Combination CAR T-Cell Therapy, RNA Vaccine Shows Efficacy in Solid Tumors
The novel regimen from BioNTech demonstrated encouraging results in patients with testicular or ovarian cancer.
A novel combination approach that includes an autologous CAR T-cell therapy and a CAR T-cell amplifying RNA vaccine has shown preliminary efficacy in patients with advanced solid tumors. Data on BNT211 from the ongoing phase 1 /2a trial were presented at the 2022 American Association for Cancer Research Annual Meeting, April 8-13, 2022, in New Orleans, Louisiana.1
The combination regimen from COVID-19 vaccine player BioNTech utilizes a CAR T-cell product that targets tumor specific antigen claudin 6 (CLDN6)-positive solid tumors and a CAR T-cell amplifying RNA vaccine, CARVac, that helps improve CAR T-cell therapy persistence and functionality. The combination is currently being explored in an ongoing 2 part, phase 1/2a dose escalation trial (NCT04503278) in heavily pretreated patients with a median of 4 to 5 prior lines of treatment with CLDN6-positive relapsed or refractory advanced solid tumors, with a target enrollment of 36 participants.
As of the data cutoff, 16 patients were treated in the dose level 1 (1x107 CAR-T cells) and 2 (1x108 CAR-T cells) groups alone (n=9) or combined with CARVac (n=7), which is administered every 3 weeks for 5 treatments, followed by a maintenance dose administered every 6 weeks. Generally well tolerated, investigators observed 37 ≥ Grade 3 adverse events (AEs) related to the drug product, including cytopenia and asymptomatic transaminase and lipase elevations. Two dose-limiting toxicities were reported: grade 4 cytopenia in part 1 of dose level 2 and grade 4 hemophagocytic lymphohistiocytosis at part 2 of dose level 2. Notably, based on the observance of prolonged cytopenia in patients with testicular cancer with a history of high-dose chemotherapy and stem cell transplant, a reduced lymphodepletion cohort has been launched. Low-grade cytokine release syndrome was observed in 8 patients without any signs of neurotoxicity.
Peripheral blood analysis revealed robust CAR T-cell engraftment of near 109 total counts, peaking around day 17. Six weeks post-infusion, 6 of the 14 evaluable participants showed a partial response (4 with testicular cancer and 2 with ovarian cancer) with a 39% to 49% shrinkage of target lesions, and 5 had stable disease with evidence of shrinkage of target lesions, with an overall response rate of 43% and a disease control rate of 86%. Notably, 1 patient showed no change and 2 were progressing. At 12-week follow-up, 4 of the 6 patients with PR showed a deepening and durability of response (50%-73% shrinkage), and 1 patient reached complete response at 18 weeks (dominant EMRA phenotype of transferred CAR T-cells and persistence of more than 150 days post-infusion).
Patients with testicular cancer in the dose-level 2 group (n=4) had disease control, and 3 had objective responses. One testicular cancer patient in part 2 of the dose-level 1 group who received the reduced lymphodepletion did show a partial response. Overall, more robust antitumor activity was observed in the higher dose level group when combined with CARVac, with 4 of 5 patients showing a partial response.
“Claudin-6 was never targeted with cellular therapy before, but in this study, the approach is already showing an efficacy that may be better than the data from other CAR-T trials in solid tumors,” said John Haanen, MD, PhD, principal investigator and medical oncologist at the Netherlands Cancer Institute in Amsterdam, Netherlands.2 “While the data are very early, it is remarkable that all patients with testicular cancer showed clinical benefits at dose level 2, and the responses we have observed can be deep, including one ongoing complete remission. I look forward to further evaluating this exciting new modality for solid tumor patients.”
BioNTech expects to read out additional data from the ongoing trial in the second half of this year.
REFERENCES
1. Haanen JB, Mackensen A, Koenecke C, et al. BNT211: A Phase I trial to evaluate safety and efficacy of CLDN6 CAR-T cells and CARVac-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumors. Presented at: 2022 American Association for Cancer Research Annual Meeting. April 8-13, 2022; New Orleans, Louisiana. Abstract CT002.
2. BioNTech Presents Positive Preliminary Phase 1/2 Data for First-in-Class CAR-T Program BNT211 at AACR. News release. BioNTech. April 11, 2022. https://investors.biontech.de/news-releases/news-release-details/biontech-presents-positive-preliminary-phase-12-data-first-class
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