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

A Phase II/III, Open-Label, Randomised Study to Assess the Safety and Efficacy of D-0316 Versus Icotinib as First Line Treatment in Patients With EGFR Sensitising Mutation, Locally Advanced or Metastatic NSCLC

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).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer; EGFR Gene Mutation
• Intervention / Treatment: Drug: D-0316 Capsule; Drug: Icotinib Hydrochloride Tablets

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.

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Liuzhou, China
    • Liuzhou Workers Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Medical School of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-0316; D-0316 (75 mg or 100 mg orally, once daily), in accordance with the randomization schedule.	Drug: 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.
Active Comparator: Icotinib; Icotinib (125 mg orally, three times daily), in accordance with the randomization schedule.	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).; Other Names: Conmana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression Free Survival (PFS) assessed by Investigator	PFS is defined as the time from randomization until the date of objective disease progression or death by any cause, whichever occurs first.	From randomization to objective disease progression or death, whichever came first, assessed up to 20 months
Objective Response Rate (ORR)	ORR is defined as the percentage (%) of participants with measurable disease with a best overall response of complete response (CR) or partial response (PR). ORR was based on investigator and IRC assessment.	At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months
Duration of Response (DoR)	DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death in the absence of disease progression. DoR was based on both Investigator and IRC assessment.	At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months
Disease Control Rate (DCR)	DCR is defined as the percentage (%) of participants who had a best overall response (BOR) of CR, PR or Stable disease (SD) ≥6 weeks prior to any progressive disease (PD) event, assessed by investigator and IRC.	At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months
Overall Survival (OS)	OS is defined as the time from randomization until the date of death due to any cause.	From randomization to date of death from any cause, whichever came first, up to 36 months
Intracranial ORR (iORR)	iORR is calculated as the ORR (CR+PR) of lesions in the brain for patients who have measurable disease in the brain at baseline. iORR was based on both Investigator and IRC assessment.	At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months
Intracranial PFS (iPFS)	iPFS is defined as time from randomization to intracranial disease progression or death due to any causes, assessed by investigator and IRC.	From randomization to objective intracranial disease progression or death, whichever came first, up to 20 months
Adverse event (AE)	AE is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study medication, whether or not considered related to the study medication. AEs are summarized by type, incidence, severity and relationship to study medication.	At baseline and every 3 weeks (±4 days) for the first 6 weeks, and then every 6 weeks (±4 days) until objective disease progression or meet other withdrawal criteria, up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire	The FACT-L questionnaire consists of several major aspects of life (Physical, social/family, emotional, and functional well-being) as well as lung cancer subscale (symptoms, cognitive function, regret of smoking). Scores for item ranging from 0 (not at all) to 4 (very much).	At baseline and every 6 weeks (±4 days) until disease progression, up to 20 months

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Shun Lu, PHD, Shanghai Chest Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2019
• Primary Completion (Actual): July 30, 2022
• Study Completion (Actual): July 15, 2025

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: D-0316; EGFR mutated NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: IBIO-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No