Furmonertinib Combined With Anlotinib as the First-line Treatment in Patients With EGFR Mutation-positive NSCLC

NCT ID: NCT04895930

Last Updated: 2023-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-12
• Study Completion Date: 2023-11-30

Brief Summary

The aim of this phase Ⅱ study is to evaluate the efficacy and safety of Furmonertinib combined with Anlotinib as the first-line treatment in locally advanced or metastatic non-small cell lung cancer with sensitive EGFR mutations.

Conditions

Non-Small-Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Furmonertinib Plus Anlotinib

Furmonertinib (80mg) plus Anlotinib (10mg)

Group Type: EXPERIMENTAL

Furmonertinib

Intervention Type: DRUG

80mg/day orally on a continuous dosing schedule. If subjects suffer from AEs, they can get declined dosage (40mg).

Anlotinib

Intervention Type: DRUG

10mg/day orally from day 1 to 14 of a 21-day cycle. If subjects suffer from AEs, they can get declined dosage (8mg).

Interventions

Furmonertinib

80mg/day orally on a continuous dosing schedule. If subjects suffer from AEs, they can get declined dosage (40mg).

Intervention Type: DRUG

Anlotinib

10mg/day orally from day 1 to 14 of a 21-day cycle. If subjects suffer from AEs, they can get declined dosage (8mg).

Intervention Type: DRUG

Other Intervention Names

AST2818

Eligibility Criteria

Inclusion Criteria

1. Subjects have voluntarily participated, signed and dated informed consent;

2. Male or female subjects aged ≥18 and ≤75 years old;

3. Locally advanced or metastatic adenocarcinoma NSCLC confirmed by histology or cytology (according to the 8th Edition of the AJCC Staging system), not suitable for surgery or radiotherapy;

4. ECOG score 0-1, and life expectancy no less than 12 weeks according to the investigator's assessment;

5. The tumour harbours one of the most common EGFR mutations (19del or L858R) ;

6. According to RECIST 1.1, subjects have at least one measurable tumor lesion at baseline, and had not received radiotherapy previously;

7. No previous systemic anti-tumor therapy for locally advanced or metastatic NSCLC. For recurrent disease, adjuvant therapy or neoadjuvant therapy may be accepted, but recurrence occurs ≥6 months from stopping treatment;

8. Subjects with stable clinical symptoms of pleural effusion or ascites after symptomatic treatment;

9. For premenopausal women with fertility, the result of serum or urine pregnancy test should be negative within 7 days before the first dose.

Exclusion Criteria

1. Not lung adenocarcinoma, including lung squamous carcinoma, or mixed histology, etc;

2. Subjects are expected to participate in other clinical studies during this trial period;

3. Imaging evidence showed that the tumor had invaded critical blood vessels;

4. Subjects who receive systemic anti-tumor therapy used for locally advanced or metastatic NSCLC previously;

5. With other malignant tumors at present or history of other malignant tumors within 5 years;

6. Leptomeningeal metastases or central nervous system metastasis requiring emergency treatment;

7. At the beginning of study treatment, any unresolved toxic reaction to prior treatment (e.g., adjuvant chemotherapy) exceeds CTCAE Grade 1;

8. History of ILD, drug-induced ILD, radiation pneumonitis which require steroid treatment, or with suspected clinical manifestations of ILD or high risk factors;

9. Severe gastrointestinal dysfunction may affect the intake, transport or absorption of the study drugs;

10. Recent active digestive diseases or other conditions that may cause gastrointestinal bleeding or perforation;

11. Presence of bleeding constitution or active bleeding; any bleeding event ≥CTCAE grade 3, unhealed wounds, ulcers, or fractures occurred within 28 days prior to the first dose;

12. Any of the following organ function criteria is met (no blood or blood product transfusions, no hematopoietic stimulating factors, no albumin or blood product transfusions within 7 days prior to examination): Absolute value of neutrophil (NE)<1.5 × 109/L, platelet (PLT) count<90 × 109/L, hemoglobin (HGB)<90 g/L; Serum total bilirubin (TBIL)>1.5 × ULN, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>2.5 × ULN (for liver metastases or Gilbert Syndrome, TBIL>3 × ULN, and AST and/or ALT>5 × ULN); Serum creatinine (SCr)>1.5 × ULN, or creatinine clearance<60ml/min. (According to the Cockcroft and Gault formula); Urinary protein ≥ ++, or 24-hour urine protein>1.0g; International normalized ratio（INR）>1.5 and activated partial thromboplastin time (APTT)>1.5 ULN; Fasting blood glucose >10mmol/L；

13. Any of the following cardiac criteria is met：

• At rest, the mean corrected QT interval (QTc) by ECG > 470 msec；
• Seriously abnormal of heart rhythm, conduction, or morphology of resting ECG;
• Any factors that may increase the risk of prolonged QTc or risk of arrhythmic events;
• Left ventricular ejection fraction (LVEF) < 50%;
• Uncontrollable hypertension (systolic blood pressure≥150 mmHg and/or diastolic blood pressure≥100 mmHg);

14. With active infection diseases, such as HBV, HCV and HIV;

15. Known or suspected to be allergic to Furmonertinib and Anlotinib and / or other components of their preparations;

16. Pregnancy or lactation;

17. Subjects who are considered ineligible for the study for other reasons according to the investigator's assessment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allist Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Baohui Han

Director of department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Baohui Han, MD

Role: CONTACT

xkyyhan@gmail.com

+86 021-22200000

Facility Contacts

Baohui Han

Role: primary

References

Shi Y, Hu X, Zhang S, Lv D, Wu L, Yu Q, Zhang Y, Liu L, Wang X, Cheng Y, Ma Z, Niu H, Wang D, Feng J, Huang C, Liu C, Zhao H, Li J, Zhang X, Jiang Y, Gu C. Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study. Lancet Respir Med. 2021 Aug;9(8):829-839. doi: 10.1016/S2213-2600(20)30455-0. Epub 2021 Mar 26.

Reference Type: BACKGROUND

PMID: 33780662 (View on PubMed)

Other Identifiers

AST-PMR2002

Identifier Type: -

Identifier Source: org_study_id