Abstract 612: The NCI exceptional responders initiatives: Initial feasibility result
Authors: Conley Barbara A. , Ivy S Percy , Tricoli James V. , Zenklusen Jean-Claude , Tarnuzzer Roy , Lubensky Irina , Takebe Naoko , Williams Paul M. , Zujewski JoAnne , Little Richard , White Jeffrey , Kohn Elise , Malik Shakun , Kim Ben , Souhan Erin , Staudt Lou 
Published: August 2015

Introduction: Preliminary data show that up to 10% of patients on early clinical trials have complete (CR) or partial (PR) responses. Exceptional responses (ER) are also observed in certain clinical cases using standard chemotherapy. The ERI Pilot study is evaluating the molecular alterations found in tumors from cancer patients who respond to a systemic treatment (standard or investigational) that is ineffective in at least 90% of patients. The study is available through the Cancer Trials Support Unit (www.ctsu.org). Experimental Procedures Cases of patients who achieve a CR or PR &gt; 6 months are proposed by email at NCIExceptionalResponders@mail.nih.gov. Once provisionally approved, the proposer sends tissue to a central repository, where the tissue is evaluated for percent tumor &necrosis; nucleic acids are isolated & sent for whole exome, mRNA & deep targeted sequencing. Tissue may be frozen or formalin fixed paraffin embedded but must be at least an entire core biopsy. Data will be correlated with mechanism of action of the treatment given. The ERI pilot study will characterize &gt; 100 ERs. If sufficient tissue is available, whole genome sequencing &other molecular analysis may be done. We anticipate that some specimens will not be of sufficient quality/quantity; thus many more tumors will need to be submitted to obtain these results. Six months after the genomic data are generated they will be released to a publicly available, controlled access database to facilitate research by qualified investigators. The ERI study accepts all types of malignant disease in adults or children if adequate tissue obtained prior to the ER exists. The ER could have been to an approved or investigational, targeted, or non-targeted systemic treatment. The feasibility of retrospectively collecting tumor tissue & clinical data for genomic analysis is a goal of the ERI study. Results: The ER study was activated on September 24, 2014. As of December 2, &gt; 80 cases have been proposed, 46 are provisionally approved & 26 cases were not ERs or were withdrawn. Accepted Cases: solid & hematologic tumors (2 brain, 4 breast, 2 colon, 6 gastric, 1 hepatocellular, 7 head/neck, 2 renal, 2 lung cancer, 1 melanoma, 2 ovarian, 6 pancreatic, 2 prostate and 4 sarcomas; 2 acute leukemia, 2 lymphoma, 1 myeloma). Approximately 75% involved standard & 25% involved targeted drugs or combinations. Tissue analysis is ongoing & results will be presented. Conclusions: Collection of archived tissue from ERs for genomic evaluation is feasible. Efficient ER case identification occurs through expert review and consensus-based case selection.

Citation Format: Barbara A. Conley, S Percy Ivy, James V. Tricoli, Jean-Claude Zenklusen, Roy Tarnuzzer, Irina Lubensky, Naoko Takebe, Paul M. Williams, JoAnne Zujewski, Richard Little, Jeffrey White, Elise Kohn, Shakun Malik, Ben Kim, Erin Souhan, Lou Staudt. The NCI exceptional responders initiatives: Initial feasibility result. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 612. doi:10.1158/1538-7445.AM2015-612