SAN DIEGO – Transgene and NEC this week said they would advance a trial testing the activity of their personalized neoantigen cancer vaccine in head and neck cancer into Phase II expansion cohorts.
The partners' decision is bolstered by a Phase I readout at the American Association for Cancer Research's annual meeting, which showed that all patients who got the personalized vaccine, TG4050, as an adjuvant therapy were still in remission, even a year-and-a-half later in some cases.
The cancer vaccine uses a non-pathologic viral vector to deliver up to 30 neoantigens specific to each patient's tumor and activate immune cells against it. Researchers used NEC's artificial intelligence and machine learning platforms to select the 30 neoantigens for each patient.
The non-pathologic viral vector delivery method is distinct from other personalized cancer vaccines in development that use messenger RNA. The viral vectors "have excellent safety profiles and have been used in hundreds of patients," Olivier Lantz, an immunologist and researcher at the Institut Curie in Paris, and an investigator on the TG4050 study, said during an AACR press conference on Tuesday. "They have proven immunogenicity and a large cargo capacity."
In the Phase I clinical trial, advanced, human papillomavirus (HPV)-negative head and neck squamous cell carcinoma patients underwent surgery to remove their tumors, Lantz said. Then, after receiving adjuvant chemotherapy, they were randomized to one of two treatment arms: one in which patients received repeated injections of the personalized vaccine as an additional adjuvant therapy and another in which they did not receive any additional adjuvant therapy, although the personalized vaccine was manufactured for all patients. If, and when, their cancers recurred, patients in both arms went on to receive TG4050 plus standard-of-care therapy, which could include immune checkpoint inhibitors.
Manufacturing the personalized neoantigen vaccine isn't quick. Lantz said that sequencing the tumors post-resection and identifying the 30 neoantigens takes about two weeks, after which it can take up to three months to actually make the vaccine. But this length of time is "compatible with an adjuvant setting," he said, because these patients have no detectable disease after surgery and are receiving adjuvant chemotherapy before they get the vaccine.
Of 32 patients randomized in the Phase I trial, all 16 patients who received the vaccine were still in remission at a median follow-up of 16.2 months, Lantz reported. In a statement on Tuesday, Transgene said these patients remain in remission after a median follow-up of 18.6 months.
In the control arm, three patients have experienced disease relapse. Roughly 40 percent of head and neck cancer patients are expected to experience cancer recurrence within two years of surgery and adjuvant therapy, according to Transgene.
Lantz added that head and neck cancer patients in the Phase I trial had low tumor mutational burden, which would usually make it challenging to identify neoantigens and design a vaccine against them. The fact the researchers were still able to home in on effective immunogenic targets in patients with low TMB shows the promise of Transgene and NEC's development approach for TG405, he said.
In terms of patients' immune responses to the vaccine, Lantz noted that 80 percent of the immunoreactivities detected after the vaccine were not seen at baseline, indicating that the vaccine caused these patients to generate tumor-specific T cells they didn't have before. In patients who received the vaccine, T cells continued to go after cancer cells for 211 days following the start of treatment. Among 17 patients who ultimately received the vaccine — 16 patients who were randomized to the TG4050 arm and one patient in the control arm who received the vaccine after relapse — investigators detected CD8-positive and CD4-positive T cells in 16 of them, indicating cellular immune responses.
"The clinical outcome is quite promising because you have no relapse in these high-risk patients receiving the vaccine post-primary treatment, versus three relapses in patients not receiving the vaccine," Lantz said.
Based on the Phase I data, Transgene and NEC are moving the trial into its Phase II portion in which they will enroll at least 23 head and neck cancer patients in each arm, said Lantz. "With that number of patients, we will have the power to detect a clinical benefit," he said. If this is successful, Lantz said Transgene and NEC would take their vaccine into Phase III trials.
In the meantime, Transgene Chairman and CEO Alessandro Riva called the Phase I data readout a "robust proof of principle" for the bespoke vaccine. "TG4050 is now starting to show a potential benefit for head and neck cancer patients at high risk of relapse," he said in a statement. "We look forward to starting the Phase II part of the trial in the adjuvant setting for head and neck cancer."
Transgene and NEC are planning to begin the Phase II expansion portion during the second quarter of this year.
The firms' latest findings on TG4050 adds to a growing body of promising clinical data on personalized cancer vaccines released at this year's AACR meeting. On Sunday, for instance, BioNTech and Roche released follow-up data showing that pancreatic cancer patients who initially responded to their mRNA-based neoantigen cancer vaccine lived longer without cancer progression than those who didn't respond initially.