Gritstone bio Announces Interim Phase 2 Data for GRANITE Individualized Neoantigen Targeting Immunotherapy in Frontline Metastatic Microsatellite Stable Colorectal Cancer
Gritstone bio announced encouraging interim Phase 2 data for GRANITE, its individualized neoantigen targeting immunotherapy, in frontline microsatellite stable colorectal cancer (MSS-CRC). The study showed a 21% relative risk reduction of progression or death with GRANITE vs. control in all treated population (HR=0.79). In the low ctDNA subgroup, there was a 38% relative risk reduction (HR=0.62). The strength of neoantigen-specific T cell responses in GRANITE patients appears to associate with progression-free survival. GRANITE was generally well-tolerated with no treatment discontinuations due to adverse events. Overall survival data is expected in 2H 2025.
The study included 104 randomized patients, with 69 in the treated analysis. GRANITE demonstrated a favorable safety profile, with common adverse events being mild systemic and local effects associated with potent vaccines. Gritstone plans to review the PFS data with FDA and discuss next steps, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.
Gritstone bio ha annunciato dati intermedi incoraggianti di Fase 2 per GRANITE, la sua immunoterapia mirata a neoantigeni individualizzati, nel trattamento iniziale del cancro colo-rettale microsatellite stabile (MSS-CRC). Lo studio ha mostrato una riduzione del rischio relativo del 21% di progressione o morte con GRANITE rispetto al gruppo di controllo nell'intera popolazione trattata (HR=0,79). Nel sottogruppo a bassa ctDNA, è stata riscontrata una riduzione del rischio relativo del 38% (HR=0,62). La forza delle risposte delle cellule T specifiche per neoantigeni nei pazienti trattati con GRANITE sembra essere associata alla sopravvivenza libera da progressione. GRANITE è stato generalmente ben tollerato, senza interruzioni del trattamento a causa di eventi avversi. I dati sulla sopravvivenza totale sono previsti per il secondo semestre del 2025.
Lo studio ha incluso 104 pazienti randomizzati, di cui 69 nell'analisi trattata. GRANITE ha dimostrato un profilo di sicurezza favorevole, con eventi avversi comuni che erano effetti sistemici e locali lievi associati a potenti vaccini. Gritstone prevede di esaminare i dati PFS con la FDA e discutere i prossimi passi, inclusa una potenziale sperimentazione di Fase 2 o 3 utilizzando i livelli di ctDNA come criterio di idoneità.
Gritstone bio anunció datos interinos alentadores de la Fase 2 para GRANITE, su inmunoterapia dirigida a neoantígenos individualizados, en el cáncer colorrectal estable microsatélite (MSS-CRC) en primera línea. El estudio mostró una reducción del riesgo relativo del 21% de progresión o muerte con GRANITE en comparación con el control en toda la población tratada (HR=0.79). En el subgrupo de baja ctDNA, hubo una reducción del riesgo relativo del 38% (HR=0.62). La fuerza de las respuestas de células T específicas para neoantígenos en los pacientes de GRANITE parece asociarse con la supervivencia libre de progresión. GRANITE se toleró generalmente bien, sin interrupciones del tratamiento debido a eventos adversos. Se esperan datos de supervivencia global en la segunda mitad de 2025.
El estudio incluyó a 104 pacientes aleatorizados, con 69 en el análisis tratado. GRANITE demostró un perfil de seguridad favorable, con eventos adversos comunes que eran efectos sistémicos y locales leves asociados con potentes vacunas. Gritstone planea revisar los datos de PFS con la FDA y discutir los próximos pasos, incluida una posible prueba de Fase 2 o 3 utilizando los niveles de ctDNA como criterios de elegibilidad.
