title: RRx-001-Induced Tumor Necrosis and Immune Cell Infiltration in an EGFR Mutation-Positive NSCLC with Resistance to EGFR Tyrosine Kinase Inhibitors: A Case Report.
abstract: We present the case of a 49-year-old male with metastatic epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma of the lung that continues to outlive stage IV diagnosis of non-small cell lung cancer after treatment with RRx-001, an experimental anticancer agent with epigenetic and immunologic activity, in the context of a phase II clinical trial called TRIPLE THREAT. Currently, no adequate treatment options exist for patients with EGFR mutation-positive tumors who have failed a 1st-generation tyrosine kinase inhibitor (erlotinib or gefitinib) treatment and do not develop a resistant mutation. Biopsy of a large pancreatic metastasis after RRx-001 demonstrated extensive necrosis with CD3+ and CD8+ immune cell infiltration that appears to correlate with prolonged survival despite end-stage disease. These results suggest that the mode of action of RRx-001 is related to immune stimulation in addition to epigenetic inhibition.
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Brzezniak
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Schmitz
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Peterson
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Aiste
authors.initials: A
authors.lastname: Degesys
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: Jan J
authors.initials: JJ
authors.lastname: Scicinski
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Scott Z
authors.initials: SZ
authors.lastname: Caroen
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
keywords: Epidermal growth factor receptor; Non-small cell lung cancer; RRx-001