652O - Randomized phase III VANCE study: Gemcitabine and carboplatin (GC) followed by Epstein Barr virus-specific autologous cytotoxic T lymphocytes (EBV-CTL) versus the same chemotherapy as first-line treatment for advanced nasopharyngeal carcinoma (NPC)

Background

The VANCE trial (NCT 20578641) is the largest clinical trial of adoptive T cell therapy in solid tumors. This phase III, multicenter, randomized, open-label study evaluates the efficacy of GC followed by EBV-CTL versus GC alone as first-line treatment for locally recurrent but incurable and metastatic NPC (R/M). EBV-CTL is an autologous T-cell immunotherapy generated from blood of the patient and manufactured without genetic modification. Thirty clinical trial sites involved were from USA, Singapore, Malaysia, Taiwan and Thailand.

Methods

Patients with R/M NPC were randomized to Arm A (GC x 4 cycles and EBV-CTL x up to 6 cycles) or Arm B (GC x 6 cycles) in a 1:1 ratio. Primary Objective is to assess Overall Survival (OS) of EBV-CTL following GC compared to GC.

Results

Of 330 randomized patients, 164 were enrolled in Arm A and 166 in Arm B. 325 patients were treated including 133 patients treated with EBV-CTL. The central Good Manufacturing Practice (GMP) facility was able to produce sufficient EBV-CTL for 94% of Arm A patients. Demographics and baseline characteristics were balanced. Median age was 54 (21-80) years, 75.2% were male, 97% were Asian, 43.6% had an ECOG PS of 1. 65.2% of Arm A and 66.3% in Arm B had prior radiation/chemoRT for earlier locoregional NPC. Patients who completed 4 cycles of GC were 82.3 % in Arm A, and 82.5 % in Arm B (58.4% completed 6 cycles). 80.5% of patients in Arm A received at least two infusions of EBV-CTL. Median dose per cycle was 4.5 × 10⁸ cells/m². The median OS was 25.0 months (19.7-31.8) in Arm A and 24.9 months (19.7-32.8) in Arm B (hazard ratio [HR] 1.19; p = 0.1942). Secondary endpoints of PFS and ORR will be available at time of ESMO Congress 2022. 87.7% of patients had grade 3 or higher adverse events (AE) (85.0% in Arm A, 89.6% in Arm B). Thirteen out of 133 patients treated with EBV-CTL (9.8%) experienced EBV-CTL related AEs, all grade 1 and 2, except two grade 3 events of anemia and leukopenia that occurred in one patient.

Conclusions

EBV-CTL as first-line treatment in patients with R/M NPC had a favorable safety profile but did not demonstrate a longer OS vs standard of care (SOC) chemotherapy.

Clinical trial identification

Protocol number: FF01; latest protocol release date: 1 May 2020 and 31 Jul 2020.

Editorial acknowledgement

Authors on behalf of VANCE trial investigators.

Legal entity responsible for the study

Tessa Therapeutics Ltd.

Funding

Tessa Therapeutics Ltd.

Disclosure

H.C. Toh: Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Advisory Board, Liver Cancer Global SAB in 2022: AstraZeneca; Financial Interests, Personal, Full or part-time Employment, I am a consultant for this biotech: Tessa Therapeutics Ltd; Financial Interests, Personal, Stocks/Shares: Tessa Therapeutics Ltd; Financial Interests, Institutional, Stocks/Shares, I am on the SAB and have stock options: Biosceptre Ltd; Financial Interests, Institutional, Invited Speaker, I am PI of an investigator initiated trial supported by: MSD Merck; Financial Interests, Personal and Institutional, Invited Speaker, I am coordinating PI for an investigator initiated trial supported by: BMS. E. Sirachainan: Financial Interests, Personal, Advisory Board: Merck, Roche, Taiho, MSD, Novartis. G.F. Ho: Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Advisory Board: MSD, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer; Financial Interests, Personal and Institutional, Full or part-time Employment: University Malaya Medical Centre, UM Specialist Centre; Financial Interests, Institutional, Research Grant: Eli Lily, Regeneron, MSD, AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca; Financial Interests, Institutional, Principal Investigator: Eli Lilly, Regeneron, MSD, AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Role: MSD, Novartis, Roche, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD, Novartis, Roche, Boehringer Ingelheim, AstraZeneca. C. Tan: Financial Interests, Personal, Full or part-time Employment: Tessa Therapeutics Ltd. C. Ding: Financial Interests, Personal, Full or part-time Employment: Tessa Therapeutics, Pte. Ltd.; Financial Interests, Personal, Stocks/Shares: Tessa Therapeutics, Pte. Ltd.; Non-Financial Interests, Project Lead: Tessa Therapeutics, Pte. Ltd. A. Myo: Financial Interests, Personal, Full or part-time Employment: Tessa Therapeutics Ltd. All other authors have declared no conflicts of interest.