BioNTech’s post-Comirnaty future is emerging, with early phase 1/2 data from a solid tumor CAR-T cell therapy showing evidence of efficacy and a safety profile deemed manageable by the famed German biotech.
With just 16 patients reporting, BioNTech said treatment with BNT211 was associated with a disease control rate of 86% and an overall response rate of 43%. The data was presented over the weekend at the American Association for Cancer Research meeting in New Orleans.
There's a lot to unpack in the results, so let’s start with the basics. BNT211 is an autologous CAR-T cell therapy that targets oncofetal antigen Claudin-6 that is being tested in the phase 1/2 solid tumor trial with or without a CLDN6-encoding CAR-T cell amplifying RNA vaccine called CARVac. The vaccine, which is based on BioNTech’s mRNA-lipoplex technology, is meant to boost CAR-T therapy and prolong the treatment effect at low doses.
The AACR results come from the first evaluable dose levels of BNT211.
BioNTech found robust CAR-T cell expansion 10 to 17 days after infusion in all 16 patients, who had testicular, ovarian, endometrial, fallopian tube or gastric cancer or sarcoma. Six weeks after infusion, six out of 14 evaluable patients showed a partial response, and five had stable disease and evidence of tumor shrinkage, BioNTech said. One patient showed no change at that time, while two were continuing to progress. Responses were seen in four patients with testicular cancer and two with ovarian cancer.
As of 12 weeks, four of the six patients who had achieved a partial response showed what BioNTech called a “deepening and durability” of response. One patient had a complete response after 18 weeks. All four patients with testicular cancer in the higher dose group of the trial had disease control, including three who had objective responses. One patient in this group who received the lowest infusion dose with CARVac had a partial response.
BioNTech concluded that a higher CAR-T dose combined with CARVac seemed to spur the most antitumor activity. Four out of five patients in the CARVac group had a partial response.
Safety data was limited, but BioNTech did report instances of grade 1 and 2 cytokine release syndrome and one occurrence of neurotoxicity grade 1. The “adverse events and dose-limiting toxicities were manageable,” the company said.
Cytokine release syndrome is a known complication of CAR-T therapy, which rapidly activates the immune system to fight cancer. The complication is graded from 1, meaning a mild reaction that requires supplementary care but does not have to interrupt treatment, to grade 4, which is a life-threatening complication that requires ventilation support and other immediate interventions. At grade 2, which means some signs of organ dysfunction are present, interruption of treatment is recommended.
BioNTech Co-Founder and Chief Medical Officer, Özlem Türeci, M.D., said the results seen with even the lowest doses in the heavily pretreated population were “truly remarkable,” and support the company’s hypothesis that Claudin-6 is a viable new tumor target.
“Bringing these innovations together in one regimen may benefit patients with hard-to-treat solid tumors with an otherwise poor prognosis, such as advanced testicular cancer,” Türeci said. “Our preliminary data indicate that the successes of CAR-T in hematological cancers may indeed be transferred to solid tumors.”
John Haanen, M.D., Ph.D., principal investigator of the study and a medical oncologist at the Netherlands Cancer Institute, was particularly impressed by the data in testicular cancer patients.
“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,” Haanen said.
The phase 1/2 trial continues, with a goal of evaluating the safety and early efficacy of BNT211.