Guard-01: A randomized, open-label trial of efbemalenograstim alfa as primary prophylaxis for neutropenia during definitive concurrent chemo-radiotherapy.

12060 Background: Concurrent chemoradiotherapy (CCRT), a curative cornerstone for locally advanced malignancies, exerts synergistic antitumor efficacy but is frequently hampered by severe hematologic toxicity (mainly neutropenia), leading to treatment delays, dose reductions and compromised outcomes. GM-CSF, previously evaluated for CCRT-induced hematologic AE prophylaxis, is no longer recommended due to increased immune-related toxicities and limited efficacy. While G-CSF is safe in chemotherapy, high-quality data for long-acting G-CSF as primary CCRT prophylaxis is sparse, creating a critical clinical gap that the Guard-01 study aims to resolve. Methods: This multicenter, randomized, open-label, controlled trial plans to enroll 120 patients undergoing definitive CCRT for locally advanced malignancies. Eligible participants are randomized 1:1 to either the study arm or control arm, stratified by chemotherapy regimen. Study arm patients receive efbemalenograstim alfa ~48 (±4) h post each chemotherapy cycle; control arm patients receive no primary G-CSF prophylaxis, with secondary efbemalenograstim alfa permitted for febrile neutropenia (FN) or dose-limiting neutropenia. The primary endpoint is the incidence of grade 3/4 neutropenia across the entire CCRT course. Results: As of December 2, 2025, 122 patients were enrolled (60 study arm, 62 control arm). The incidence of grade 3/4 neutropenia during the entire treatment course was 16.67% in the study arm versus 53.23% in the control arm, with a significant between-group difference of -36.56% (90% CI: -48.98%, -22.84%; p < 0.0001). Rates were significantly lower in the study arm across the first (5.00% vs. 45.16%; p < 0.0001) and second (12.28% vs. 27.27%; p = 0.0393) chemotherapy cycles. Consistent benefit was observed in subgroup analysis, with a significant difference in paclitaxel- or pemetrexed-based regimens (20.00% vs. 64.52%; p = 0.0004). The study arm had shorter grade 3/4 neutropenia duration (0.62±1.57 vs. 3.27±4.84 days; p < 0.0001) and higher ANC nadir (2.82 vs. 0.94 ×10⁹/L; p < 0.0001). No neutropenia-related chemotherapy dose reductions or discontinuations occurred in the study arm, compared with 6.45% dose reductions and 1.61% discontinuations in the control arm. The most common TEAEs in the study arm were anemia (71.67%), thrombocytopenia (60.00%), and leukopenia (35.00%). Grade ≥3 TEAEs were less frequent in the study arm (41.67% vs. 64.52%), with no grade ≥3 TRAEs reported in either group. Exploratory endpoints include 2-year PFS and OS, with immature data pending longer-term follow-up. Conclusions: Efbemalenograstim alfa significantly reduces the incidence and duration of grade 3/4 neutropenia in patients undergoing definitive CCRT, with consistent efficacy across different chemotherapy regimens and a favorable safety profile. Clinical trial information: ChiCTR2300077504 .