그릿스톤 바이오는 GRANITE, 개인화된 신항원 표적 면역요법에 대한 임상 2상 중간 데이터를 발표했습니다. 이 연구는 최초의 미세위성 안정 대장암 (MSS-CRC) 치료에서 GRANITE와 대조군 간의 진행이나 사망 위험이 21% 감소했다고 보고했습니다 (HR=0.79). 저 ctDNA 하위 그룹38%의 상대위험 감소가 있었습니다 (HR=0.62). GRANITE 환자에서 신항원 특이 T 세포의 반응 강도는 진행 없는 생존( progression-free survival)과 연관이 있는 것으로 보입니다. GRANITE는 일반적으로 잘 견디며, 이상반응으로 인해 치료가 중단된 경우는 없었습니다. 전체 생존 데이터는 2025년 하반기에 발표될 예정입니다.
이 연구는 104명의 무작위 환자를 포함했으며, 치료 분석에는 69명이 포함되었습니다. GRANITE는 매우 안전한 프로필을 보여주었으며, 일반적인 부작용은 강력한 백신과 관련된 경미한 전신 및 국소 효과였습니다. 그릿스톤은 FDA와 PFS 데이터를 검토하고, ctDNA 수치를 자격 기준으로 사용하는 2상 또는 3상 시험의 다음 단계를 논의할 계획입니다.
Gritstone bio a annoncé des données intermédiaires encourageantes de la phase 2 pour GRANITE, sa thérapie immunitaire ciblant des néoantigènes individualisés, dans le cancer colorectal stable par microsatellite (MSS-CRC) en première ligne. L'étude a montré une réduction du risque relatif de 21% de progression ou de décès avec GRANITE par rapport au contrôle dans l'ensemble de la population traitée (HR=0,79). Dans le sous-groupe à faible ctDNA, une réduction du risque relatif de 38% a été observée (HR=0,62). La force des réponses des cellules T spécifiques aux néoantigènes chez les patients traités par GRANITE semble être associée à la survie sans progression. GRANITE a généralement été bien toléré, sans interruptions de traitement en raison d'événements indésirables. Les données sur la survie globale sont attendues pour le deuxième semestre 2025.
L'étude a inclus 104 patients randomisés, dont 69 dans l'analyse traitée. GRANITE a démontré un profil de sécurité favorable, les événements indésirables courants étant des effets systémiques et locaux légers associés à des vaccins puissants. Gritstone prévoit d'examiner les données PFS avec la FDA et de discuter des prochaines étapes, y compris un essai potentiel de phase 2 ou 3 utilisant les niveaux de ctDNA comme critère d'éligibilité.
Gritstone bio hat ermutigende Zwischenresultate der Phase 2 für GRANITE, seine individualisierte Neoantigen-gerichtete Immuntherapie, bei Behandlung des mikro-satelliten-stabilen kolorektalen Krebses (MSS-CRC) veröffentlicht. Die Studie zeigte eine relative Risikominderung von 21% bei Progression oder Tod im Vergleich zur Kontrollgruppe in der gesamten behandelten Population (HR=0,79). Im Low ctDNA-Subgruppen gab es eine relative Risikominderung von 38% (HR=0,62). Die Stärke der neoantigen-spezifischen T-Zell-Antworten der GRANITE-Patienten scheint mit dem progressionsfreien Überleben in Verbindung zu stehen. GRANITE wurde insgesamt gut vertragen, ohne Behandlungunterbrechungen aufgrund von Nebenwirkungen. Daten zum Gesamtüberleben werden für die zweite Hälfte von 2025 erwartet.
Die Studie umfasste 104 randomisierte Patienten, wobei 69 in die behandelte Analyse einbezogen wurden. GRANITE zeigte ein günstiges Sicherheitsprofil, wobei häufige Nebenwirkungen milde systemische und lokale Effekte waren, die mit potenten Impfstoffen assoziiert sind. Gritstone plant, die PFS-Daten mit der FDA zu überprüfen und die nächsten Schritte zu besprechen, einschließlich einer möglichen Phase 2 oder 3-Studie, die ctDNA-Spiegel als Zulassungskriterium verwendet.
