GRANITE Plus ICIs and Bevacizumab/Chemo Shows Improved PFS Trend in MSS mCRC

Maintenance therapy consisting of the individualized neoantigen targeting GRANITE (GRT-C901/GRT-R902), atezolizumab (Tecentiq), ipilimumab (Yervoy), bevacizumab (Avastin), and fluoropyrimidine continued to show a trend of improved progression-free survival (PFS) compared with bevacizumab plus fluoropyrimidine alone in patients with first-line microsatellite stable (MSS) metastatic colorectal cancer (mCRC), according to updated data from the phase 2 GO-010 trial (NCT05141721).¹

Findings showed that in the overall population (n = 69), the GRANITE-based regimen reduced the risk of death by 27% vs the control regimen at the October 2024 data cutoff (HR, 0.73; 90% CI, 0.44-1.21). At data cutoff, 28% of patients in the GRANITE arm (n = 39) remained progression-free compared with 13% of patients in the control arm (n = 30). Notably, an increased PFS benefit was seen in the subgroup of patients with low levels of circulating tumor DNA (ctDNA; n = 31; HR, 0.50; 90% CI, 0.20-1.28) vs those with high levels of ctDNA (n = 30; HR, 0.78; 90% CI, 0.39-1.58).

“Our encouraging phase 2 data for GRANITE in MSS CRC continue to mature and demonstrate durable benefit over time. With 2 additional months of follow-up, relative PFS has further improved in the analysis of all patients treated with GRANITE, and most notably, in those with a lower tumor burden at study baseline,” Andrew Allen, MD, PhD, co-founder, president, and chief executive officer of Gritstone bio, stated in a news release. “The powerful antitumor immunity induced by GRANITE in an immunologically cold tumor setting like MSS CRC underscores a differentiated approach with a multitude of expansion opportunities across solid tumor indications. Moreover, these data also further de-risk SLATE, our off-the-shelf cancer immunotherapy program, and more importantly, reinforce the transformative potential of Gritstone’s overall immunotherapy platform.”

GO-101 was an open-label, randomized study that enrolled patients at least 18 years of age with histologically confirmed metastatic CRC who planned to receive or had received less than 30 days of first-line treatment in the metastatic setting with a standard-of-care (SOC) chemotherapy regimen in combination with bevacizumab.² Key inclusion criteria consisted of measurable and unresectable metastatic disease per RECIST 1.1 criteria; availability of formalin-fixed paraffin-embedded tumor specimens; an ECOG performance status of 0 or 1; and adequate organ function.

Patients were excluded if they had mismatch repair–deficient or microsatellite instability–high disease; had a known tumor mutation burden of less than 1; harbored known DNA polymerase epsilon mutations; or had known BRAF V600E mutations.

After receiving 24 weeks of induction therapy with SOC chemotherapy plus bevacizumab, patients were randomly assigned to 1 of 2 arms. In the experimental arm, patients received 6 total administrations of GRANITE, along with 1 dose of ipilimumab at 30 mg administered with the first dose of GRANITE, followed by atezolizumab at 1680 mg once every 4 weeks plus standard maintenance with a fluoropyrimidine and bevacizumab. In the control arm, patients received a fluoropyrimidine and bevacizumab alone.

The primary end point in phase 2 was the rate of molecular responses, defined as at least a 30% decrease from baseline in ctDNA. Secondary end points included safety, PFS, overall survival (OS), overall response rate, duration of response, clinical benefit rate, and deepening of response.

OS data remained immature and are expected to read out in the second half of 2025.¹ Safety data showed GRANITE was tolerable.

“We are focused on our mission to deliver potentially life-saving treatments like GRANITE to millions of patients worldwide and continue to explore several strategic and funding alternatives during the financial restructuring process,” Allen added in the news release. “The compelling PDS data in a challenging disease context, coupled with a well-tolerated safety profile, supports further continuation of the GRANITE program by a party who shares our vision to deliver novel treatments leveraging the immune response to fight tough-to-treat cancers.”

References

1. Gritstone bio announces strengthening of maturing phase 2 PFS data for GRANITE study and provides business update. News release. Gritstone bio. November 11, 2024. Accessed November 14, 2024. https://ir.gritstonebio.com/news-releases/news-release-details/gritstone-bio-announces-strengthening-maturing-phase-2-pfs-data
2. A study of a patient-specific neoantigen vaccine in combination with immune checkpoint blockade for patients with metastatic colorectal cancer. ClinicalTrials.gov. Updated December 22, 2023. Accessed November 14, 2024. https://clinicaltrials.gov/study/NCT05141721