Orpathys (savolitinib)

P3, N=147, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=220 --> 147

P2, N=120, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.

P2, N=200, Not yet recruiting, Peking University Shenzhen Hospital

P2, N=69, Completed, Queen Mary University of London | Active, not recruiting --> Completed | N=181 --> 69 | Trial completion date: Mar 2023 --> Jul 2024 | Trial primary completion date: Mar 2023 --> Jul 2024

P2, N=47, Active, not recruiting, AstraZeneca | Suspended --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025

After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Postoperative tepotinib continued, with no relapse at 6-month follow-up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping-mutated NSCLC, warranting further clinical trials.

P2, N=25, Recruiting, Jeeyun Lee | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC.

No abstract available

Despite maintaining a prolonged progression-free survival (PFS) with first-generation EGFR-TKI Afatinib, disease progression occurred in 2022 without detectable resistance mutations. Transition to second-generation TKI Furmonertinib resulted in poor control, with rapid progression including unusual bilateral breast metastases that exhibited inflammatory breast cancer-like peau d'orange changes...This case underscores the importance of continuous genetic profiling and tailored treatment approaches in managing advanced lung adenocarcinoma, particularly when presenting with rare metastatic sites and complex genetic landscapes. The successful application of Savolitinib following the identification of a MET amplification mutation highlights its potential in overcoming resistance mechanisms in NSCLC, providing a significant therapeutic option for similarly challenging cases.

The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts.

P2, N=120, Not yet recruiting, Sun Yat-sen University

To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual.

P3, N=220, Recruiting, AstraZeneca | Trial completion date: Sep 2026 --> Jun 2026

One patient has concomitant BRAF V600E mutation, and another patient had savolitinib as first line of therapy but discontinued due to hepatotoxicity. Our experience showed in real clinical setting, tepotinib had robust and durable clinical activity and a favorable toxicity profile in Chinese patients with METex14 skipping NSCLC. It is the first report on the effectiveness of tepotinib in a patient with both METex14 skipping and BRAF V600E mutations and successful MET inhibitor switch after MET inhibitor-induced liver injury.

P1, N=7, Completed, AstraZeneca | Recruiting --> Completed

No abstract available

H-FLAC harboring MET amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with MET amplification.

P2, N=366, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression...DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.

Targeting MET with savolitinib and capmatinib efficiently suppressed the growth of MET-amplified GC cells. Moreover, these MET inhibitors exerted synergistic effects with trastuzumab on HER2- and MET-amplified GC cells.

Drug sensitivity analysis showed that the low-risk group was more sensitive to Erlotinib, Savolitinib and VE _ 822, which may be used as a potential drug for COAD treatment. This study constructed and verified a TLS model that can predict COAD. More importantly, it provides a reference standard for guiding the prognosis and immunotherapy of COAD patients.

The drug-sensitivity results showed that patients in the high-risk group were more sensitive to treatment with crizotinib, erlotinib or savolitinib. Finally, the expression levels of AL157895.1 were found to be lower in A549. In summary, a novel DR-lncRNA signature was constructed, which provided a new index to predict the efficacy of therapeutic interventions and the prognosis of patients with LUAD.

P2, N=6000, Recruiting, Hunan Province Tumor Hospital | Phase classification: P --> P2 | N=100 --> 6000 | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=120, Recruiting, Hunan Province Tumor Hospital | Phase classification: P --> P2

P=N/A, N=120, Recruiting, Hunan Province Tumor Hospital | N=80 --> 120 | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

P1, N=8, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

P2, N=152, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Dec 2024 | Trial primary completion date: Oct 2020 --> Oct 2023

Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

No abstract available

P1, N=8, Not yet recruiting, AstraZeneca

P1, N=344, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024

P2, N=60, Suspended, AstraZeneca | Recruiting --> Suspended

P2, N=200, Active, not recruiting, Canadian Cancer Trials Group | Recruiting --> Active, not recruiting | N=600 --> 200

P2, N=248, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2025 --> May 2025 | Trial primary completion date: Nov 2025 --> May 2025

P2, N=600, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=44, Active, not recruiting, Guangdong Association of Clinical Trials | Recruiting --> Active, not recruiting

Our results suggest osimertinib and savolitinib combination is most effective for osimertinib resistant EGFR-mutant tumors with MET pathway activation as evidenced by phospho-MET. As subclonal MET amplification may be evident in MET polysomy tumor progression, MET polysomy warrants close clinical follow up with phospho-MET IHC in parallel with FISH diagnostic.

Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines...Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.

P3, N=60, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024