The Center for Drug Evaluation, of the National Medical Products Administration in China, has granted a breakthrough therapy designation to savolitinib for use in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction with MET amplification in whom at least 2 lines of standard therapy have failed.
The Center for Drug Evaluation, of the National Medical Products Administration (NMPA) in China, has granted a breakthrough therapy designation (BTD) to savolitinib for use in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) with MET amplification in whom at least 2 lines of standard therapy have failed.1
The safety and efficacy of the oral MET TKI is under exploration in this patient population, as part of a single-arm, multi-arm, open-label, phase 2 trial (NCT04923932).2
“NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies,” according to a press release issued by HUTCHMED (China) Limited, one of the drug developers.1 “Drug candidates with BTD may be considered for conditional approval and priority review when submitting a new drug application.”
The phase 2 trial is currently recruiting patients who are at least 18 years of age who have histologically diagnosed locally advanced or metastatic gastric cancer and esophagogastric junction adenocarcinoma with MET amplification.2
Those in cohort 1 need to have measurable lesions by RECIST v1.1 criteria, and those in cohort 2 need to have evaluable lesions. Patients also need to have an ECOG performance status of 0 to 2; estimated survival of at least 12 weeks; and acceptable bone marrow, liver, and kidney function.
Patients who had other malignant tumors or other infiltrating malignant tumors in the past 5 years were excluded, as were those with stage I malignant tumors following radical treatment for at least 3 years apart from those with a possibility of disease recurrence. Patients also could not have received prior treatment with chemotherapy, hormone therapy, biotherapy, immunotherapy, or traditional Chinese medicine for an antitumor indication within 3 weeks before study treatment initiation. If they previously received small molecule TKIs in the 2 weeks before the start of savolitinib on the trial, they were also excluded.
Study participants will receive savolitinib at 600 mg daily, continuously, in those who weigh 50 kg or more at baseline. For those who have baseline weight of less than 50 kg, savolitinib will be given at a daily dose of 400 mg.
Treatment cycles are comprised of 21 days, and treatment will continue until progressive disease, unacceptable toxicity, death, or other termination criteria are met—whatever happens first.
The primary end point of the trial is objective response rate by independent review committee assessment and RECIST v1.1 criteria. Key secondary end points include progression-free survival by RECIST v1.1 criteria and safety.
The study is anticipated to enroll about 60 patients,1 with an estimated primary completion date of April 2025.2
A previous analysis published in JCO Precision Oncology showed that the use of circulating tumor DNA via baseline tumor tissue or rebiopsy resulted in the identification of several MET mutations previously unidentified upon progression on savolitinib in patients with gastric cancer, as well as MET amplifications as drivers of resistance to the agent during monotherapy treatment of those with MET-amplified disease.3
Utilizing a next-generation sequencing 100-gene panel, investigators revealed the following target mechanisms of resistance MET D1228V/N/H and Y1230C mutations or high copy number MET gene amplifications that occur when a patient with MET-amplified gastric cancer develops resistance to savolitinib.
Savolitinib is approved in China for patients with non–small cell lung cancer harboring MET exon 14 skipping alterations whose disease has progressed after previous systemic treatment or are not able to receive chemotherapy.1 The agent is being explored as a monotherapy and in combination with other agents in several tumor types like lung, kidney, and gastric cancers.