Savolitinib Clinical Trials

What Is Savolitinib?

Savolitinib is a drug currently under investigation in clinical trials. It is a type of targeted therapy known as a cMET inhibitor. This means savolitinib works by blocking the activity of the cMET protein, which can be overactive in certain types of cancer cells. By inhibiting cMET, savolitinib aims to disrupt cancer cell growth and survival, potentially slowing or stopping tumor growth.

While specific FDA approvals are not detailed in the available data, savolitinib is being studied for its potential to treat various cancers, most notably Non-small Cell Lung Cancer (NSCLC). Clinical research involving savolitinib includes 36 trials with over 10,000 participants, exploring its use both as a single agent and in combination with other therapies, such as osimertinib or durvalumab. These studies aim to evaluate its effectiveness and safety profile across different patient populations and disease stages.

Uses and Conditions Under Study

Savolitinib is primarily being investigated for the treatment of various cancers, with a significant focus on lung cancer. It has been studied in a total of 36 trials involving 10,420 participants since the first trial began in 2014, with the latest trial projected to conclude in 2026.

• Non-small Cell Lung Cancer (NSCLC): This is the most extensively studied condition for savolitinib, with a combined total of 10 trials specifically addressing NSCLC, metastatic NSCLC, and NSCLC with EGFR gene mutations. Savolitinib, as a cMET inhibitor, is being explored for its ability to target specific genetic alterations, particularly those involving the MET pathway, which can drive uncontrolled cell growth in these lung cancers.
• Carcinoma and Solid Tumors: Savolitinib is also being investigated more broadly for carcinoma (3 trials) and solid tumors (2 trials). These studies aim to determine if the drug's mechanism of action, targeting the cMET pathway, can be effective across a wider range of advanced cancers beyond lung cancer. This includes specific research in Colorectal Carcinoma (1 trial).
• Healthy Male Subjects: Two trials have included healthy male subjects. These studies are crucial for understanding the drug's pharmacokinetics – how savolitinib is absorbed, distributed, metabolized, and eliminated by the body – and for assessing its safety profile in individuals without the target disease, before broader patient studies.

Dosing

Savolitinib is primarily administered as an oral medication, likely in the form of tablets or capsules, as indicated by descriptions of "oral daily" and "p.o." (per os, meaning by mouth) administration in clinical trials.

The strengths and dosing schedules of savolitinib have varied across different studies, reflecting its investigational nature:

• Some trials have explored a dose of 300 mg orally once a day, with a cycle typically lasting 28 days.
• Other studies have investigated doses ranging from 400 mg to 600 mg daily. For instance, a dose of 400 mg daily was used for participants weighing less than 60 kg, while 600 mg daily was used for those weighing more than 60 kg. Dose reductions to 400 mg or 200 mg were also permitted based on tolerability.
• In combination regimens, savolitinib has been studied at 300 mg or 200 mg twice daily (BID), with the specific dose determined by safety recommendations.
• Some pharmacokinetic studies have involved a single oral dose of savolitinib to assess its absorption and metabolism.

These varied dosing strategies are part of the ongoing research to identify the most effective and safest dose for different conditions and patient characteristics.

Side Effects

In a clinical trial involving 14 patients taking Savolitinib and 16 patients taking a placebo, the following side effects were reported:

• Nausea was experienced by 50.0% of patients on Savolitinib, compared to 18.8% on placebo.
• Peripheral swelling (oedema peripheral) occurred in 35.7% of patients taking Savolitinib, versus 25.0% on placebo.
• Headache was reported by 28.6% of patients on Savolitinib, while no patients (0.0%) on placebo experienced it.
• Low albumin levels (hypoalbuminaemia) affected 21.4% of patients on Savolitinib, compared to 12.5% on placebo.
• Fatigue was seen in 21.4% of patients on Savolitinib, but no patients (0.0%) on placebo.
• Acne-like rash (dermatitis acneiform) was reported by 21.4% of patients on Savolitinib, and no patients (0.0%) on placebo.
• Vomiting was less common in patients on Savolitinib, affecting 21.4% compared to 31.3% on placebo.
• Low calcium levels (hypocalcaemia) occurred in 14.3% of patients on Savolitinib, while no patients (0.0%) on placebo experienced it.
• Constipation was reported by 14.3% of patients on Savolitinib, versus 6.3% on placebo.
• Joint pain (arthralgia) affected 14.3% of patients on Savolitinib, compared to 6.3% on placebo.

