Background: UpRi is a first in class NaPi2b ADC with a novel scaffold-linker-payload that is designed to enable high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in HGSOC, with limited expression in healthy tissues. Interim data from a previous phase 1b study of heavily pretreated HGSOC patients reported clinical activity and tolerability data for UpRi as a monotherapy, most notably in patients with NaPi2b positive tumors (TPS≥75). Based on these emerging single-agent safety and efficacy data, it is hypothesized that UpRi in combination with carboplatin may provide additional clinical benefit for patients in earlier lines of treatment. UPGRADE-A is a Phase 1 dose escalation (DES) and expansion (EXP) study to evaluate UpRi and carboplatin followed by UpRi maintenance in recurrent platinum-sensitive HGSOC. The DES portion of UPGRADE-A has completed enrollment, and the EXP portion is ongoing. Methods: The EXP cohort of UPGRADE-A is enrolling patients with recurrent or metastatic PSOC (defined as having achieved a PR or CR to 4+ cycles in their last platinum containing regimen) who have received 1-3 prior lines of therapy. Up to 1 non-platinum based prior chemotherapy regimen is allowed, provided it is not the most recent line of chemotherapy. The primary objective of EXP is feasibility of UpRi + carboplatin at the RP2D, defined as 60% of patients completing at least 4 cycles of UpRi + carboplatin without discontinuing treatment early for reasons other than disease progression. Secondary objectives include the safety/tolerability, pharmacokinetics, and preliminary anti-neoplastic activity of the UpRi + carboplatin combination. Tumor tissue must be provided (archival or fresh sample) for retrospective NaPi2b assessment. UpRi 30mg/m2 + carboplatin (AUC 5) will be administered IV every 28 days for up to 6 cycles, followed by UpRi maintenance monotherapy until disease progression or unacceptable toxicity. Up to 30 patients are expected to enroll in EXP, and the trial is currently open for enrollment. NCT04907968. Clinical trial information: NCT04907968.