Dataset Information

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.

SUBMITTER: Brzezniak C

PROVIDER: S-EPMC4748757 | biostudies-literature | 2016 Jan-Apr

REPOSITORIES: biostudies-literature

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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.

Brzezniak Christina C Schmitz Bruno A BA Peterson Paul G PG Degesys Aiste A Oronsky Bryan T BT Scicinski Jan J JJ Caroen Scott Z SZ Carter Corey A CA

Case reports in oncology 20160115 1

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 ...[more]

PMID: 26933418

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Project description:IntroductionThe current standard of care for newly diagnosed glioblastoma (GBM) is maximum surgical resection followed by concurrent treatment with temozolomide (TMZ) and radiotherapy (RT) and then six to twelve cycles of maintenance TMZ. RRx-001, an NLRP3 inhibitor and nitric oxide (NO) donor with chemoradiosensitizing, vascular normalizing and macrophage repolarizing properties, is currently in a Phase III trial for small cell lung cancer (SCLC). The purpose of this non-randomized trial was to establish the safety and look for a signal of clinical activity of RRx-001 as an add-on to RT and TMZ in patients with newly diagnosed glioblastoma.MethodsIn this non-randomized, open-label, two part trial called G-FORCE-1 (NCT02871843), the first four cohorts of adult patients with histologically confirmed high grade gliomas received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and escalating doses of once weekly RRx-001 from 0.5 mg to 4 mg according to a 3+3 design followed by a 6 week no treatment interval and then standard maintenance TMZ (150 mg/m2 Cycle 1 and 200 mg/m2 in subsequent cycles) until disease progression. The second two cohorts of patients received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and once weekly RRx-001 4 mg followed by a 6 week no treatment interval and then two different maintenance schedules until disease progression according to the same 3+ 3 design: 1. 0.5 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/week for up to 6 cycles of therapy; 2. 4 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/week for up to 6 cycles of therapyThe primary endpoint was the recommended dose/maximally tolerated dose of the combination of RRx-001, TMZ and RT. Secondary endpoints were overall survival, progression free survival, objective response rate, duration of response and clinical benefit response.ResultsA total of 16 newly diagnosed glioblastoma patients were enrolled. No dose limiting toxicities were observed and no MTD was reached. The recommended dose is 4 mg. After 24 months of follow up the median OS was 21.9 months (95% CI: 11.7 - NA). PFS median was 8 months (95% CI: 5 - NA). The overall response rate was 18.8% (3 PR out of 16) and the disease control rate was 68.8% (3 PR, 8 SD out of 16).ConclusionsThe addition of RRx-001 to TMZ and RT and to TMZ during maintenance was safe and well-tolerated and deserves further study.

Dataset Information

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.

Publications

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.

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