382MO The preliminary safety result of a phase II study of osimertinib in combination with platinum + pemetrexed in patients with previously untreated EGFR-mutated advanced NSCLC (NEJ032C/LOGIK1801: OPAL)

Based on the result of the FLAURA trial, osimertinib (OSI) is a standard of care in patients (pts) with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). One of the promising strategies to further improve pts' outcome is a combination therapy with OSI and platinum-doublet chemotherapy. An ongoing multicenter phase II study is assessing the safety and efficacy of OSI + cisplatin (CDDP)/carboplatin (CBDCA) + pemetrexed (PEM) in previously untreated pts with EGFR-mutated NSCLC. A total of 67 pts were enrolled in arm A (CDDP) or arm B (CBDCA) at the discretion of each investigator. In addition to OSI 80 mg administered orally daily, CDDP (75 mg/m2)/CBDCA (AUC=5) and PEM (500 mg/m2) were administered intravenously every 3 weeks for up to 4 cycles. Pts without disease progression (PD) after 4 cycles of induction therapy continued OSI + PEM until PD or unacceptable toxicity. The co-primary endpoints are safety and objective response rate, and the secondary endpoints include complete response rate, disease control rate, and progression-free survival. As of 25 Feb 2020, 67 pts (34 in arm A; 33 in arm B) were enrolled: (median age 67 [range, 26-75] years; 43 female [64.2%]; 46 ECOG PS 0 [68.7%]; 66 adenocarcinoma [98.5%]; 31 EGFR ex19del [46.3%], 35 ex21 L858R [52.2%], 1 both [1.5%]). At the data cut-off (31 Mar 2020), 11 pts (16.4%) discontinued treatment: 2 (3.0%) due to PD; 6 (9.0%) adverse event (AE); 3 (4.5%) pts' withdraw. At least one dose reduction was required in 41.2% (arm A) and in 57.6% (arm B). Most common (>5%) Grade 3≥ AEs were neutropenia (37.3%), lymphocyte count decreased (29.9%), white blood cell decreased (25.4%), platelet count decreased (19.4%), anemia (17.9%), anorexia (7.5%) and alanine aminotransferase increased (6.0%). One patient in arm B experienced grade 4 QT prolongation and terminated protocol treatment. This is the first study to explore the efficacy and safety of OSI in combination with platinum-based chemotherapy as the first line treatment. This combination treatment has been well tolerated and follow-up is ongoing.