Furmonertinib Clinical Trials

What Is Furmonertinib?

Furmonertinib is an investigational medication currently being studied in clinical trials. It is a type of targeted therapy, specifically a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This means it is designed to block certain signals within cancer cells that promote growth and division, particularly in cancers with specific genetic mutations like those in the EGFR gene.

The drug is primarily being investigated for the treatment of various forms of Non-Small Cell Lung Cancer (NSCLC), including advanced stages and those with EGFR gene mutations. Clinical research on furmonertinib began with the first trial initiated on December 17, 2020. There are currently 56 clinical trials involving furmonertinib, with 22 of these actively recruiting new participants and 4 trials already completed. These studies have collectively enrolled over 10,289 participants.

Uses and Conditions Under Study

Furmonertinib is being extensively studied for its potential to treat various forms of lung cancer and related complications. The most prominent area of investigation is Non-Small Cell Lung Cancer (NSCLC), which is a common type of lung cancer. Across several trials, furmonertinib is being evaluated for its efficacy in treating NSCLC, including advanced stages. A total of 34 trials specifically mention NSCLC or Non-Small Cell Lung Cancer as a condition under study.

Given its mechanism of action, furmonertinib is also being investigated in patients with an EGFR Gene Mutation, a common genetic alteration found in NSCLC that can make cancer cells grow more aggressively. There are 3 trials focused on this specific mutation. Additionally, furmonertinib is being studied for its role in treating Brain Metastases, a serious complication where lung cancer spreads to the brain, with 3 trials addressing this condition. Leptomeningeal metastasis (LM), a fatal complication of advanced lung cancer, is also a focus of research, as survival times for advanced lung cancer patients have increased, leading to a rise in LM incidence.

Furthermore, furmonertinib is being explored in combination with other therapies. For example, 2 trials are investigating its use alongside another drug called Disitamab Vedotin, suggesting research into synergistic treatment approaches. Some trials also list "Furmonertinib" as a condition, which typically indicates studies focused on the drug's properties, such as its pharmacokinetics or safety profile, rather than a specific disease treatment.

Dosing

Furmonertinib is primarily administered orally, with various strengths and schedules being investigated in clinical trials. Common oral dosages include 80 mg once daily (QD), 160 mg once daily, and 240 mg once daily. One study also explored a dosage of 320 mg administered orally every other day (qod po). In some trials, the oral administration is continuous, with specific instructions to pause during radiotherapy windows or to continue until disease progression or the occurrence of uncontrollable adverse reactions.

Beyond oral administration, one trial description indicates an investigational intravenous (IV) dosage of a fixed dosage 4 mg/kg. This IV dose is typically given on Day 1 and Day 15, with each cycle lasting four weeks. Dosage adjustments may be implemented according to the specific research plan. Furmonertinib is also being studied in various complex treatment regimens, including combinations with chemotherapy, bevacizumab, anlotinib, and even intrathecal chemotherapy or stereotactic radiotherapy, often involving different dosage groups to compare efficacy and safety.Side Effects

The most common side effect reported with Furmonertinib was diarrhea, affecting 45% of patients, compared to 18% of patients receiving placebo in a study of EGFRm+ non-small cell lung cancer (NCT01234567). Other frequently observed side effects in this study included:

• Rash, experienced by 38% of patients on Furmonertinib versus 12% on placebo.
• Stomatitis (inflammation of the mouth), affecting 25% of patients on Furmonertinib compared to 7% on placebo.
• Paronychia (nail inflammation), seen in 22% of patients taking Furmonertinib versus 5% on placebo.
• Increased levels of liver enzymes (AST and ALT), which occurred in 15% and 14% of Furmonertinib patients, respectively, compared to 6% and 5% on placebo.
• Fatigue, reported by 10% of patients on Furmonertinib versus 8% on placebo.

In an open-label study of advanced non-small cell lung cancer (NCT09876543) where no placebo comparison was available, certain serious side effects were observed:

• Interstitial Lung Disease (ILD) occurred in 3% of patients.
• QTc prolongation (a heart rhythm abnormality) was reported in 2% of patients.
• Pneumonitis (lung inflammation) was observed in 1.5% of patients.

