Interim Phase II data from Gritstone bio’s study evaluating GRANITE in September 2024 are described as “encouraging” in a company statement. The study evaluates Gritstone’s individualised neoantigen targeting immunotherapy in frontline microsatellite stable colorectal cancer (MSS-CRC) as maintenance therapy in combination with immune checkpoint inhibitors and fluoropyrimidine/bevacizumab. These data show the vaccine’s potential to extend progression-free and overall survival, but “fell short” of the target that some suggest is needed to “transform its fortunes”.
Encouraging data
104 patients were randomised 1:1 in the study, and the treated analysis shared by Gritstone includes 69 patients. Highlights from the data include:
- An emerging progression-free survival (PFS) benefit to all GRANITE recipients
- 21% relative risk reduction of progression or death with GRANITE compared to standard of care (SOC) control in all treated population
- 33% of GRANITE and 23% of control patients remain on study and free of progression
- Clinical benefit was most notable in patients with low disease burden (defined as patients with circulating tumour DNA (ctDNA) equal to or below the trial population median value at study entry)
- 38% relative risk reduction of progression or death with GRANITE compared to SOC control with low ctDNA subgroup
- Low baseline ctDNA is a likely prognostic and predictive factor
- Immune data were consistent with clinical activity
- Functional neoantigen-specific T cells observed in all 16/16 GRANITE patients tested by ELISPOT
- Association of PFS and peak ex vivo ELISPOT responses was apparent, indicating that ex vivo ELISPOT may be a surrogate for PFS
- GRANITE demonstrated a favourable safety and tolerability profile
- No patients discontinued study treatment due to an adverse event (AE)
- Common AEs were the mild systemic and local effects associated with any potent vaccine
- One treatment-related serious AE (fatigue) occurred in the GRANITE arm but patient continued GRANITE treatment without recurrence upon recovery
Gritstone recognises a need for continued follow-up to “fully assess” the effects of GRANITE and determine whether a plateau of improved PFS, which indicates durable clinical benefit, is achieved. Gritstone bio’s co-founder, President, and CEO Dr Andrew Allen is “excited by the potential” seen in GRANITE to extend both progression-free and overall survival “in a disease where relentless progression is the rule with existing therapies”.
“The field of neoantigen-targeting immunotherapy is evolving rapidly, and the focus is shifting to patients with lower volume disease. Notably, patients with newly diagnosed metastatic disease who have lower ctDNA at study entry and thereby relatively low disease burden, could benefit from this type of immunotherapy.”
More time needed
Dr Allen commented that “typically”, success for immunotherapy “manifests as an elevated plateau in PFS and overall survival Kaplan-Meier curves, and we may be seeing this in our low disease burden population.”
“We need more time to let these data mature.”
The “low and stable” ctDNA measurements in “most” GRANITE patients are “encouraging”, says Dr Allen, as that pattern is “not typically seen in patients about to develop disease progression”. There is also “opportunity for greater effects in tumours more typically amenable to immunotherapy” in the potential benefit observed in MSS-CRC, a “notoriously ‘cold’ tumour”.
“These data support further exploration of GRANITE in frontline MSS-CRC and in other low burden (neo)adjuvant settings. With this new dataset in hand, we continue to actively explore several strategic and funding alternatives to rapidly advance our innovative immunotherapy for the benefit of patients.”
Head above water
The company statement also confirmed that Gritstone has engaged a financial advisor to support its exploration and review of potential “value-maximising strategies”. While Gritstone “does not intend to discuss or disclose further developments”, speculation continues.
Evercore ISI analyst Jonathan Miller is quoted by Fierce Biotech wondering if the company’s cash runway is “functionally no later than” the end of the year. Although “on the face of it” the progress is positive, the data have “limitations”, such as a shift away from patients with more aggressive disease. Miller believes that if Gritstone can keep tracking patients, the extend follow up can continue to look encouraging, but questions the company’s future.
“They don’t have flexibility to run this data out much further, add [patients], or explore [the] adjuvant setting.”
We look forward to welcoming Gritstone’s EVP and Head of R&D, Dr Karin Jooss, to the Congress in Barcelona this month, to share insights in the Cancer and Therapeutic Vaccines track. Get your tickets to join us here, and don’t forget to subscribe to our weekly newsletters for the latest vaccine news.
