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Non-Small Cell Lung CancerPhase 2/3NCT04206072

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

A Phase 2/3 study testing D-0316 Capsule and Icotinib Hydrochloride Tablets in people with Non-Small Cell Lung Cancer and EGFR Gene Mutation, run by Betta Pharmaceuticals Co., Ltd. at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
D-0316 Capsule and Icotinib Hydrochloride Tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
362 participants
Where
2 sitesChina
Study dates
24 Dec 2019to 15 Jul 2025
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

China2 sites
  • The First Affiliated Hospital of Medical School of Zhejiang University

    Hangzhou, Zhejiang

  • Liuzhou Workers Hospital

    Liuzhou

Other trials in China

About this study

Official title: 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).

Read the 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.

Being tested
D-0316 Capsule, Icotinib Hydrochloride Tablets
Keywords
D-0316, EGFR mutated NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • D-0316 CapsuleDrug

    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 Hydrochloride TabletsDrug

    Also called Conmana

    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).

Study groups in NCT04206072
Study groupRoleWhat they receive
D-0316ExperimentalD-0316 (75 mg or 100 mg orally, once daily), in accordance with the randomization schedule.
Receives: Drug: D-0316 Capsule
IcotinibActive comparatorIcotinib (125 mg orally, three times daily), in accordance with the randomization schedule.
Receives: Drug: Icotinib Hydrochloride Tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)
  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. Overall Survival (OS)

    OS is defined as the time from randomization until the date of death due to any cause.

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

  6. 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.

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

  7. 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.

    Measured: From randomization to objective intracranial disease progression or death, whichever came first, up to 20 months

  8. 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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2019
  2. Study start24 Dec 2019
  3. Primary completion30 Jul 2022
  4. Study completion15 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
362 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04206072
Sponsor's protocol ID
IBIO-103
Status last verified
Aug 2025
First submitted
10 Dec 2019
Last updated
11 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37244266
  • 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.

    PubMed 35724798

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing D-0316 Capsule and Icotinib Hydrochloride Tablets in people with Non-Small Cell Lung Cancer and EGFR Gene Mutation, run by Betta Pharmaceuticals Co., Ltd. at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Progression Free Survival (PFS) assessed by IRC (time frame: From randomization to objective disease progression or death, whichever came first, assessed up to 20 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04206072, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.

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