A Phase Iii Trial-In-Progress Called Replatinum That Compares Rrx-001+A Platinum Doublet To A Platinum Doublet In Third-Line Or Beyond Small Cell Lung Cancer.

TPS9083 Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RRx-001 is a first-in-class, minimally toxic small molecule immunotherapeutic that inhibits c-Myc, downregulates the antiphagocytic checkpoint, CD47, repolarizes tumor associated macrophages (TAM) from protumor M2 to antitumor M1 and resensitizes to previously active first line therapies. On the basis of favorable results from a Phase 2 trial called QUADRUPLE THREAT (NCT02489903) in combination with a platinum doublet in later line SCLC, a Phase 3 trial called REPLATINUM was started in 3rd line or beyond SCLC in Q4 2019. Enrollment is ongoing. Methods: This US-based, open-label, randomized, phase 3 study (NCT03777657) compares RRx-001 4mg + a platinum doublet (carboplatin or cisplatin + etoposide) versus a platinum doublet for pts with 3rd line or beyond SCLC that have previously received a checkpoint inhibitor. Approximately 120 pts from 25 centers will be randomized 1:1 to receive RRx-001 4 mg in combination with a platinum doublet vs. a platinum doublet. The platinum doublet will be administered on both arms for up to 4 cycles; on the RRx-001 arm only patients with stable disease or better are eligible to continue on RRx-001 4 mg + carboplatin AUC 2-4 maintenance therapy. If radiologic progression occurs on the control arm prior to the 4th cycle, patients are eligible to crossover to the RRx-001 treatment arm. PFS is the primary endpoint. Secondary endpoints include OS and ORR. Exploratory endpoints include c-Myc, CD-47 and PD-L1 on circulating tumor cells and SIRP-alpha expression on circulating monocytes. Clinical trial information: NCT03777657.