HUTCHMED (China) Limited...today announces that AstraZeneca PLC (“AstraZeneca”) and HUTCHMED’s savolitinib has been granted conditional approval in China for the treatment of patients with non-small cell lung cancer (“NSCLC”) with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.

This was a single-arm, multi-cohort, multi-center, open-label, phase 3b study. Patients with advanced or metastatic treatment-naive METex14-mutated NSCLC were enrolled in Cohort 2 (1L), who received savolitinib... Median treatment duration was 8.02 months (range: 0.4, 14.5). Among evaluable patients with at least one post-baseline tumor assessment (n=84), the IRC-assessed ORR was 59.5%...The data showed an encouraging efficacy and a tolerable safety profile of savolitinib in 1L treatment for METex14-mutated NSCLC, suggesting a potential use of 1L treatment with savolitinib for this patient population.

Hutchison China MediTech Limited...announced that the China National Medical Products Administration (“NMPA”) has granted Priority Review status to the New Drug Application (“NDA”) for savolitinib for the treatment of non-small cell lung cancer (“NSCLC”) with MET Exon 14 skipping mutations.

...Histologically or cytologically documented locally advanced or Metastatic pulmonary sarcomatoid carcinoma (PSC) patients and other Non-small cell lung cancer（NSCLC） with MET Exon 14 mutation who have failed piror systemic therapy(ies), or are unwilling or unable to receive chemotherapy...

Median TTF of 1L savo mono in pts with MET ex14m was 12.6months and median TTF of savo plus osi in pts with resistant MET amp was 11.3 months….The real-world analysis results showed the promising clinical benefit of savo in NSCLC pts with MET alterations and the acceptable safety.

CONTRADICTING EVIDENCE:...46 (70%) patients had detectable baseline METex14, 24 of whom provided postbaseline samples within the first 6 weeks of savolitinib treatment....Patients with detectable baseline METex14 exhibited worse PFS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 0.88–3.57; p = 0.108] and OS (HR, 3.26; 95% CI, 1.35–7.89; p = 0.006) than those without….ctDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients with METex14-positive PSC and other NSCLC subtypes.

...the median OS (mOS) was 12.5 mo (95%CI 10.5-21.4) in FAS; 18-mo OS rate, 42.1%; 24-mo OS rate, 31.5%. In pre-treated and treatment naïve subgroups, 28.6% (12/42) and 46.4% (13/28) were PSC pts, respectively, and mOS was 19.4 mo (95%CI 10.5-31.3) and 10.9 mo (95%CI 7.5e14.0); 18-mo OS rate, 50.4% and 29.7%; 24-mo OS rate, 37.5% and 22.3%; respectively. In PSC and other NSCLC pts, mOS was 10.6 mo (95%CI 4.6-14.0) and 17.3 mo (95%CI10.6-23.6); 18-mo OS rate, 29.9% and 49.0%; 24-mo OS rate, 25.6% and 34.7%;respectively. Pts with brain metastases had mOS of 17.7 mo (95%CI 10.48-NA), 18-mOS rate 50.0% and 24-m OS rate 35.7%....The updated results further confirm the favorable benefit of savolitinib in pts with METex14+ NSCLC and each subgroup, and the acceptable safety profile.

...a multicenter phase II trial to evaluate the efficacy and safety of savolitinib 600 and 400 mg in Chinese patients with MET exon 14 altered NSCLC (n = 70)….Savolitinib showed an encouraging ORR in patients with MET exon 14 positive NSCLC, both in the tumor response evaluable set (N = 61; ORR 49.2% [95% CI 36.1–62.3]) and in the full analysis set (N = 70; ORR 42.9% [95% CI 31.1–55.3]).

Savolitinib yielded promising activity and had an acceptable safety profile in patients with pulmonary sarcomatoid carcinoma and other NSCLC subtypes positive for METex14 skipping alterations. 

...593 pts were pre-screened/screened, 87 identified with METex14+...Savolitinib was taken orally, once daily (QD) (600mg for weight ≥50kg or 400mg weight < 50kg) until disease progression or intolerable toxicity....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.

In the open-label phase 2 study, eligible pts received oral savolitinib at 600 mg...the median OS (mOS) was 12.5 mo (95%CI 10.5–21.4) in FAS; 18-mo OS rate, 42.1%; 24-mo OS rate, 31.5%. In pretreated and treatment naïve subgroups, 28.6% (12/42) and 46.4% (13/28) were PSC pts, respectively, and mOS was 19.4 mo (95%CI 10.5-31.3) and 10.9 mo (95%CI 7.5–14.0); 18-mo OS rate, 50.4% and 29.7%; 24-mo OS rate, 37.5% and 22.3%; respectively....The updated results further confirm the favorable benefit of savolitinib in pts with METex14+ NSCLC and each subgroup, and the acceptable safety profile.

...we present a case of a 65-year-old woman diagnosed with stage IIIA (cT2bN2M0, eighth TNM stage) upper right lung adenocarcinoma harboring MET exon 14 skipping alterations. After 4 weeks of therapy, a partial response was achieved with neoadjuvant savolitinib, and significant shrinkage in tumor and lymph nodes was observed.