- 21% relative risk reduction of progression or death with GRANITE vs. control in all treated population
- 38% relative risk reduction of progression or death with GRANITE vs. control in low ctDNA subgroup
- Strength of neoantigen-specific T cell responses associated with progression-free survival
- GRANITE was well-tolerated with no treatment discontinuations due to adverse events
- 33% of GRANITE patients remain on study and free of progression
- 12 of 13 GRANITE patients had stable ctDNA titers below the assay limit of quantitation
- Study not statistically powered for progression-free survival
- Continued follow-up needed to fully assess GRANITE effects
- 35 patients did not advance to study treatment after oxaliplatin
Insights
The interim Phase 2 data for GRANITE in frontline metastatic microsatellite stable colorectal cancer (MSS-CRC) shows promising results. Key findings include:
- 21% relative risk reduction of progression or death in the overall treated population (HR=0.79)
- 38% relative risk reduction in the low ctDNA subgroup (HR=0.62)
- Association between neoantigen-specific T cell responses and progression-free survival (PFS)
- Favorable safety profile with no treatment discontinuations due to adverse events
The data suggests potential efficacy, particularly in patients with lower disease burden. The 33% of GRANITE patients remaining progression-free, with 12 out of 13 showing stable ctDNA levels below quantitation limits, is encouraging. However, the wide confidence intervals indicate the need for further follow-up to confirm these trends.
The study's focus on MSS-CRC, typically resistant to immunotherapy, makes these results particularly intriguing. If confirmed, this could represent a significant advance in treating this challenging cancer type. The company's plans to discuss next steps with the FDA, potentially using ctDNA levels as eligibility criteria, align with the emerging trend of biomarker-driven patient selection in oncology trials.
From a financial perspective, these interim results could significantly impact Gritstone bio's market position and valuation:
- Positive data in MSS-CRC, a difficult-to-treat cancer, could expand GRANITE's potential market
- The engagement of Raymond James to explore strategic alternatives suggests potential for partnerships, licensing deals, or even acquisition interest
- The company's
$75.8 million market cap may be undervalued if GRANITE's efficacy is confirmed in larger trials
However, investors should note that further data maturation is needed and the wide confidence intervals indicate uncertainty. The expected overall survival data in 2H 2025 will be crucial. The company's exploration of "strategic and funding alternatives" suggests a need for additional capital to advance GRANITE, which could lead to dilution or other financial impacts.
While promising, these results are still early-stage. The stock may see increased volatility as the market digests this news and awaits further updates on GRANITE's development and potential strategic moves.
--Encouraging progression-free survival data in overall population; continued follow-up needed to allow data to mature further, especially in low ctDNA subgroup where events accrue more slowly
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-- Strength of neoantigen specific T cell responses in GRANITE patients appears to associate with progression-free survival
-- GRANITE was generally well-tolerated with no treatment discontinuations due to adverse events–
-- Overall survival data expected in 2H 2025 --
EMERYVILLE, Calif., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, today announced encouraging interim Phase 2 data from the ongoing Phase 2 study evaluating GRANITE, its individualized neoantigen targeting immunotherapy, in frontline microsatellite stable colorectal cancer (MSS-CRC). The randomized, controlled study is designed to evaluate the clinical benefit of maintenance therapy with GRANITE (GRT-C901/GRT-R902) in combination with immune checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone.
Overall progression-free survival (PFS) data show an encouraging benefit for GRANITE patients (HR=0.79 [
“We are excited by the potential of GRANITE to extend both progression-free and overall survival in a disease where relentless progression is the rule with existing therapies,” said Andrew Allen, MD, PhD, Co-Founder, President & CEO of Gritstone bio. “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 low ctDNA at study entry and thereby relatively low disease burden, could benefit from this type of immunotherapy. Success for immunotherapy typically 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 most recent ‘low and stable’ ctDNA measurements in most GRANITE patients are encouraging since that pattern is not typically seen in patients about to develop disease progression. The potential PFS benefit observed in MSS-CRC, a notoriously ‘cold’ tumor, suggests opportunity for even greater effects in tumors more typically amenable to immunotherapy.”
