title: Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization.
abstract: RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first- or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types - non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors - prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to 'episensitize' tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival.
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Oronsky
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Scott Z
authors.initials: SZ
authors.lastname: Caroen
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Scicinski
authors.affiliation: Department of Bioengineering, University of California, La Jolla, Calif., USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.affiliation: Moores Cancer Center, University of California and San Diego, La Jolla, Calif., USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Reid
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Aiste
authors.initials: A
authors.lastname: Degesys
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: John
authors.initials: J
authors.lastname: Jenkins
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Brzezniak
keywords: Non-small cell lung cancer; Partial response; Platinum doublets; RRx-001; Refractory EGFR