TG01 is Targovax’s lead RAS immunotherapy product – a neoantigen therapeutic anti-cancer vaccine targeted at the difficult to treat RAS mutations found in over 90% of pancreatic cancer, 50% of colorectal cancer and 20-30% of all cancers. Initially being tested in the clinic in pancreatic cancer, it is hoped that by inducing mutant RAS specific T-cell immune responses in cancer patients with RAS mutations, TG01 will prolong time to cancer progression, increase survival and improve safety and tolerability compared to chemotherapy and other immunotherapies.
The trial enrolled a total of 32 patients, split in two patient cohorts with 19 patients in the 1st cohort and 13 patients in the 2nd cohort. The cohorts receiving different dosing regimens. Totally 94% of patients (30/32) demonstrated mutant RAS-specific immune activation.
Combining the results from the two cohorts, median overall survival (mOS) for all 32 patients was 33.4 months, which is nearly six months better than the mOS of 27.6 months for gemcitabine alone reported in the recent ESPAC4 trial (Neoptolemos JP et al.; The Lancet; 389:1011-1024 (2017)). Median disease free survival (mDFS) from surgery for the 32 patients was 16.1 months, and 19.5 months for the 2nd patient cohort who received the optimized dosing regimen. This DFS outcome is encouraging when compared to historical controls for gemcitabine monotherapy, such as the ESPAC4 and PRODIGE 24 (J Clin Oncol,36, 2018 (suppl; abstr LBA4001)) trials, which reported a median DFS of around 13 months in similar patient populations.
Summarizing the data from the trial:
mDFS (from surgery):
- First cohort, 19 patients: 13.9 months
- Second cohort, 13 patients: 19.5 months
- Full trial, 32 patients (both cohorts combined): 16.1 months
mOS (from surgery):
- First cohort, 19 patients: 33.1 months
- Second cohort, 13 patients: not yet reached at time of analysis
- Full trial, 32 patients (both cohorts combined): 33.4 months
Patients alive two years after surgery:
- First cohort, 19 patients: 68% (13/19)
- Second cohort, 13 patients: 77% (10/13)
- Full trial, 32 patients (both cohorts combined): 72% (23/32)
TG02, Targovax’s second generation mutRAS neoantigen cancer vaccine, is currently being studied in a Phase 1b clinical trial in colorectal cancer, in combination with the immune checkpoint inhibitor Keytruda. ClinicalTrials.gov Identifier: NCT02933944
Jon Amund Eriksen
Founder of Targovax
Even though RAS mutations were identified as key drivers of cancer progression and treatment resistance several decades ago, effective treatments of RAS-mutated cancers have yet to be made available for patients. We hope that our RAS-targeted immunotherapy will be a practice changing cancer treatment approach.