Furmonertinib treatment for advanced lung cancer with uncleared ctDNA

FurmOnertinib Mesylate With or Without Chemotherapy +/- bevacizUmab as firSt Line Treatment in Advanced Non-small Cell Lung Cancer Patients With Uncleared Epidermal Growth Factor Receptor (EGFR) Mutation Positive Circulating Tumor Cell DNA

This study is testing if a new lung cancer drug called furmonertinib works better alone or with other treatments for patients whose cancer has certain markers in their blood.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 280 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, furmonertinib, bevacizumab
• Locations: 26 sites (Changchun and 25 other locations)
• Trial ID: NCT05334277 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of furmonertinib monotherapy compared to combination therapy in patients with advanced non-small cell lung cancer (NSCLC) who have uncleared circulating tumor DNA (ctDNA). The study will enroll approximately 280 patients, randomly assigning them to receive either furmonertinib alone or in combination with chemotherapy or chemotherapy plus bevacizumab. The trial includes a screening period, treatment period, and follow-up, with patients expected to attend around nine visits for assessments. The goal is to determine the best treatment approach for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with untreated advanced non-squamous NSCLC and specific EGFR mutations.

Not a fit: Patients with squamous cell lung cancer or those who have previously received treatment for their advanced NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced EGFR mutant NSCLC who have uncleared ctDNA.

How similar studies have performed: While this approach is novel in the context of uncleared ctDNA, other studies have shown promise with similar therapies in advanced NSCLC.

Eligibility criteria

Inclusion Criteria:

1. Provide informed consent prior to any study specific procedures;
2. at least 18 years of age;
3. ECOG PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks, life expectancy ≥12 weeks;
4. Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC);
5. Locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy;
6. Patient with EGFR 19Del or L858R mutation diagnosed histologically or cytologically and confirmed by ctDNA, the reports must be issued or recognized by Tier 3A hospitals. The mutations above may exist alone or together;
7. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy;
8. According to RECIST 1.1, patients have at least one tumor lesion at baseline that meets the following requirements: accurately and repeatably measurable at baseline;
9. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the first dose, and the pregnancy test (blood or urine test) must be negative; female subjects must not be lactating;
10. Willing to use contraception as appropriate during the study and for a period after discontinuing study treatment;
11. Voluntary and agree to follow the study treatment protocol as well as follow-up plan, and can accept the oral medicine treatment;
12. Voluntary and agree to sign the informed consent for genetic research, and provide enough fresh blood samples for central NGS testing.

Exclusion Criteria:

1. squamous cell lung carcinoma;
2. History of hypersensitivity to active or inactive excipients of investigational product (IP) or drugs with a similar chemical structure or class to investigational product (IP);
3. Confirmed EGFR 20 exon insertion mutations at any time after the initial diagnosis;
4. Patient who receive prior treatment including any of the following:

   * Any Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI);
   * The patients who have received intrapleural perfusion therapy can only be enrolled 28 days or more after the pleural effusion is stable;
   * Major surgery within 4 weeks of the first dose of investigational product (IP);
   * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP;
   * CYP3A4 strong inhibitor or strong inducer is used within 7 days prior to the first dose, or need to receive these drugs during the study period;
   * Traditional Chinese medicine and traditional Chinese medicine preparations with anti-tumor as indications and with adjuvant treatment of tumor is used within 7 days prior to the first dose, or need to receive these drugs during the study period;
   * Patients who are receiving drugs known to prolong QTc interval or may cause torsade de pointe and need to continue to receive these drugs during the study period;
   * The time from the treatment with any other investigational product or its analogue to the first dose does not exceed 5 half-lives of the drug or 14 days, whichever is longer;
5. Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiation including chemotherapy, biologic therapy, target therapy, immunotherapy, or any investigational drug, except neoadjuvant or adjuvant therapy before 6 months prior to the first dose;
6. At the beginning of study treatment, any unresolved toxic reaction to prior treatment is present, which exceeds Grade 1 in accordance with Common Terminology Criteria for Adverse Events (CTCAE) (except for alopecia), and exceeds Grade 2 for prior platinum treatment-related neuropathy.
7. Spinal cord compression; symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids.
8. Diagnosed other malignant tumors or had a history of other malignant tumors in last 5 years, except for skin basal cell carcinoma, cervical carcinoma in situ and breast ductal carcinoma in situ which have been effectively controlled;
9. Recent active digestive diseases such as duodenal ulcer, ulcerative colitis, ileitis, intestinal perforation, intestinal fistula, or other conditions that may cause gastrointestinal bleeding or perforation as the researchers may prescribe. Or refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of IP;
10. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, and active infection, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial;
11. Past medical history of Interstitial Lung Disease (ILD), drug-induced Interstitial Lung Disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active Interstitial Lung Disease;
12. Any evidence of known corneal injury;
13. Inadequate bone marrow reserve or organ function;
14. QT prolongation or any clinically important abnormalities in rhythm or heart function;
15. Patients who may have poor compliance with the research procedures and requirements, etc., as judged by investigators;
16. Pregnancy or lactation;
17. Patients who have had allogeneic bone marrow transplantation or received blood transfusion within 120 days prior to genetic sample collection.

Where this trial is running

Changchun and 25 other locations

• The First Hospital of Jilin University — Changchun, China (Not_yet_recruiting)
• Sichuan Provincial People's Hospital — Chengdu, China (Not_yet_recruiting)
• Dongguan People's Hospital — Dongguan, China (Not_yet_recruiting)
• Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang People's hospital — Dongyang, China (Not_yet_recruiting)
• The First People's Hospital of Foshan — Foshan, China (Not_yet_recruiting)
• Affiliated Cancer Hospital and Institute of Guangzhou Medical University — Guangzhou, China (Not_yet_recruiting)
• Nanfang Hospital, Southern Medical University — Guangzhou, China (Not_yet_recruiting)
• Sun Yat-sen University cancer center — Guangzhou, China (Recruiting)
• The First Affiliated Hospital, Sun Yat-sen University — Guangzhou, China (Not_yet_recruiting)
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, China (Not_yet_recruiting)
• The Second Affiliated Hospital Zhejiang University School of Medicine — Hangzhou, China (Not_yet_recruiting)
• Zhejiang Provincial Hospital of Chinese Medicine — Hangzhou, China (Not_yet_recruiting)
• Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University — Jiangmen, China (Not_yet_recruiting)
• Affiliated Jinhua Hospital, Zhejiang University School of Medicine — Jinhua, China (Not_yet_recruiting)
• Mianyang Central Hospital — Mianyang, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, China (Not_yet_recruiting)
• Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute — Shenyang, China (Not_yet_recruiting)
• Shijiazhuang People's hospital — Shijiazhuang, China (Not_yet_recruiting)
• The Affiliated Cancer Hospital of Xinjiang Medical University — Ürümqi, China (Not_yet_recruiting)
• The Third Affiliated Hospital of Wenzhou Medical University, Rui'an People's Hospital — Wenzhou, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, China (Not_yet_recruiting)
• Yijishan Hospital, Wannan Medical College — Wuhu, China (Not_yet_recruiting)
• Tangdu Hospital, Fourth Military Medical University — Xi'an, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an, China (Not_yet_recruiting)
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Zhang MD Li, 58

Conditions Non-small Cell Lung Cancer; Non-Small Cell Lung Cancer