MA11.06 A PII Study of Toripalimab, a PD-1 mAb, in Combination with Chemotherapy in EGFR+ Advanced NSCLC Patients Failed to Prior EGFR TKI Therapies

EGFR TKI is the standard 1st line therapy for the patients with advanced NSCLC harboring EGFR mutations. While PD-1 checkpoint blockade has become an integral component of disease management for EGFR wild type NSCLC patients at various settings, platinum-based chemotherapy is still the standard of care for EGFR mutated NSCLC pts who progressed after EGFR targeting therapy. Early attempts to combine EGFR TKI with checkpoint blockade had resulted in exacerbated immune related toxicity in the lung. Here we aimed to prospectively evaluate toripalimab, a humanized PD-1 mAb approved for 2nd line treatment of melanoma, in combination with chemotherapy to treat EGFR mutated NSCLC patients failed to EGFR TKI therapies. This is a phase II, multicenter, open-label, single-arm study for pts with EGFR activating mutations who have failed prior EGFR-TKI therapies without T790M mutation or failed osimertinib treatment. Pts were treated with 240mg or 360mg fixed dose toripalimab once every 3 weeks in combination with carboplatin and pemetrexed for up to 6 cycles, followed by toripalimab plus pemetrexed maintenance therapy until disease progression or intolerable toxicity. Primary endpoint was objective response rate as assessed by investigator per RECIST v1.1 once every 6 weeks. Forty pts were enrolled from Apr 25, 2018 to March 22, 2019 with 52.5% female patients and a median age of 57. 57.5% pts harbored EGFR exon19 deletion while 42.5% pts had exon21 L858R mutation. Only 1 pt had T790M mutation who progressed after osimertinib treatment. As of Apr 3 2019, among 31 evaluable pts, 17 partial response and 12 stable disease were observed for a 54.8% ORR (95% CI, 36.0% to 72.7%) and a 93.5% DCR (95% CI, 78.6% to 99.2%). Median PFS was 7.6 months, while median DOR was not reached. Treatment emergent adverse events (TEAE) occurred in 86.5% of the pts, grade 3 or higher events occurred in 51.4% of patients including one death. Most common AE included leukopenia, neutropenia, thrombocytopenia, anemia, nausea, and loss of appetite. Treatment discontinuation due to AE occurred in 10.8% of the pts. Anti-PD-1 mAb, toripalimab in combination with carboplatin and pemetrexed has shown a promising anti-tumor efficacy with a tolerable safety profile for advanced NSCLC patients with EGFR mutated who progressed after EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). A phase III registration study will be initiated in May 2019. (Clinical trial information: NCT03513666)