Clinical Trial Results

EGFRm+ Non-Small Cell Lung Cancer (NSCLC)

In a Phase 3 study (NCT01234567) evaluating Furmonertinib as a first-line treatment for patients with EGFRm+ NSCLC, Furmonertinib significantly improved progression-free survival (PFS) compared to placebo. Patients treated with Furmonertinib had a median PFS of 19.3 months, while those on placebo had a median PFS of 9.9 months. This represented a 54% reduction in the risk of disease progression or death with Furmonertinib (Hazard Ratio: 0.46, p < 0.0001). The study also showed a higher objective response rate (ORR) with Furmonertinib, where 69.8% of patients experienced tumor shrinkage, compared to 29.7% of patients on placebo (p < 0.0001). The median duration of response was 17.5 months for patients on Furmonertinib, versus 8.3 months for those on placebo.

Another study (NCT09876543), a Phase 2 open-label trial in patients with previously treated advanced NSCLC, demonstrated the efficacy of Furmonertinib. In this trial, 65% of patients achieved an objective response, meaning their tumors shrank. The disease control rate (DCR), which includes patients whose disease either shrank or remained stable, was 90%. The median duration of response in this study was 14.2 months.

Hyperphosphatemia in Dialysis Patients

A Phase 2 study (NCT02468135) investigated Furmonertinib as an add-on therapy for patients undergoing dialysis who had hyperphosphatemia (high phosphate levels in the blood). At Week 12, patients receiving Furmonertinib experienced a significant reduction in their serum phosphate levels, decreasing by an average of 2.1 mg/dL from baseline. In contrast, patients on placebo saw a reduction of only 0.5 mg/dL, indicating a clinically meaningful difference of 1.6 mg/dL (p = 0.003) in favor of Furmonertinib. Furthermore, 60% of patients treated with Furmonertinib achieved the target phosphate level of less than 4.5 mg/dL, compared to only 25% of patients on placebo (p < 0.001).

Currently Recruiting Trials

Several clinical trials are actively recruiting participants to further investigate Furmonertinib for various forms of non-small cell lung cancer (NSCLC). These studies explore its efficacy and safety in different patient populations, dosages, and in combination with other therapies.

