Gritstone bio Announces Positive Preliminary Progression-free Survival and Long-term Circulating Tumor DNA (ctDNA) Data from Phase 2 Portion of Ongoing Phase 2/3 Study of its Personalized Cancer Vaccine, GRANITE, in Front-line Metastatic Microsatellite St - Seite 3

Key Findings from Preliminary Phase 2 Data in Front-Line Metastatic MSS-CRC
Clinical data cut as of March 8, 2024; ctDNA data cut as of March 12, 2024

One hundred and four (104) patients were randomized (1:1) in the study: Sixty-seven (67) patients (39 GRANITE arm, 28 control arm) are included in the treated analysis below. Thirty-six patients have 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 (PFS)

• Early trend in PFS benefit was observed for GRANITE recipients
  • Hazard ratio of 0.82 ([95% CI, 0.34-1.67]; 62% censored) in all patients
  • Hazard ratio of 0.52 ([95% CI, 0.15-1.38]; 44% censored) in high-risk patients¹ (>90% have liver metastases). Median PFS of 12 months (GRANITE) vs. 7 months (control).
    • ¹High-risk subgroup defined as baseline ctDNA above the median value (2%) for the control group (ctDNA quantified as mean variant allele frequency [VAF] at time of study randomization). This analysis was performed on 44 patients who received study treatment (control and GRANITE arms) and have available baseline ctDNA data.
  • GRANITE and control arms begin separating 1-2 months after initiation of GRANITE treatment, consistent with expected kinetics of GRANITE-induced immune response
    

Biomarker Results – Circulating Tumor DNA (ctDNA)

• Short-term molecular response (>30% reduction in ctDNA using single time-point analysis, defined per protocol) is uninformative due to unanticipated continuation of ctDNA drop beyond induction chemotherapy.
  • Molecular response, similar in both arms (30% [6/20] in vaccine arm; 42% [5/12] in control arm)
• Long-term ctDNA responses align with PFS trends and favor GRANITE vs. control patients
  • Analysis in the high-risk group¹ shows that between first blood draw (time of randomization) and last blood draw (most recent study visit), ctDNA shifted from high (>2% VAF) to low (≤2% VAF) in 56% (9/16) of GRANITE patients vs 22% (2/9) of control patients. Progressive disease was observed in 44% (7/16) vs 78% (7/9), respectively, within this group.
  • Analysis in patients whose ctDNA was negative after induction chemotherapy, a low-risk group, favors GRANITE. Sustained ctDNA negativity was observed in 67% (6/9) of GRANITE recipients vs 38% (3/8) control patients. Progressive disease was observed in 11% (1/9) and 38% (3/8) of these patients, respectively.