First Evidence of Efficacy of mRNA Cancer Treatment
According to the results of the phase IIb KEYNOTE-942 trial, the combination of mRNA-4157/V940 and pembrolizumab significantly reduces the risk of disease recurrence or death in stage III/IV melanoma patients with a high risk of recurrence following complete resection compared to pembrolizumab monotherapy.[1] These findings represent the first evidence of the efficacy of an investigational mRNA cancer treatment in a randomised clinical trial.[1]
On December 13th, 2022, Moderna and Merck presented the primary efficacy endpoint results from the ongoing phase IIb KEYNOTE-942 trial, which is evaluating the mRNA-4157/V940, an investigational personalised mRNA cancer vaccine, in combination with pembrolizumab, Merck’s anti-PD-1 therapy, in stage III/IV melanoma patients.[1].
What essentially is mRNA-4157/V940 and why is it combined with pembrolizumab?
The mRNA-4157/V940 is a novel investigational messenger ribonucleic acid (mRNA)-based personalised cancer vaccine that is intended to stimulate an immune response by generating specific T cell responses based on a patient’s tumour’s unique mutational signature.[1],[2]
Considering that pembrolizumab is an anti-programmed death receptor-1 (PD-1) that boosts the immune system’s ability to detect and fight tumour cells, combining it with mRNA-4157/V940 may potentially provide an additive benefit, improving T cell-mediated tumour cell destruction.[1],[2]
Why is this approach novel and promising?
Cancer is challenging to treat because cancer cells have unique cancer “fingerprint” proteins, making each patient’s cancer case different. Given the fact that the personalised mRNA cancer vaccine is designed by matching each patient’s cancer “fingerprint,” it appears to be an innovative and promising approach.[2]
The KEYNOTE-942 phase IIb trial methodology
The KEYNOTE-942 is an ongoing randomised, open-label phase IIb trial aimed to determine whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence-free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence.[1],[3]
Following complete surgical resection, 157 patients with stage III/IV melanoma were randomly assigned to receive up to 9 doses of mRNA-4157/V940 (every 21 days) plus pembrolizumab (200 mg every 3 weeks for up to 18 cycles) or pembrolizumab alone for approximately one year until disease recurrence or unacceptable toxicity.[1],[3]
Primary efficacy endpoint findings from the phase IIb KEYNOTE-942 trial
The phase IIb KEYNOTE-942 trial demonstrated that the combination of mRNA-4157/V940 and pembrolizumab improves the RFS compared to the pembrolizumab alone in patients with stage III/IV melanoma following complete resection. Adjuvant treatment with mRNA-4157/V940 plus pembrolizumab reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p value=0.0266) compared with the pembrolizumab monotherapy.[1],[3]
The mRNA-4157/V940 and pembrolizumab safety profiles were consistent with those observed in previous studies. Serious treatment-related adverse events occurred in 14.4% of patients given the combination of mRNA-4157/V940 and pembrolizumab, compared to 10% of patients given pembrolizumab alone.[1],[3]
What do these findings mean for upcoming cancer studies and treatments?
Moderna and Merk see these findings as extremely promising for cancer treatment, and they intend to launch a phase III study for melanoma in 2023, and rapidly expand trials to other tumour types.[1]
“With data expected this quarter on personalised cancer vaccines, we continue to be excited about the future and the impact mRNA can have as a new treatment paradigm in the management of cancer”, said Moderna President Stephen Hoge, M.D. “Continuing our strategic alliance with Merck is an important milestone as we continue to grow our mRNA platform with promising clinical programs in multiple therapeutic areas.“
REFERENCE:
- https://www.targetedonc.com/view/personalized-mrna-cancer-vaccine-reduces-rate-of-recurrence-in-melanoma (access: 09.01.2023.)
- https://www.modernatx.com/media-center/all-media/blogs/fight-against-cancer (access: 09.01.2023.)
- https://clinicaltrials.gov/ct2/show/NCT03897881 (access: 09.01.2023.)