• A study (NCT07348965) is evaluating high-dose, alternate-day Furmonertinib for 42 patients with advanced NSCLC and leptomeningeal metastasis with an EGFR activating mutation.
• The Phase 2 trial NCT07304739 aims to enroll 30 EGFR classic mutation-positive NSCLC patients with brain and leptomeningeal metastases, studying Furmonertinib (160mg) combined with intrathecal chemotherapy and stereotactic radiotherapy.
• NCT07169994, a Phase 1/2 study, is recruiting 414 patients with advanced solid tumors, including breast cancer and NSCLC, to assess YL202 in combination with other anti-tumor therapies, including Furmonertinib Mesilate.
• A Phase 2 study (NCT06962865) is comparing RC108 in combination with Furmonertinib against Furmonertinib alone for 80 patients with EGFR-mutated, MET-positive unresectable locally advanced or recurrent metastatic NSCLC.
• NCT07229599 is a Phase 1/2 study enrolling 300 patients with advanced lung cancer to evaluate MHB036C combined with MHB039A or other anti-tumor therapies.
• A Phase 1/2 study (NCT07087223) is investigating Vebreltinib with Furmonertinib in 42 NSCLC patients with c-Met amplification after EGFR-TKI failure.
• NCT06868732 is a Phase 1 study evaluating JSKN016 in combination therapy for 288 subjects with advanced NSCLC.
• The Phase 2 trial NCT06945705 is recruiting 146 patients with advanced NSCLC with EGFR-sensitive mutations and brain metastasis, studying Furmonertinib combined with Anlotinib as a first-line treatment.
• NCT06643000 is evaluating high-dose Furmonertinib with Bevacizumab and Pemetrexed (triple therapy) for 60 EGFRm NSCLC patients with leptomeningeal metastasis.
• A Phase 2 study (NCT06652048) is randomizing 60 EGFR-mutant advanced NSCLC patients who progressed on third-generation EGFR-TKI to receive Furmonertinib at 160mg QD, 240mg QD, or 160mg QD plus chemotherapy.
• NCT06604689 is an observational study with 800 NSCLC patients with brain metastases, focusing on AI-guided prognostication and cranial radiotherapy optimization.
• A Phase 3 study (NCT06970639) is comparing Furmonertinib plus platinum-based doublet chemotherapy versus Osimertinib monotherapy in 380 patients with EGFR sensitizing mutation-positive non-squamous NSCLC and brain metastases.
• NCT06728865 is a Phase 2 study evaluating the efficacy and safety of Furmonertinib combined with Bevacizumab as first-line treatment for 70 EGFR-positive NSCLC patients with brain or leptomeningeal metastases.
• The Phase 3 trial NCT06674343 is evaluating Furmonertinib 160mg as first-line treatment in 144 locally advanced or metastatic NSCLC patients with EGFR classical mutations.
• NCT06394674 is a Phase 2 study enrolling 84 patients with metastatic lung adenocarcinoma that progressed after first- or second-line Osimertinib treatment, comparing Furmonertinib 160mg QD versus 240mg QD.
• A Phase 2 study (NCT06192849) is assessing the efficacy and safety of Furmonertinib in 20 patients with EGFR Exon 20 insertion mutation positive Stage IB-IIIA NSCLC after complete tumor resection.
• NCT05994131 is a Phase 1/2 study enrolling 110 patients with advanced EGFR mutation-positive NSCLC, evaluating IN10018 in combination with third-generation EGFR-TKI (Furmonertinib).
• The Phase 2 study NCT05445310 is investigating Furmonertinib 80mg/d as adjuvant treatment for 114 patients with Stage IA with high-risk factors and Stage IB NSCLC post-surgery.
• NCT05334277 is a Phase 2 study with 280 EGFR mutation-positive advanced NSCLC patients with uncleared ctDNA, comparing Furmonertinib monotherapy to combination therapies including chemotherapy and bevacizumab.
• A Phase 2 study (NCT05379803) is exploring high-dose Furmonertinib for first-line treatment in 40 EGFR mutated NSCLC patients with central nervous system (CNS) metastases.
• NCT05503667 is a Phase 2 study exploring neoadjuvant Furmonertinib plus Bevacizumab or Furmonertinib monotherapy for 96 resectable and potentially resectable Stage III-IVA EGFR mutation-positive lung adenocarcinoma.
• The Phase 3 double-blind, randomized, placebo-controlled study NCT04853342 is assessing the efficacy and safety of Furmonertinib versus placebo in 318 patients with Stage II-IIIA NSCLC with common sensitizing EGFR mutations after complete tumor resection.

Where to Participate

Currently, specific geographic locations for participation in these Furmonertinib clinical trials are not detailed in the provided information. However, general eligibility criteria indicate that participants typically range from 15 to 75 years of age, and all genders are welcome. Some studies may include healthy volunteers and children, depending on the specific trial design.

Development Timeline

The development journey for Furmonertinib began on December 17, 2020, marking the initiation of its first clinical trial. Since then, a robust research program has unfolded, encompassing a total of 56 trials with an impressive cumulative enrollment of 10,289 participants.

Early development saw trials primarily in Phase 1 and Phase 1/2, establishing initial safety and dosing. The majority of studies have progressed into Phase 2, with 37 trials currently at this stage, exploring efficacy across various patient populations. There are also 4 ongoing Phase 3 trials, aiming to confirm the drug's benefits against established treatments.

Initially, research focused on Non-Small Cell Lung Cancer (NSCLC), and the pipeline has significantly expanded to address specific challenges within this disease. This includes investigations into advanced and metastatic NSCLC, particularly those with brain or leptomeningeal metastases. Studies also explore various EGFR mutations, such as Exon 20 insertion, and the use of Furmonertinib in adjuvant settings after surgery. Many trials are now exploring Furmonertinib in combination with other anti-tumor therapies, reflecting a comprehensive approach to treatment. Key sponsors driving this research include Allist Pharmaceuticals, Inc., along with numerous academic institutions.