3081 Background: TH1902 is a novel SORT1 targeting PDC. It exploits the natural function of SORT1, a scavenger receptor, which rapidly internalizes its natural ligands via endocytosis (internalization half-life ≤4 min). SORT1 is highly expressed in multiple solid tumors compared to normal healthy tissues making it an attractive target for rapid delivery of anti-cancer therapeutics. In this updated analysis, further data on long-term efficacy, safety and PK is presented from Parts 1&2 of Ph1 with focus on the 300 mg/m2 q3w. Due to safety observations in 6 patients (pts) enrolled at 420 mg/m2 dose level (Gr 3 neuropathy [n=2], Gr 4 neutropenia [n=2], Gr 3 ocular [n=1] and Gr 2 skin [n=3] toxicities, the dose was reduced to 300 mg/m2 in Part 2. Methods: Primary objective of the study was to characterize the safety/tolerability of TH1902. Part 1 (modified intrapatient dose escalation) included pts with recurrent/refractory advanced solid tumors (all comers) with no limit on number of previous therapies, including taxanes. Part 2 (dose expansion) included pts with known high SORT1 expression (e.g. OVC, endometrial, TNBC, melanoma). Results: Twenty-five heavily pretreated pts were enrolled in the 300 mg/m2 group. At least one TRAE was observed in 80% of pts. Grade 3 (Gr 3) events of interest were neuropathy (12%), keratitis (8%), anemia (8%), and neutropenia (4%), for an overall incidence of 32%. All grade neuropathy was 28%. Most TRAEs were mild to moderate severity and manageable with standard supportive care or dose reductions. Safety profile of TH1902 was different from that of docetaxel. PK measures of Cmax and AUC showed that exposure to free docetaxel was much lower than that of TH1902; Cmax = 0.58 μM for free docetaxel vs 30.4 μM for TH1902 and AUC24 = 3.1 h.nmol/mL for free docetaxel vs 74.8 h.nmol/mL for TH1902. Three pts exhibited RECIST 1.1 confirmed long-term stabilizations of disease, even after drug discontinuation, which ranged from 8 to 19 mos from treatment initiation, of which one OvC pt had overall PR (with RECIST 1.1 confirmed CR in target lesions) and remained on treatment for a total of 5 months. In addition, one endometrial cancer (part 1) was dose escalated from 60-360 mg/m2 and completed 11 cycles in total. Pt remained in SD during the 8 mos of treatment, up to time of consent withdrawal. All 4 pts had prior taxane exposure. Conclusions: TH1902 induces durable disease stabilization that lasts beyond treatment completion, suggesting a unique, multimodal mechanism of action (MOA) that differs from other cancer therapeutics. TH1902 has a manageable safety profile at 300mg/m2 with few Gr3 AEs. Low levels of free docetaxel in human plasma may in part explain the low rate of taxane related AEs (i.e. neutropenia, no alopecia). Next phase of the study involves dose optimization to further limit toxicity and improve efficacy. Clinical trial information: NCT04706962 .