Eligible patients must have advanced/metastatic clear cell/papillary renal cell carcinoma (RCC; ≥2 prior therapies including VEGF-TKI) or clear cell ovarian carcinoma (OCCC; ≥1 platinum-taxane regimen), measurable disease, life expectancy ≥3 months, and available TIM-1-expressing tumor tissue. Key exclusions: prior MMAE therapy, recent cytotoxic/TKI/mAb treatments (within 2-4 weeks), uncontrolled comorbidities, active infections (excluding oral-therapy-controlled cases), untreated brain metastases, significant cardiovascular disease, concurrent malignancies (except cured skin/in situ cancers), and chronic high-dose corticosteroid use (>5mg prednisone/day). Effective contraception is mandatory during and for 6 months post-treatment.

The dose escalation phase aims to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of CDX-014, defined as the highest dose with <33% incidence of dose-limiting toxicities (DLTs) within 21 days post-first dose. The expansion cohort will evaluate objective response rate (ORR) per RECIST v1.1, assessed every 6-9 weeks until discontinuation or progression (up to 5 years).

Advanced clear cell or papillary renal cell carcinoma (RCC) who experienced progression after at least two lines of systemic therapy, including at least one TKI were included; Additional main inclusion criteria included measurable disease by Response Criteria in Solid Tumors (RECIST) 1.1 criteria, a Karnofsky performance status 70%, and adequate renal, hepatic, and hematological laboratory values.

One patient (6.20%) treated at 0.3 mg/kg every 3 weeks exhibited PR as best overall response,ongoing after 17 months on therapy; this patient had been on single agent PD-1 inhibition prior to initiating therapy with CDX-014. Five patients (31.00%) exhibited clinical benefit from CDX-014. PFS and OS were 2.70 months (95%CI 1.2-8.0) and 12.6 months (95%CI 5.7-12.6),respectively.