The phase 2/3 GRANITE-CRC-1L clinical trial has been initiated.
The individualized neoantigen vaccine GRANITE, in combination with nivolumab (Opdivo) and ipilimumab (Yervoy), has been dosed in a patient with newly diagnosed, metastatic, microsatellite-stable colorectal cancer (MSS-CRC), initiating the phase 2/3 GRANITE-CRC-1L trial, according to a press release by Gritstone bio, Inc.1
GRANITE-CRC-1L is a study that has registrational intent and is the result of prior conversations with the FDA. A fast track designation by the FDA was also granted to GRANITE for the treatment of MSS-CRC. The phase 2/3 trial follows a successful phase 1/2 trial of the agent in this patient population.
In 26 patients with MSS-CRC, treatment with GRANITE combined with nivolumab/ipilimumab achieved a 44% molecular response rate (MRR). This MRR was found to correlate with an extended median overall survival (OS) greater than 17 months.2
“Building on the success of our GRANITE program, which continues to demonstrate extended survival in multiple end-stage colorectal cancer patients, we are excited to launch this randomized, open-label phase 2/3 trial to evaluate earlier use of GRANITE as a maintenance treatment in newly diagnosed patients with metastatic, microsatellite-stable colorectal cancer,” said Andrew Allen, MD, PhD, co-founder, president, and chief executive officer of Gritstone, in a press release.1 “We are pleased with the degree of clinical benefit seen with GRANITE to date in hard-to-treat, late-line CRC patients, and are optimistic we will see greater benefit from neoantigen immunotherapy in earlier lines of treatment where immune responses are likely stronger and tumor genomic complexity is lower.”
In the randomized, open-label GRANITE-CRC-1L study, approximately 665 patients will be enrolled and randomized to either the vaccine arm or a control arm in which patients will receive fluoropyrimidine, oxaliplatin, and bevacizumab (Avastin) following up to 24 weeks of induction therapy.
The phase 2 portion of the study is investigating the primary end point of anti-tumor activity. The phase 3 primary end point will be progression-free survival (PFS). The secondary end points of the study include the incidence of adverse events, PFS per investigator assessment, PFS per blinded independent review committee, OS, overall response rate, duration of response, clinical benefit rate, deepening of response, and success of vaccine manufacture.3
To be eligible for the study, patients are required to have histologic confirmation of metastatic MSS-CRC, measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and adequate organ function. Those excluded from the study are patients with microsatellite instability-high disease, known DNA polymerase epsilon mutations, BRAF V600E mutations, bleeding disorders, and other comorbidities that may interfere with study treatment.
“We expect to report initial phase 2 data from the GRANITE-CRC-1L trial in mid-2023,” Allen said in the press release.
1. Gritstone announces first patient enrolled for phase 2/3 trial evaluating individualized neoantigen vaccine GRANITE for first line (1L) maintenance treatment of metastatic, microsatellite-stable colorectal cancer (MSS-CRC). News release. January 13, 2022. Accessed January 17, 2022.
2. Gritstone announces positive clinical data with GRANITE (Individualized Neoantigen Immunotherapy Program) during ESMO 2021 and launch of randomized clinical trial program in colorectal cancer with registrational intent. News release. September 17, 2021. Accessed January 17. 2022. https://bit.ly/3rkzDaK
3. A Study of a personalized neoantigen vaccine in combination with immune checkpoint blockade for patients with metastatic colorectal cancer. Clinicaltrials.gov. Accessed January 17, 2022. https://bit.ly/3fyWp9u