RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials

Complete metabolic response of metastatic castration‐resistant neuroendocrine carcinoma of the prostate after treatment with RRx‐001 and reintroduced platinum doublets

“…High rates of initial responses to platinum doublets are followed inevitably by the development of intractable resistance. RRx‐001, a minimally toxic macrophage repolarizing agent with epigenetic properties, has been demonstrated to resensitize to previously tried and failed standard chemotherapies …”

“…RRx-001, a minimally toxic macrophage repolarizing agent with epigenetic properties, has been demonstrated to resensitize to previously tried and failed standard chemotherapies. 11 In the Phase II QUADRUPLE THREAT trial, RRx-001 is administered as a pretreatment or primer until progression in patients with four tumor types, SCLC, ovarian cancer, neuroendocrine, andepidermal growth factor receptor (EGFR) mutated NSCLC, prior to rechallenge with platinum doublets. RRx-001 is an epigenetic inhibitor and dual checkpoint inhibitor of CD47-SIRPα inhibition, which repolarizes M2like tumor-associated macrophages to M1-like macrophages.…”

A Recurrent Platinum Refractory Ovarian Cancer Patient With a Partial Response After RRx-001 Resensitization to Platinum Doublet

“…Biopsy of the patient’s tumors may help establish the specific epigenetic (or other) mechanism(s), for example, de-repression of silenced tumor suppressor genes and/or activation of the adaptive immune system by which resensitization to carboplatin occurred, the better to develop a predictive biomarker for prospectively determining which patients are most likely to benefit from rechallenge with platinum doublet after RRx-001 therapy. Rechallenge in platinum-resistant patients is theoretically not without risk, since the carboplatin-paclitaxel regimen, in particular, is associated with neuropathy and myelosuppression, which argues for the use of a predictive biomarker; however, even without such a biomarker, RRx-001, as a putative broad-spectrum dual chemoprotector and chemosensitizer, 11 may generally improve the therapeutic index of the doublet for unselected patients because of a better antitumor effect with lower toxicity. A pivotal or pivotal trials is required to confirm these hypotheses and to determine whether RRx-001 will be eventually added to the ovarian cancer armamentarium not only to reverse resistance in late recurrence but also potentially to prevent it in early-stage disease.…”

What's New in SCLC? A Review

“…RRx-001 is a minimally toxic tumor associated macrophage (TAM) and tumor associated neutrophil (TAN) repolarizing agent and pan-epigenetic inhibitor with orphan drug status in SCLC [36] . In over 170 patients treated to date over all studies in multiple tumor types including metastatic colorectal cancer, cholangiocarcinoma, as well as neuroendocrine, SCLC, EGFR mutated NSCLC and epithelial ovarian cancer, only one serious adverse event has been possibly attributed to RRx-001 as a single agent [37] .…”