Cancer vaccines enjoyed a moment in the spotlight this week as Moderna, Merck, Nykode Therapeutics and Transgene shared promising updates at AACR and beyond.
Pictured: Vaccine bottles lined up/courtesy of Mdisk/Adobe Stock
The burgeoning field of cancer vaccines enjoyed a moment in the spotlight this week as Moderna, Merck, Transgene and Nykode all reported promising updates.
While Moderna and Merck’s Phase II mRNA-4157/V940/Keytruda data, presented at the American Association for Cancer Research’s annual meeting, received the most attention, Oslo-based Nykode also revealed positive Phase II results for its therapeutic vaccine, VB10.16, in cervical cancer.
Nykode’s Vaccine Increases Survival in Advanced Cervical Cancer
In a Phase II trial, VB10.16 was used in combination with Roche’s PD-L1 inhibitor Tecentriq (atezolizumab) in patients with advanced or recurrent, non-resectable cervical cancer caused by the HPV16 virus. Fifty-two patients—48% of whose tumors were PD-L1-positive—were treated for up to one year and tracked for an additional year.
Median overall survival (mOS) in the entire population was 16.9 months, with a mOS in the PD-L1-positive cohort of greater than 25 months, the median having not yet been reached.
Nykode’s study compared results to Merck’s Keytruda and Regeneron’s Libtayo as monotherapies in advanced cervical cancer, where PD-L1+ patients have a mOS of 11 months and 13.9 months, respectively. Tecentriq as a monotherapy was not used for comparison as Roche has only run a small trial in cervical cancer, but Nykode Co-founder Agnete Fredriksen told BioSpace the data is expected to be similar.
The vaccine’s targeting unit is a unique component of its design, Fredriksen said, who invented the technology. The plasmid DNA-based vaccine includes an inflammatory chemokine linked to the antigen to ensure the antigen-presenting cells (APCs) traffic to the injection site.
Fredriksen compared this to other vaccine technology that goes into the bloodstream, “hoping it meets an antigen-presenting cell.”
Once the APC has processed the antigen, it presents for recognition to the T cells to initiate the adaptive immune response. Fredriksen said the concentration of the chemokine in Nykode’s design more effectively activates CD8 T cells. These killer T cells will seek out cancer cells presenting those antigens to kill them.
Nykode is planning another advanced cervical cancer trial combining VB10.16 with a to-be-determined immune checkpoint inhibitor. The potentially registrational trial should start before the end of the year.
“We hope and believe that this trial could serve as a basis for approval with the FDA,” Michael Engsig, CEO, told BioSpace in the same interview.
If everything goes well, Engsig hopes for FDA approval by 2028. With its strong safety profile and durable response, Fredricksen said Nykode will likely also pursue an early-stage indication to help prevent recurrence in patients who have just undergone tumor resection.
The program will also expand into head and neck cancer, which is also driven by the HPV16 virus.
At AACR, Nykode presented data from a Phase I/II trial of VB10.NEO, on which it is collaborating with Genentech. More than ten advanced setting indications are currently being explored in a basket trial. If successful, Fredriksen said the vaccine, in theory, could work in all cancer patients.
As of May 2022, 41 patients had received at least one injection of the personalized vaccine. Nykode reported that VB10.NEO was safe and well-tolerated, with all patients displaying immune responses to at least three neoepitopes.
Transgene Looks to Phase II in Head and Neck Cancer
Transgene presented preliminary data from its personalized neoantigen vaccine at AACR. The French biopharma is testing TG4050 in an ongoing Phase I trial for patients with HPV-negative head and neck cancer while enrolling patients with ovarian cancer in a parallel trial.
In head and neck cancer, an individualized vaccine is created for each patient after surgery. It is being tested as a monotherapy, given immediately after adjuvant therapy in half of the patients and at the time of disease recurrence in the rest.
All 16 patients who received TG4050 after resection have remained disease-free, with a median follow-up of 9.2 months, while two patients in the control arm experienced a relapse. Transgene expects the last patients to be treated in the coming weeks with final results expected in mid-2024.
A Phase II trial is planned for the second half of 2024 to include larger numbers of patients with site expansions across multiple countries, and discussions with regulatory agencies in both Europe and the U.S. are forthcoming, Kaïdre Bendjama, program director for personalized cancer vaccines at Transgene, told BioSpace.
Transgene’s vaccine is a viral vector, a design first introduced in the 1970s. Utilizing AI provided by its Japanese partner NEC, up to 30 DNA sequences of the tumor mutation are cloned and placed on the viral vector, which targets the most relevant cancer-specific neoantigens.
“There is a debate on the ability of [messenger RNA] to mount a long-lasting T cell memory response,” Eric Quéméneur, Transgene’s chief scientific officer, told BioSpace, noting the proven long memory response of the viral vector-based vaccines.
Moderna and Merck’s Therapeutic Vaccine Impresses in Advanced Melanoma
Moderna and Merck presented data from a Phase II trial comparing the safety and efficacy of their personalized cancer vaccine, mRNA-4157/V940, in combination with Merck’s Keytruda versus Keytruda alone in high-risk melanoma following complete resection. The vaccine led to a 44% reduction in recurrence or death.
While the data drew attention, concerns over the regulatory trajectory for the vaccine caused a stock drop of over 8% on Monday.
Jared Holz, an analyst at Mizuho told BioSpace in an email that it is still not clear what the true durability of mRNA-4157/V940 is and if further vaccination will be needed down the road.
A Phase III study in patients with adjuvant melanoma is slated to start later this year with hopes to expand into other tumor types, such as non-small cell lung cancer, according to Moderna and Merck.
Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
Correction (April 21): This story has been updated from its original version to clarify that Nykode’s Phase II results were not released at AACR. BioSpace regrets the error.
