Rare genitourinary tumors projects

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

1. ICONIC-A phase 2 study of Ipilimumab, CabOzantinib, and NIvolumab in rare genitourinary (GU) cancers (ICONIC) The phase 1 study of combination CaboNivo and CaboNivoIpi included patients with rare GU histologies. Objective responses were seen in patients with adenocarcinoma of the bladder/urachal, squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, penile cancer, sarcomatoid RCC, chromophobe RCC, and renal medullary carcinoma, leading to multiple rare tumor expansion cohorts. The final data for these rare tumors and the pooled data from the phase 1 and expansion cohorts are currently being analyzed. Based on these data, I initiated a phase 2 study through the Alliance cooperative group of CaboNivoIpi in patients with rare GU tumors which includes 12 cohorts: bladder squamous cell carcinoma, bladder small cell carcinoma, bladder adenocarcinoma, bladder plasmacytoid, bladder sarcomatoid, urethra (all histologies), penile cancer, sarcomatoid RCC, collecting duct RCC, renal medullary carcinoma, bone-only non-prostate GU tumor, and miscellaneous rare GU tumors. As of Preliminarily in this study we have seen confirmed responses in the bladder squamous cell carcinoma, bladder small cell carcinoma, bladder adenocarcinoma, urethra, penile cancer, sarcomatoid RCC, renal medullary carcinoma, and testicular adnexal carcinoma. An extensive number of translational correlatives are being conducted in this study with baseline and serial subsequent cycles of therapy. We will analyze the immune subsets of circulating PBMCs and ctDNA and use whole-exome sequencing to define the relationship between tumor mutational burden in each histologic subtype and response to the trial drugs. We will also use RNA sequencing to define the relationship between expression-based subtypes, the immune context of the tumors, and response to study drugs. Having a rare tumor clinical trial developed through the NIH and available nationally through a cooperative such as the Alliance builds on our center's recruitment strength and on our collaborative science. If this trial shows clinical activity, it may provide a potential new treatment option for patients with rare GU tumors. 2. Laser- A phase 2 study of Lurbinectedin +/-Avelumab in patients with small cell (and all neuroendocrine tumors) of the bladder and uppertract 3. SMART a phase 2 study of sacituzumab govitecan +/- atezolizumab in patients with: adenocarcinoma of the bladder/urachal, small cell (and all neuroendocrine tumors) of the bladder, squamous cell carcinoma of the bladder; renal medullary carcinoma; penile squamous cell carcinoma