Item 8.01 Other Events.
On April 1, 2024, Gritstone bio, Inc. (the “Company”) announced preliminary progression-free survival (“PFS”), long-term circulating tumor DNA (“ctDNA”) and tolerability data from the Phase 2 portion of its randomized, open-label Phase 2/3 study evaluating its personalized cancer vaccine, GRANITE (GRTC901/GRT-R902), in combination with immune checkpoint blockade for patients with front-line metastatic microsatellite stable colorectal cancer. Of the 104 patients randomized, 67 (39 GRANITE arm, 28 control arm) were included in the preliminary dataset, with cutoff dates of March 8, 2024 and March 12, 2024, as indicated below. Thirty-six patients left the study prior to randomized treatment primarily due to early progressive disease or withdrawal of consent, and one patient has yet to begin study treatment start. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with approximately 75% of patients having liver metastases.
Progression-free survival data
Preliminary PFS data showed an overall trend of clinically meaningful improvement in GRANITE recipients, with hazard ratios of 0.82 in all patients ([95% CI, 0.34, 1.67]; 62% censored) and 0.52 (equating to a 48% relative risk reduction of progression or death with GRANITE vs. control) in a high-risk group ([95% CI, 0.15-1.38]; 44% censored); the high risk group defined as baseline ctDNA above the median value (2%) for the control group (ctDNA quantified as mean variant allele frequency (VAF) at the time of study randomization). As of the March 8, 2024 data cut, median PFS in the group of high-risk patients, who typically progress earlier than non-high-risk patients, was 12 months (GRANITE arm) and seven months (control arm). Greater than 90% of patients in the group of high-risk patients had liver metastases.
ctDNA data
As of the March 12, 2024 data cut, preliminary findings of short-term molecular response (>30% reduction in ctDNA using single time-point analysis, defined per protocol) appeared uninformative due to an unanticipated continuation of ctDNA drop beyond induction chemotherapy, and resulted in similar short-term molecular response rates across arms (GRANITE and control). Conversely, long-term ctDNA data demonstrated the expected correlation of ctDNA with clinical benefit and favored GRANITE patients. Multiple subgroup analyses spanning high and low-risk groups demonstrated alignment between ctDNA response and PFS trends.
Tolerability data
GRANITE was generally well tolerated. Common adverse events (“AEs”) were mild systemic and local effects typically associated with any potent vaccine, i.e., transient flu-like illness and the vast majority of AEs were Grade 1/2. As of the March 8, 2024 data cut, no patients had discontinued trial due to an AE.
The Company expects to provide mature PFS data in the third quarter of 2024 and overall survival data in the first half of 2025.
