is localized in cancer cells and support the tumor selectivity of TG6002. In terms of safety, a single dose-limiting toxicity was observed among these 30 pts consisting of a disseminated pustular rash in one pt treated at the dose of 3x10⁹ pfu.

Conclusions

The updated data of TG6002.02 trial at higher doses of TG6002 confirmed the favourable safety profile of the TG6002/5-FC combination and the effective expression of the FCU1 transgene in tumor cells.

Clinical trial identification

Eudract N° 2018-000039-28.

Editorial acknowledgement

Legal entity responsible for the study

TRANSGENE S.A.

Funding

TRANSGENE S.A.

Disclosure

All authors have declared no conflicts of interest.