Express Advanced colorectal cancer overall survival is extended by 3 times! Results of mRNA vaccines that effectively treat "cold" tumors are out

Gritstone bio recently announced the latest data
from its Phase 1/2 clinical trial of its individualized cancer vaccine GRANITE combined with immune checkpoint inhibitors as first-line maintenance therapy for the treatment of patients with advanced solid tumors 。 The analysis showed that in the population of patients with metastatic microsatellite stabilized colorectal cancer (MSS-CRC) who had received at least 2 lines of therapy, this combination therapy helped patients achieve molecular remission with a median overall survival (OS) of more than 22 months, which was 3 times that of patients who had received 3 lines of MSS-CRC in the past (median OS was only 6-7 months)! The detailed data will be announced at the 37th Annual Meeting of the Society for Cancer Immunotherapy (SITC) in 2022
.
Gritstone's Phase 2/3 clinical trial as a first-line maintenance therapy for patients with newly diagnosed MSS-CRC began in January this year and preliminary data
is expected in Q4 2023.

Colorectal cancer is one of
the most common and most serious cancers.
In 2020, more than 1.
9 million people worldwide were diagnosed with colorectal cancer and 935,000 people died
.
It is estimated that about one in ten cancer patients will die
from colorectal cancer among all cancer patients.
MSS-CRC patients accounted for 80-85% of patients with rectal cancer, whose tumors were considered "cold" and did not usually respond
to immunotherapy.

GRANITE is an mRNA vaccine
based on tumor neoantigens.
The cancer vaccine is designed to first obtain biopsy tissue from a patient, sequence the tumor, and then screen out tumor-specific neoantigens
using the proprietary artificial intelligence platform EDGE.
This cancer vaccine requires two inoculations, the first using adenovirus vectors to deliver neoantigen-expressing genes, and the second using self-amplifying mRNA vectors to deliver neoantigen-expressing mRNA, which in turn triggers a significant T cell response, especially CD8+ cytotoxic T cells
.
GRANITE has received fast-track designation from the U.
S.
FDA for the treatment of patients
with MSS-CRC.

Image source: 123RF

The main purpose of the Phase 1/2 trial announced this time is to review the safety, immunogenicity and clinical efficacy of GRANITE and nivolumab, a PD-1 immune checkpoint inhibitor, and ipilimumab, a CTLA-4 antibody for the treatment of advanced solid tumor patients, and a total of 29 solid tumor patients who have received early treatment were enrolled
。 Of the 13 MSS-CRC patients enrolled, 6 achieved a molecular response, meaning that the circulating tumor DNA (ctDNA) content in the patient decreased by ≥30% and continued to have OS advantage compared with those who did not achieve a molecular response.

The median OS of MSS-CRC patients who did not achieve a molecular response was 7.
8 months, while the median overall survival of 6 MSS-CRC patients who achieved a molecular response had not been reached, but it was more than 22 months
.
It should be noted that all MSS-CRC patients had <1% PD-L1 expression and low expression of interferon γ (IFNγ)-related
genes.
In addition, the number of tumor mutations in the 6 patients who developed molecular response was lower than that of patients who did not produce remission, and 4 of the tumors had liver metastases
in the past.

Image source: 123RF

Past interim analysis results from GRANITE's Phase 1/2 trial of advanced metastatic solid tumors were published in the august issue of Nature Medicine
.
The results show that GRANITE is able to generate robust, durable and functional tumor-specific CD4+ and CD8+ T cell responses that have potential broad applicability in a range of disease settings
.

"Data from our Phase 1/2 trial in MSS-CRC patients who have received at least 2 lines of therapy show that molecular response correlates with overall patient survival," said Andrew Allen, Ph.
D.
, co-founder, president and CEO of Gritstone.

In addition, we have seen molecular remission
in patients with metastatic tumors that were previously considered difficult to benefit from immunotherapy.
”

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