BioNTech made its debut breakthrough in mRNA-based vaccines after using the technology to solve COVID-19 in the shortest time in history for a pandemic outbreak.
Now, the Germany-based biotechnology Company is hunting for a vaccine solution for pancreatic cancer, one of the most stubborn and deadliest cancers in the world, giving patients hope of a chance at protection.
The initial data from phase one of its first human trial in a study evaluating the safety and tolerability of the mRNA-based individualized immunotherapy called autogene cevumeran, in combination with chemotherapy in patients with resected pancreatic ductal adenocarcinoma (PDAC) shows positive signs.
The study confirmed the feasibility of the process of profiling each patient’s tumour to inform individualized vaccine design and on-demand manufacturing of iNeST in a clinically relevant timeframe.
The preliminary results showed a favourable safety profile as well as encouraging signs of clinical activity, the company said in an official statement noting that the data have been presented at the American Society of Clinical Oncology (ASCO) annual meeting 2022.
Autogene cevumeran is the lead candidate from BioNTech’s iNeST platform, which is jointly developed together with Genentech, a member of the Roche Group, in multiple solid tumour indications.
The data presented include a total of 19 patients who underwent surgery and received atezolizumab. 16 out of these 19 patients (84 percent) received autogene cevumeran at 9.4 weeks after surgery. The preliminary data readout from these 16 vaccinated patients revealed that autogene cevumeran in combination with atezolizumab was well-tolerated.
Only one of 16 patients (6 percent) developed a vaccine-related Grade 3 fever and hypertension with no other higher adverse events were observed.
In addition, the treatment induced a neoantigen-specific T cell response in half of these patients from undetectable levels to large fractions of all blood T.
At an early median follow-up of 18 months, patients with immune response to first occurrence of cancer had a significantly longer recurrence-free survival as compared to those without vaccine-induced immune responses.
Based on these data, BioNTech and Genentech are planning a randomized study to further evaluate the efficacy and safety of autogene cevumeran in combination with atezolizumab and chemotherapy in patients with resected PDAC.
“With only under 5 percent of patients responding to current treatment options, PDAC is one of the highest unmet medical need cancers. We are committed to taking up this challenge by leveraging our long-standing research in cancer vaccinology and are trying to break new ground in the treatment of such hard-to-treat tumors,” said Özlem Türeci, co-founder and chief medical officer at BioNTech.
“The results of this phase one study are encouraging. We look forward to further evaluating these early results in a larger randomized study.”
According to the company, the primary objective of the study is to assess the safety while the secondary objectives include the efficacy of the treatment measured as well as the feasibility of the treatment regimen.
Vinod Balachandran, surgeon-scientist at Memorial Sloan Kettering Cancer Center and principal investigator of the study explained that pancreatic cancer remains one of the deadliest cancers due to its resistance to all treatments, including immunotherapies.
The conventional thinking, he said, has been that pancreatic cancers have few mutations, making the immune system unlikely to recognise mutation-derived neoantigens.
“Our research, and now the results from this study show that the immune system can recognize neoantigens in pancreatic cancer and that we can use mRNA vaccines to stimulate T cells to recognize neoantigens in pancreatic cancer patients. We now look forward to further investigating these results in a larger randomized trial,” he said.
PDAC is amongst the leading causes of cancer-related deaths and even though a combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes, the relapse rate remains high after surgery.
The five-year overall survival is only approximately 20 percent in patients who undergo surgery followed by adjuvant chemotherapy (ACT) and only 10 percent in those who do not receive ACT.
Consequently, there is a high unmet medical need for novel therapies for patients with resected PDAC.