e16151 Background: Fibrolamellar Carcinoma (FLC) is a rare form of primary liver cancer affecting teenagers and young adults without any underlying liver disease. It typically presents at an advanced stage with a mix of symptoms attributed to other causes. Currently R0 resection is the only cure. One-half of patients are unresectable at presentation with short life expectancies. An effective neoadjuvant therapy that could increase resectable patients and a sustained response. Although a few FLC-specific clinical trials have been ongoing for several years, there are no published results yet, nor expected for several years. Gemcitabine-oxaliplatin-lenvatinib (GOL) was selected based on case reports of GO success and trials using GO with sorafenib (SOR), but with LEN substituted for SOR based on superior efficacy and lower toxicity. This the largest cohort of FLC patients receiving the same systemic therapy reported. Methods: After approval (#IRB00003999) and consent (NCT03793088), data was collected on all GOL subjects from April 15, 2019 to Jan. 31, 2024. Response was measured using RECIST 1.1 and volume estimates. Results: Sixty-five GOL courses, 60 patients (30F), 5 retreated, median age at diagnosis/start of GOL (19/21), 58 unresectable, previous surgeries/relapses/therapies (1/2/2), stage I/II/III/IV (0/1/4/60) were given GOL cycles (median 10) of G:1000mg/m2,O:100mg/m2,L:8mg daily, 98% neoadjuvantly. Excluding the 14 on GOL, 3 with planned and 3 who refused surgery, 28 of 39 (72%) have had surgery (R0=20, R2=6, transplant=2), leaving 11 still unresectable. Twelve had > 6 lymph nodes examined with 75% showing < 1 positive for microscopic disease. The median time to best response was 4.7 months and 9.8 cycles with RECIST and volume best responses of: -21% and -41%. Complete/partial/stable/progressive responses by RECIST and volume were 1/12/45/1 and 2/18/38/1, for an overall response/disease control rate of: 22% / 98% and 34%/97%. Circulating DNA prospectively followed had an average drop of -93%, with one-third achieving 0.0 at completion of GOL. The 6,12,18 and 24 month overall survival from the start of GOL is (%): 97/87/73/65. To date, 38 have failed GOL, including: death (37%), infection (5%), or alive post relapse (19%) at a median time from start of GOL of 12 months. Although these are high-risk patients (median 3 relapses) 67% had their longest disease-free interval. The most common toxicities were neuropathy (39%), cytopenias (10%), and nausea (10%), mostly (95%) NIH grade 1 or 2. Conclusions: Our retrospective study of high-risk FLC, most multiply relapsed, pretreated, stage 4 and unresectable, showed that a prolonged and meaningful clinical response and acceptable quality of life with a chance for curative surgery is possible for many young patients thought to be incurable. Prospective trials are needed to confirm these results.