Background: SORT1 is expressed in a variety of tumors when compared to most healthy tissue. TH1902 is a first-in-class PDC targeting SORT1, that consists of 2 molecules of docetaxel attached to the TH19P01 peptide via a cleavable succinyl linker. Conjugating the short peptide with various anti-cancer agents allows for targeted delivery of payloads to the tumor. Here we report results from Part 1 of a FIH, multicenter, phase 1 study, designed to explore the safety, pharmacokinetics (PK) and efficacy of TH1902 in advanced solid tumors. Methods: Part 1 used a modified rapid intrapatient dose escalation design. A starting dose of 30 mg/m² Q3W of TH1902 was used for the study based on the available pre-clinical data of TH1902 and the known safety profile of docetaxel. Eligibility criteria included pts with advanced solid tumors (all-comers) that have relapsed or are refractory to standard anticancer treatment. Pts had no limit on previous lines of therapy, and were required to have measurable disease by RECIST, expected survival of ≥3 months, ECOG 0-1, and adequate organ function. Pts were not required to be tested for SORT1 at entry. The primary objective of the study was to characterize the safety and tolerability of TH1902. The primary objective of Part 1 was to identify the maximum tolerated dose and the recommended dose for Part 2 (dose expansion). Additional objectives included the examination of the PK of TH1902 and free docetaxel, and outcomes as related to SORT1 expression. Results: As of April 2022, 18 pts were enrolled in Part 1 and included 6 ovarian, 1 endometrial, 1 cervical, 3 prostate, 3 ER+/Her2+ BC, 3 melanoma and 1 NSCLC. Pts received an average of 8 prior regimens (range: 3-20). All pts received at least 1 dose of study drug and were evaluated after the 1^st cycle for a DLT. Dose levels between 30-420 mg/m² Q3W were studied. Following safety observations among the 6 patients enrolled at the 420 mg/m² dose level (Gr 3 neuropathy [n=2], Gr 4 neutropenia [n=2], Gr 3 ocular [n=1] and Gr 2 skin toxicities), the dose was reduced to 300 mg/m². At the at 300 mg/m² cohort, seven pts received a mean of 2.9 cycles. AEs (regardless of relatedness) occurred in all 7 (100%) pts, mostly Gr 1-2. One pt had Gr 3 worsening anemia (probably related) and Gr 3 abdominal pain/fistula (unrelated). AEs of interest were all Gr 1-2, and included: ocular (keratitis/dryness)=2 pts; GI (nausea/vomiting/diarrhea)=2 pts; neuropathy=2 pts; MSK (arthralgia/myalgia/extremity pain)=2 pts. In 15 evaluable pts in Part 1 clinical benefit was observed in 10 pts: 1 PR (prostate with 53% decrease in target lesion) and 9 SD. PK and SORT1 expression analyses are ongoing. Conclusions: Although biological activity has been observed, the optimal dosing regimen of TH1902 is currently under evaluation. Clinical trial information: NCT04706962.