Gritstone Advances to Phase III Despite Cancer Vaccine Trial Setback

Gritstone bio, a biotechnology firm, is moving forward with its personalized cancer vaccine, GRANITE, into Phase III clinical trials despite facing a 32% drop in its stock value after the release of mixed mid-stage results and a public offering announcement. GRANITE is designed for patients with metastatic microsatellite-stable colorectal cancer (MSS-CRC) and is being tested following chemotherapy combined with bevacizumab.

In the open-label Phase II/III trial, an early trend indicated potential benefits for GRANITE. However, a short-term analysis of circulating tumor DNA (ctDNA) response showed no significant difference between the 39 patients who received the vaccine and the 28 in the control group. The molecular response rate was 30% for the vaccine group, compared to 41.7% for the control group. Gritstone attributed the similarity to the unexpected ongoing reduction of ctDNA from induction chemotherapy in both groups.

The CEO of Gritstone, Andrew Allen, admitted the company's miscalculation, highlighting the risks of venturing into new medical frontiers. Despite the setback, Gritstone remains optimistic that a long-term analysis of progression-free survival (PFS) data, expected in the third quarter, will support a Phase III regulatory discussion. The median PFS for high-risk patients was noted to be 12 months with GRANITE, as opposed to seven months for the control group.

Gritstone's focus on metastatic colorectal cancer is challenging, given that it is the second most common cause of cancer-related deaths. Approximately 97% of these patients have metastatic microsatellite stable cancer, a group that typically does not benefit from checkpoint inhibitors. Gritstone believes its personalized vaccine could enhance the effectiveness against such "cold" tumors, which are surrounded by cells that inhibit the immune response, preventing T cells from attacking.

J. Randolph Hecht, a Phase II/III study investigator, suggested that GRANITE could potentially benefit other types of cold tumors as well. The trial announcement highlighted the early trend in PFS benefits and the extended PFS benefits for high-risk patients. Additionally, Gritstone successfully manufactured a vaccine for each patient in the treatment arm with a 100% success rate.

At the end of 2023, Gritstone anticipated that its cash reserves would not last beyond 2024. Following the release of the Phase II/III data, the company announced a public offering of $32.5 million. In February 2023, Gritstone had reduced its workforce by 40% after a delay in its Phase IIb study for a self-amplifying mRNA COVID-19 vaccine, which resulted in a loss of funding from the U.S. Biomedical Advanced Research and Development Authority.