The biotech’s personalized neoantigen vaccine for colorectal cancer did not demonstrate a molecular response difference from the control arm. Gritstone blames trial protocol and plans for a Phase III study.
Despite mixed mid-stage data, Gritstone bio is determined to head to Phase III with its personalized cancer vaccine. The biotech’s stock took a 32% pre-trading plummet Tuesday morning after the preliminary data drop was immediately followed by a public offering announcement.
GRANITE is Gritstone’s first oncology program. It’s being tested in patients with newly diagnosed, metastatic microsatellite-stable colorectal cancer (MSS-CRC) following a chemotherapy regimen with bevacizumab.
Patients in the open-label Phase II/III trial showed an early trend toward benefit for GRANITE. However, a short-term circulating tumor DNA (ctDNA) response analysis did not demonstrate a difference in the 39 patients treated versus the 28 in the control arm. Patients on the GRANITE vaccine regimen showed a molecular response of 30%, while the control arm came in at 41.7%. Gritstone pointed to the unanticipated continuation of the drop in ctDNA from induction chemotherapy in both arms, which generated similar short-term response rates.
“We simply got it wrong,” Gritstone CEO Andrew Allen said in a statement, acknowledging the inherent risk of “pioneering new spaces.”
Gritstone contends that a long-term analysis of more mature progression-free survival data in the third quarter will still lead to a Phase III regulatory discussion. Median PFS in high-risk patients was 12 months on GRANITE versus seven months in the control arm.
The population targeted by Gritstone’s most advanced program is a tough one. Metastatic colorectal cancer is the second most common cause of cancer death with up to 97% of patients categorized as metastatic microsatellite stable. These types of patients do not often benefit from checkpoint inhibitors, the company said, adding that their personalized neoantigen-directed vaccine could potentially drive efficacy in a metastatic “cold” tumor.
A cold tumor is surrounded by cells that suppress immune response to prevent T cells from attacking. J. Randolph Hecht, an investigator in the Phase II/III study, said GRANITE has the potential for benefit in not only MSS-CRC but other cold tumors as well.
The trial announcement celebrated the early trend in benefit for PFS and extended PFS benefit in high-risk patients. The biotech also pointed out it was able to manufacture a vaccine for each of the 39 patients in the treatment arm with a 100% success rate.
At the close of 2023, Gritstone projected its cash runway wouldn’t take the company through 2024. After posting the Phase II/III data on Monday, Gritstone announced a public offering of $32.5 million.
In February 2023, the biotech cut 40% of its workforce following a delay of its Phase IIb study for a self-amplifying mRNA COVID-19 vaccine, which cost the company funding from the U.S. Biomedical Advanced Research and Development Authority.
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.
