Study of Anlotinib Combined With Osimertinib as Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M

NCT04029350 | Unknown Phase 2

• 1 other identifier: ALTN-03-II-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 4

Brief Summary

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

  each 42 days up to PD or death (up to 24 months)

Secondary Outcomes (4)

• OS（Overall Survival）

  up to 24 months

• ORR（Objective Response Rate）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• DCR（Disease Control Rate）

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

• Adverse Events

  Until 30 day safety follow-up visit

Study Arms (1)

Anlotinib Combined With Osimertinib

EXPERIMENTAL

Anlotinib 12 mg once a day from day 1 to 14 of a 21-day cycle. Osimertinib 80mg p.o, qd. It should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.

Drug: Anlotinib Combined With Osimertinib

Interventions

Anlotinib Combined With Osimertinib DRUG

Anlotinib：12mg/capsule, take once when limosis in the morning. If patients suffer from AEs, they can get declined dosage (10mg or 8mg). Osimertinib：80 mg/tablet， per os (p.o.) daily. It should be continued until disease progression or intolerable toxicity or patients withdraw of consent.

Also known as: A+T

Anlotinib Combined With Osimertinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC (according to the 8th Edition of the AJCC Staging system).
• Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing.
• Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent first- or second-generation EGFR TK treatment regimen.
• years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1).
• ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be \<25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment.
• Main organs function is normal.
• Signed and dated informed consent.
• The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.

You may not qualify if:

• Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
• Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation.
• Prior treatment with a third-generation EGFR TKI (i.e. Rociletinib, Olmutinib、BPI-15086、BPI-7711、Osimertinib); Prior treatment with agents targeting the VEGF pathway, including bevacizumab and Anlotinib.
• Treatment with an EGFR TKI (i.e. erlotinib, gefitinib or afatinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment；Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within five half-lives of the compound or 3 months, whichever is greater
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 platinum-therapy related neuropathy
• Any factor that would preclude adequate absorption of Osimertinib and Anlotinib, including refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection
• Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 28 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
• Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or receiving the Mitomycin C 6 weeks prior to medication). Extra-field radiotherapy (EF-RT) was performed 4 weeks prior to allocation or restricted radiotherapy for assessing tumor lesions within 2 weeks prior to allocation
• Patients with any severe and/or uncontrolled disease, including:
• Inadequately controlled hypertension (HTN) (systolic blood pressure \[SBP\] \> 140 mmHg and/or diastolic blood pressure \[DBP\] \> 90 mmHg despite antihypertensive medication)
• Mean resting corrected QT interval (Fridericia's correction formula \[QTcF\]) \> 470 ms ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block); Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval;
• Active or uncontrollable serious infection (≥CTC AE Level 2 infection)
• Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need to be treated with antiretroviral therapy
• Poor control of diabetes (fasting blood glucose \[FBG\]\> 10 mmol/L)
• Urine routine test protein ≥++, and confirmed 24 hours urine protein\> 1.0 g

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (4)

Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Location

Hebei Provincial People's Hospital

Shijiazhuang, Hebei, China

Location

Shanxi Provincal Cancer Hospital

Taiyuan, Shanxi, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Related Publications (6)

• Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

  PMID: 27959700 BACKGROUND

• Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039.

  PMID: 30098152 BACKGROUND

• Akamatsu H, Teraoka S, Morita S, Katakami N, Tachihara M, Daga H, Yamamoto N, Nakagawa K. Phase I/II Study of Osimertinib With Bevacizumab in EGFR-mutated, T790M-positive Patients With Progressed EGFR-TKIs: West Japan Oncology Group 8715L (WJOG8715L). Clin Lung Cancer. 2019 Jul;20(4):e492-e494. doi: 10.1016/j.cllc.2019.03.002. Epub 2019 Mar 19.

  PMID: 31085043 RESULT

• Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. doi: 10.1016/S1470-2045(19)30035-X. Epub 2019 Apr 8.

  PMID: 30975627 RESULT

• Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.

  PMID: 25175099 RESULT

• Wang X, Li Z, Wang L, Liang Y, Huang C, Chen P, Huang D, Song X, Ding C, Wang C, Jiang R. Osimertinib plus anlotinib for advanced NSCLC with acquired EGFR T790M mutation: results from a multicenter phase II study with ctDNA analysis. BMC Med. 2025 Apr 15;23(1):223. doi: 10.1186/s12916-025-04044-8.

  PMID: 40234867 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Richeng Jiang, Doctor

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2019
• First Posted: July 23, 2019
• Study Start: July 31, 2019
• Primary Completion: January 31, 2020
• Study Completion: November 30, 2021
• Last Updated: August 21, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 6 months of study completion
• Access Criteria: Data access requests will be reviewed by an external indepentent Review Panel. Requestors will be required to sign a Data Access Agreement.

Locations

CN (4)