3355 - Safety and Feasibility of Nimotuzumab Combined with Gemcitabine and SABR-Boosted Concurrent Radiotherapy for Muscle Invasive Bladder Cancer: Initial Results from a Phase I/II Trial

Purpose/Objective(s): Trimodality therapy (TMT) is recognized as a standard definitive treatment option for muscle invasive bladder cancer (MIBC). However, identifying a systemic regimen that combines potent radiosensitization with a favorable toxicity profile remains a challenge. Nimotuzumab, a humanized EGFR targeting antibody with intermediate affinity, theoretically offers a wider therapeutic index by sparing normal tissues while targeting EGFR overexpressing tumors. We report the initial safety results of a prospective Phase I/II trial (NCT07053735) evaluating Nimotuzumab combined with low dose Gemcitabine and concurrent radiotherapy.

Materials/Methods: Patients with cT2-4aN0M0 MIBC were prospectively enrolled. Following maximal TURBT, patients received a SABR boost (18 Gy in 3 fractions) to the tumor or tumor bed with a full bladder. Subsequently, conformal radiotherapy was delivered to the pelvic lymph nodes and empty bladder (45 Gy in 25 fractions). Concurrent systemic therapy consisted of weekly Nimotuzumab (200 mg, IV) and low dose Gemcitabine (100 mg per square meter, IV). The study planned to enroll 30 patients, a sample size providing over 95% statistical probability to detect any adverse event with a true incidence of 10% or greater. The primary endpoint was safety assessed by CTCAE v5.0. This initial report details the safety profile of the first 12 consecutive patients completing the full chemoradiotherapy course.

Results: As of February 2026, 20 patients have been enrolled with a median age of 68 years (range 47 to 85). Among them, 12 patients (11 males and 1 female) with a median age of 67 years (range 54 to 82) have completed the prescribed radiotherapy and concurrent systemic therapy. The safety analysis for these 12 patients revealed a distinct and manageable toxicity profile. Regarding non hematologic toxicity, Grade 3 or higher dermatitis and mucositis were absent (0/12). Grade 1 to 2 rash occurred in 2 (16.7%) patients, and no mucositis of any grade was recorded (0%). Nausea was observed in 6 (50.0%) patients, all of which were manageable with standard antiemetics. In terms of hematologic tolerability, Grade 3 to 4 leukopenia was observed in 2 (16.7%) patients, consistent with the expected pharmacodynamics of gemcitabine; however, no episodes of febrile neutropenia were reported, and all cases were effectively managed with GCSF support. Preliminary efficacy assessment is ongoing.

Conclusion: The combination of Nimotuzumab and low-dose Gemcitabine with concurrent radiotherapy demonstrated a manageable safety profile in this initial cohort. The regimen showed limited mucocutaneous toxicity and controlled hematologic events without febrile neutropenia. These preliminary findings support the continued accrual of this trial to further evaluate efficacy and safety.