P2.06-031 QUADRUPLE THREAT: A Pilot Phase 2 Study of RRx-001 in Advanced Lung Cancer Prior to Re-Administration of Platinum Doublets: Topic: Supportive, Preventive

The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. RRx-001, an epi-immunotherapeutic agent, may resensitize patients to previously effective, now refractory therapies, potentially improving survival. This study (NCT02489903) explores the potential of RRx-001 to sensitize patients who previously responded and now have failed a platinum based doublet to the previously effective therapy. In this 4-arm, 3-stage study, subjects with SCLC, NSCLC, HGNEC and ovarian cancer (EOC) in each arm receive RRx-001 weekly until progression followed by platinum therapy. Each cohort will initially enroll 3 patients to assess for safety (Stage 1) then 7 patients (Stage 2) for a total of 10 patients per cohort. If any arm has ≥ 1/10 subjects that has stable disease or better, then additional patients would be enrolled in that arm (Stage 3) for totals of 31 (NSCLC), 26 (SCLC), 26 (HGNEC) and 26 (EOC). Eligibility criteria include: evaluable, progressive disease; previous response to platinum doublet therapy; ECOG PS ≤2. Primary endpoint is Overall Survival with ORR, DCR, PFS and rate of toxicity for reintroduced platinum therapy as secondary endpoints. Exploratory pathologic assessments, including oncogenic mutation expression and infiltrating tumor lymphocyte analysis, will be performed on tumor samples before and after starting the study regimens. Stage 1 for all arms except EOC has been completed with no unexpected AEs. RRx-001 treatment to date resulted in a 45% (5/11) DCR including one Partial Response in HGNET. Reintroduction of platinum therapy in evaluable patients with SCLC and NSCLC resulted in an ORR of 75% (3/4), and 67% (2/3), respectively (HGNET and EOC: 0 evaluable). Median OS for all patients is 7.0 mo. (7.8 mo. median f/u). One patient with resistant SCLC had a confirmed Partial Response to cisplatin/etoposide and his treatment free interval post platinum was >180 days. To date, serial on-treatment biopsies have demonstrated an increase in T-cell tumor infiltration over time. Recruitment to this study is continuing. Although the trial is ongoing, early data suggest that RRx-001 appears to increase the sensitivity of SCLC and NSCLC to subsequently reintroduced carboplatin or cisplatin (to date no HGNCEC and EOC patients have been rechallenged with platinum). In addition, data from one patient indicates a conversion of resistant to sensitive SCLC phenotype. These data suggest that RRx-001 priming may lead to a new treatment strategy resulting in renewed sensitivity to chemotherapy and prolongation of survival.