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

NCT ID: NCT04206072

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 362 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-24
• Study Completion Date: 2025-07-15

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).

Detailed Description

This is a Phase II/III, open-label, randomised study assessing the efficacy and safety of D-0316 (70 mg once daily for 21 days, then increased to 100 mg once daily, orally) versus Icotinib (125 mg three times daily, orally) in patients with locally advanced or metastatic NSCLC that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naive and eligible for first-line treatment with an EGFR-TKI.

Conditions

Non-Small Cell Lung Cancer; EGFR Gene Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

D-0316

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

Group Type: EXPERIMENTAL

D-0316 Capsule

Intervention Type: 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.

Icotinib

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

Group Type: ACTIVE_COMPARATOR

Icotinib Hydrochloride Tablets

Intervention Type: 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).

Interventions

D-0316 Capsule

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.

Intervention Type: DRUG

Icotinib Hydrochloride Tablets

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).

Intervention Type: DRUG

Other Intervention Names

Conmana

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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

Sponsors

Betta Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shun Lu, PHD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital

Locations

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, Zhejiang, China

Liuzhou Workers Hospital

Liuzhou, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 37244266 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35724798 (View on PubMed)

Other Identifiers

IBIO-103

Identifier Type: -

Identifier Source: org_study_id