Dr. Allen continued, “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.”
Concurrently, Gritstone announced that it has engaged Raymond James as its financial advisor to support the Company in exploring and reviewing potential value-maximizing strategies. Gritstone does not intend to discuss or disclose further developments regarding the exploration of strategic alternatives unless and until its Board of Directors has approved a definitive action or otherwise determined that further disclosure is appropriate or required by law.
Key Findings from Interim Phase 2 Data in Front-Line Metastatic MSS-CRC
Data cut as of August 19, 2024
104 patients were randomized 1:1 in the study: 69 patients (39 GRANITE arm, 30 control arm) are included in the treated analysis below. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with the vast majority (
- Interim data demonstrated an emerging PFS benefit to all GRANITE recipients (study not statistically powered for PFS)
21% relative risk reduction of progression or death with GRANITE vs. standard of care (SOC) control in all treated population (HR=0.79 [95% CI, 0.42-1.50])33% (13/39) GRANITE and23% (7/30) of control patients remain on study and free of progression- Last ctDNA assessment is below the assay LOQ in 12/13 GRANITE and 4/7 control patients
- Clinical benefit was most notable in patients with low disease burden (defined as patients with ctDNA equal to or below the trial population median value at study entry)
38% relative risk reduction of progression or death with GRANITE vs. SOC control with low ctDNA subgroup (HR=0.62 [95% CI, 0.23-1.70])- Low baseline ctDNA is a likely prognostic and predictive factor
- Immune data were consistent with clinical activity
- Functional neoantigen-specific T cells were observed in all 16/16 GRANITE patients tested by ELISPOT
- Association of PFS and peak ex vivo ELISPOT responses was apparent, suggesting that ex vivo ELISPOT may be a surrogate for PFS
- GRANITE demonstrated a favorable safety and tolerability profile
- No patients discontinued study treatment due to an adverse event (AE)
- Common adverse events were the mild systemic and local effects associated with any potent vaccine, i.e. transient flu-like illness
- One treatment-related serious AE (fatigue) occurred in the GRANITE arm (patient continued GRANITE treatment without recurrence upon recovery)
Gritstone plans to review the PFS data with FDA in the coming months and agree on next steps to advance GRANITE, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.
About Gritstone bio
Gritstone bio, Inc. (Nasdaq: GRTS) is a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines. We leverage our innovative vectors and payloads to train multiple arms of the immune system to attack critical disease targets. Independently and with our collaborators, we are advancing a portfolio of product candidates to treat and prevent viral diseases and solid tumors in pursuit of improving patient outcomes and eliminating disease. www.gritstonebio.com
Gritstone Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to our clinical and regulatory development plans for our product candidates; our expectations regarding the data to be derived in our ongoing and planned clinical trials; our exploration of strategic alternatives; the timing of commencement of our future nonclinical studies, clinical trials and research and development programs; our ability to discover, develop and advance product candidates into, and successfully complete, clinical trials; and our plans and strategy regarding maintaining existing and entering into new collaborations and/or partnerships. Such forward-looking statements involve substantial risks and uncertainties that could cause Gritstone’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including Gritstone’s programs’ clinical stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Gritstone’s ability to successfully establish, protect and defend its intellectual property and other matters that could affect the sufficiency of existing cash to fund operations. Gritstone undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Gritstone’s most recent Annual Report on Form 10-K filed on March 5, 2024 and any subsequent current and periodic reports filed with the Securities and Exchange Commission.
Gritstone Contacts
Investors:
Tim McCarthy
LifeSci Advisors
tim@lifesciadvisors.com
Media:
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1AB
(973) 271-6085
dan@1abmedia.com
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