D-0316 Versus Icotinib in Patients With Locally Advanced or Metastatic EGFR Sensitising Mutation Positive NSCLC

NCT04206072 | Completed Phase 2 DMC

• 1 other identifier: IBIO-103
• Study Type: interventional
• Target: 362
• Locations: 1 country
• Sites: 2

Brief Summary

To assess the efficacy and safety of D-0316 versus Icotinib, a standard of care epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in patients with locally advanced or Metastatic Non Small Cell Lung Cancer (NSCLC).

Conditions

Non-Small Cell Lung Cancer; EGFR Gene Mutation

Keywords

D-0316; EGFR mutated NSCLC

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS) assessed by IRC

  PFS is defined as the time from randomization until the date of objective disease progression or death by any cause, whichever occurs first. The primary endpoint of PFS was based on independent review committee (IRC) assessment.

  From randomization to objective disease progression or death, whichever came first, assessed up to 20 months

Secondary Outcomes (8)

• Median Progression Free Survival (PFS) assessed by Investigator

  From randomization to objective disease progression or death, whichever came first, assessed up to 20 months

• Objective Response Rate (ORR)

  At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months

• Duration of Response (DoR)

  At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months

• Disease Control Rate (DCR)

  At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months

• Overall Survival (OS)

  From randomization to date of death from any cause, whichever came first, up to 36 months

Other Outcomes (1)

• Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire

  At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months

Study Arms (2)

D-0316

EXPERIMENTAL

D-0316 (75 mg or 100 mg orally, once daily), in accordance with the randomization schedule.

Drug: D-0316 Capsule

Icotinib

ACTIVE COMPARATOR

Icotinib (125 mg orally, three times daily), in accordance with the randomization schedule.

Drug: Icotinib Hydrochloride Tablets

Interventions

D-0316 Capsule DRUG

The initial dose of D-0316 is 75 mg orally once daily (QD) for one cycle, and then increased to 100 mg orally QD in the absence of CTCAE grade ≥ 2 headache or thrombocytopenia during the first cycle, otherwise maintained to 75 mg orally QD until disease progression or meet the discontinuation criteria. A cycle of treatment is defined as 21 days of once daily treatment. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were confirmed T790M mutation positive may have the option to continuously receive D-0316.

D-0316

Icotinib Hydrochloride Tablets DRUG

Icotinib (125 mg three times daily, orally), treatment should continue until disease progression or meet the withdrawal criteria. A cycle of treatment is defined as 21 days of three times daily treatment. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Icotinib arm and confirmed T790M mutation positive have the option to receive D-0316 (crossover to active D-0316).

Also known as: Conmana

Icotinib

Eligibility Criteria

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

You may qualify if:

• Male or female, 18 years of age or older.
• Pathologically confirmed adenocarcinoma of the lung, with locally advanced or metastatic disease and not amenable to curative surgery or radiotherapy (stage IIIB, IIIC or IV disease based on the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification). Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
• Patients must be treatment-naive for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with icotinib. Prior adjuvant and neo-adjuvant therapy (except for EGFR-TKI) is permitted if have been completed at least 6 months prior to initiation of study drug.
• The tumour tissues harbour one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by central laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Predicted survival ≥ 3 months
• At least 1 measurable tumor lesion as per RECIST v1.1
• Agree to use effective contraception during the study period and for at least 3 months after completion of the study treatment
• Provision of informed consent prior to any study procedure.

You may not qualify if:

• Evidence of any concurrent or history of malignancy (except for clinically cured in situ cervix carcinoma, basal cell or squamous epithelial skin cancer, thyroid papillary carcinoma).
• Prior treatment with EGFR-TKI.
• Prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC including chemotherapy, biological therapy, immunotherapy, and etc.
• Previous therapeutic clinical trial with 4 week of the first dose of study drug.
• Previous traditional chinese medicine with an anti-cancer indication within 2 weeks of the first dose of study drug.
• Previous major surgery (except for tooth extraction) within 4 weeks of the first dose of study drug, planing to have major surgery during study.
• Symptoms or signs worsened within 2 weeks before screening.
• Any unresolved toxicities from prior treatment greater than NCI CTCAE v4.03 grade 2 or higher, with the exception of hair loss.
• Spinal cord compression, symptomatic or unstable central nervous system (CNS) metastases that require the use of steroids. Patients who have a stable CNS status for at least 4 weeks before treatment will be allowed to join the study.
• Any evidence of serious or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding diatheses, or active infection including hepatitis B, hepatitis C, syphilis and human immunodeficiency virus (HIV).
• Clinically significant cardiovascular disease, such as mean resting corrected QT interval (QTcF) ≥470 msec (female) or ≥450 msec (male), obtained from 3 ECGs, or any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG or left ventricular ejection fraction (LVEF) ≤ 50%, etc.
• Previous history of interstitial lung disease, drug-induced interstitial lung disease, history of radiation-induced pneumonia requiring hormone therapy, or clinical evidence of active interstitial lung disease.
• Presence of active gastrointestinal disease or other condition that would preclude the absorption, distribution, metabolism, or excretion of study drug.
• Patients currently receiving medications known to be potent inducers, sensitive substrate or potent inhibitor of cytochrome P450 (CYP) 3A4 (e.g. CYP3A4), CYP3A5, CYP2D6 and CYP2C8.
• Patients with a known allergy or delayed hypersensitivity reaction to study drug or its excipient.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (2)

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, Zhejiang, China

Location

Liuzhou Workers Hospital

Liuchow, China

Location

Related Publications (2)

• Lu S, Zhou J, Jian H, Wu L, Cheng Y, Fan Y, Fang J, Chen G, Zhang Z, Lv D, Jiang L, Wu R, Jin X, Zhang X, Zhang J, Xie C, Sun G, Huang D, Cui J, Guo R, Han Z, Chen Z, Liang J, Zhuang W, Hu X, Zang A, Zhang Y, Cang S, Lan Y, Chen X, Liu L, Li X, Chen J, Ma R, Guo Y, Sun P, Tian P, Pan Y, Liu Z, Cao P, Ding L, Wang Y, Yuan X, Wu P. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respir Med. 2023 Oct;11(10):905-915. doi: 10.1016/S2213-2600(23)00183-2. Epub 2023 May 24.

  PMID: 37244266 DERIVED

• Lu S, Zhang Y, Zhang G, Zhou J, Cang S, Cheng Y, Wu G, Cao P, Lv D, Jian H, Chen C, Jin X, Tian P, Wang K, Jiang G, Chen G, Chen Q, Zhao H, Ding C, Guo R, Sun G, Wang B, Jiang L, Liu Z, Fang J, Yang J, Zhuang W, Liu Y, Zhang J, Pan Y, Chen J, Yu Q, Zhao M, Cui J, Li D, Yi T, Yu Z, Yang Y, Zhang Y, Zhi X, Huang Y, Wu R, Chen L, Zang A, Cao L, Li Q, Li X, Song Y, Wang D, Zhang S, Ding L, Zhang L, Yuan X, Yao L, Shen Z. Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter, Single-Arm, Open-Label Study. J Thorac Oncol. 2022 Oct;17(10):1192-1204. doi: 10.1016/j.jtho.2022.06.002. Epub 2022 Jun 18.

  PMID: 35724798 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

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

• Shun Lu, PHD

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 20, 2019
• Study Start: December 24, 2019
• Primary Completion: July 30, 2022
• Study Completion: July 15, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

CN (2)