Clinical Trial Results

Kidney Cancer (NCT02761057)

In a study comparing Savolitinib to other treatments for kidney cancer that had progressed, Savolitinib was evaluated alongside Cabozantinib, Crizotinib, and Sunitinib. This trial is registered as NCT02761057.

• The median Overall Survival (OS) for patients receiving Savolitinib was 11.7 months. For comparison, Cabozantinib showed 20.0 months, Crizotinib 19.9 months, and Sunitinib 16.4 months.
• The median Progression-Free Survival (PFS) for Savolitinib was 3.0 months. Other treatments showed: Cabozantinib 9.0 months, Crizotinib 2.8 months, and Sunitinib 5.6 months.
• The Response Rate (RR) for Savolitinib was 3.45%. Cabozantinib had a response rate of 22.73%, Crizotinib 0%, and Sunitinib 4.35%.
• Regarding severe (Grade 3 through 5) adverse events related to the study drugs, 13 participants on Savolitinib experienced such events.

MET-driven Papillary Renal Cell Carcinoma (NCT03091192)

A study compared Savolitinib (once daily) to Sunitinib (once daily) in patients with MET-driven Papillary Renal Cell Carcinoma (PRCC). This trial is registered as NCT03091192.

• The Objective Response Rate (ORR), which measures tumor shrinkage, was 27.3% for patients on Savolitinib, compared to 7.4% for those on Sunitinib.
• The median Progression-Free Survival (PFS) was 7.0 months for Savolitinib, versus 5.6 months for Sunitinib.
• The Disease Control Rate (DCR) at 6 months was 48.5% for Savolitinib, compared to 37.0% for Sunitinib. At 12 months, the DCR was 30.3% for Savolitinib versus 22.2% for Sunitinib.

MET Amplified Metastatic or Unresectable Colorectal Cancer (NCT03592641)

In a study of Savolitinib for patients with MET amplified metastatic or unresectable colorectal cancer, registered as NCT03592641, the median Progression-Free Survival (PFS) was 2.29 months. The Objective Response Rate (ORR) was 0%, meaning no patients experienced tumor shrinkage.

EGFRm+/MET+ NSCLC Following Prior Osimertinib (NCT03778229)

A trial investigated Savolitinib, both as a monotherapy and in combination with Osimertinib, for patients with EGFRm+/MET+ non-small cell lung cancer (NSCLC) who had previously received Osimertinib. This study is registered as NCT03778229.

• The combination of Savolitinib (300 mg twice daily) and Osimertinib showed an Objective Response Rate (ORR) of 58.3%, significantly higher than Savolitinib monotherapy (300 mg twice daily) at 16.0%.
• The median Progression-Free Survival (PFS) for the combination (Savolitinib 300 mg twice daily + Osimertinib) was 8.28 months, compared to 3.65 months for Savolitinib monotherapy.
• The median Duration of Response (DoR) for the combination (Savolitinib 300 mg twice daily + Osimertinib) was 11.76 months, versus 4.53 months for Savolitinib monotherapy.

EGFRm+ and MET Amplified Advanced NSCLC (NCT04606771)

Another study evaluated Savolitinib plus Osimertinib compared to Savolitinib plus placebo in patients with EGFRm+ and MET amplified advanced NSCLC. This trial is registered as NCT04606771.

• The combination of Savolitinib plus Osimertinib resulted in an Objective Response Rate (ORR) of 57.1%, compared to 12.5% for Savolitinib plus placebo.
• Patients receiving Savolitinib plus Osimertinib had a median Progression-Free Survival (PFS) of 7.36 months, while those on Savolitinib plus placebo had a PFS of 1.64 months.
• The median Duration of Response (DoR) was 30.57 weeks for the Savolitinib plus Osimertinib group, whereas it was not available for the Savolitinib plus placebo group.
• Tumor size assessment showed a mean 35.0% reduction in tumor size for the combination therapy, compared to an 8.5% increase for Savolitinib plus placebo.
• The combination therapy also led to a mean 93.6% reduction in EGFR mutation allele frequencies (indicating clearance of mutations), compared to a 62.7% reduction with Savolitinib plus placebo.

Currently Recruiting Trials

Where to Participate

Development Timeline