Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+).

9519 Background: There are unmet medical needs for pts with METex14+ NSCLC. PSC is a rare type of NSCLC with high incidence of MET exon 14 mutations and poor prognosis. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective oral MET tyrosine kinase inhibitor, and its anti-tumor activity has been shown in combination with osimertinib in pts with EGFR-mutant, MET-amplified NSCLC (Yu H, et al. 2019 AACR, Abstract CT032). Methods: This was a multicenter, multi-cohort, single-arm phase II study (NCT02897479) to evaluate the efficacy, safety, and pharmacokinetics of savolitinib in pts with unresectable or metastatic METex14+ PSC and other NSCLC. MET mutation was tested or retrospectively confirmed by central laboratory. Savolitinib was taken orally, once daily (QD) (600mg for weight ≥50kg or 400mg weight < 50kg) until disease progression or intolerable toxicity. Tumor was evaluated every 6 weeks during the 1st year and every 12 weeks thereafter. The primary endpoint was independent review committee (IRC) assessed objective response rate (ORR) (RECIST version 1.1). Here we report the results of one cohort of prior MET-treatment naïve patients. Results: As of October 31, 2019, 593 pts were pre-screened/screened, 87 identified with METex14+ and 70 treated. Among treated pts, median age was 68.7 years (range 51.7-85.0), 58.6% pts were male, 92.9% stage IV, 60.0% previously treated, 57.1% with adenocarcinoma, 35.7% with PSC and the rest with other pathological types. Sixty-one pts were efficacy evaluable by IRC assessment (N = 61) (including pts who had at least one measurable lesion at baseline and had ≥1 scheduled post-baseline tumor assessment or evidence of any post-baseline radiological disease progression): ORR was 47.5% (95% CI: 34.6%, 60.7%), disease control rate 93.4% (95% CI: 84.1%, 98.2%) and median duration of response not reached yet. The median progression-free survival was 6.8 months (95% CI 4.2, 13.8) among all treated pts. Efficacy results were consistent with investigators’assessments. The most common (≥20%) treatment-related adverse events (TRAEs) were peripheral edema, nausea, increased AST/ALT, vomiting and hypoalbuminemia. The incidence of ≥ grade 3 TRAEs was 41.4%. TRAEs leading to treatment discontinuation occurred in 14.3% pts, among which liver injury and hypersensitivity were most common (each 2.9%). Conclusions: Savolitinib demonstrated promising anti-tumor activity and acceptable tolerability in METex14+ NSCLC pts. Clinical trial information: NCT02897479 .