Celldex Therapeutics starts phase 1/2 trial of CDX-014 in advanced renal cell carcinoma

TIM-1 expression is upregulated in several cancers, most notably renal cell and ovarian carcinomas, and is associated with a more malignant phenotype of RCC and tumor progression. TIM-1 has very restricted expression in healthy tissue. The study is open to patients with both clear cell and papillary RCC.

"Although significant advances have been made in the treatment of metastatic renal cell carcinoma, patients who progress through currently approved therapies have extremely limited options," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics.

"Selectively targeting TIM-1, which is expressed in the majority of metastatic renal cell carcinomas, presents a novel approach that could provide new options for patients. CDX-014 has also demonstrated an ability to effectively kill tumor cells without negatively impacting immune response in preclinical studies, which may make it an ideal candidate for future combination therapy. We are pleased to initiate this first study of CDX-014, further broadening our pipeline to meet the needs of patients with difficult to treat cancers."

The Phase 1 dose-escalation portion of the study will evaluate cohorts of patients receiving increasing doses of CDX-014 to determine the maximum tolerated dose and a recommended dose for Phase 2 study. The Phase 2 portion of the study will enroll approximately 25 patients to assess the anti-tumor activity of CDX-014 at the recommended dose in advanced renal cell carcinoma as measured by objective response rate (RECIST 1.1).

Secondary objectives include safety and tolerability, pharmacokinetics, immunogenicity and additional measures of anti-tumor activity, including clinical benefit rate.

The study is being conducted in the United States and is expected to include approximately 10 sites. Patients must have advanced/metastatic clear cell or papillary renal cell carcinoma and have experienced progressive disease after at least two prior lines of therapy, including at least one VEGF-targeted tyrosine kinase inhibitor, or be otherwise inappropriate candidates for all approved therapies. Data analysis will be conducted separately in clear cell RCC and papillary RCC, as well as by the total population.

About CDX-014

CDX-014 is a fully human monoclonal antibody-drug conjugate (ADC) that targets T-cell immunoglobulin mucin-1 (TIM-1). TIM-1 expression is upregulated in several cancers, most notably renal cell and ovarian carcinomas, and has very restricted expression in healthy tissue. The TIM-1-targeting antibody, CR014, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology.

CDX-014 is designed to be stable in the bloodstream, but to release MMAE upon internalization into TIM-1-expressing tumor cells, resulting in a targeted cell-killing effect. CDX-014 is in development for the treatment of advanced/metastatic clear cell or papillary renal cell carcinoma.