Combining Dacomitinib and Anlotinib for Advanced Lung Cancer Treatment

An Open Label, Multicenter, Phase I/IIB Study of Dacomitinib Plus Anlotinib for Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) 21-L858R Mutations.

This study is testing if combining two drugs, dacomitinib and anlotinib, can help people with advanced lung cancer that has a specific mutation feel better and improve their treatment results.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Chest Hospital (Academic / other)
• Drugs / interventions: dacomitinib, anlotinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05271916 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label study investigates the safety and efficacy of dacomitinib combined with anlotinib as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR 21-L858R mutations. The study consists of two parts: a Phase I dose escalation to determine the optimal dosage and a Phase IIB randomized controlled trial to assess treatment outcomes. Participants will be monitored for response rates and safety profiles throughout the study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable, advanced NSCLC and confirmed EGFR 21-L858R mutations.

Not a fit: Patients with prior systemic therapy for advanced NSCLC or those with other EGFR mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new effective option for patients with advanced NSCLC with specific genetic mutations.

How similar studies have performed: While this approach is novel in combining these specific agents for this mutation, similar studies have shown promise in targeting EGFR mutations in lung cancer.

Eligibility criteria

Inclusion Criteria:

1. ≥18 years of age and ≤75 years;
2. Provision of a voluntarily given, personally signed and dated, written informed consent document;
3. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
4. It is acceptable for subjects with the presence of EGFR activating mutation (exon 19 deletion and the L858R mutation in exon 21) to be included in this Phase I study; Only subjects with the L858R mutation in exon 21 to be included in this Phase IIb;
5. At least one measurable disease by RECIST criteria version 1.1;
6. Patients with controlled or stable brain metastases;
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
8. No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
9. Able to comply with required protocol procedures and able to receive oral medications;
10. Adequate organ function, including:

(1) Adequate bone marrow function Hemoglobin≥90g/L, absolute neutrophil count (ANC) should be ≥ 1.5x109/L, platelets should be ≥ 80x109/L; (2) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN), Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Creatinine≤ 1.5 x upper normal limit (ULN), or ≥ 60 mL/min; (3) Cardiac function: LVEF≥50% assessed by Doppler ultrasound；

Exclusion Criteria:

1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
2. Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
3. Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
4. Patients with pre-existing meningeal metastases;
5. Patients who have concurrent other malignant tumors;
6. Any history of hemoptysis, hematochezia, bloody sputum;
7. Tumor invasion or adjacent major vessels;
8. Patients with uncontrolled or significant systematic disease, including: active infection, thyroid dysfunction, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, or myocardial infarction within 6 months, or severe arrhythmia requiring medication;
9. A history of other diseases, or metabolic dysfunction, or physical examination or laboratory results suggestive of a disease or condition that precludes the use of an investigational drug, or may affect the interpretation of the study results, or expose the patient to a high risk of treatment complications;
10. Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;
11. Pregnant or lactating females;
12. Patients allergic to any pharmaceutical ingredient.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Bo Zhang, MD

Conditions Non-Small Cell Lung Cancer