Clinical trial NCT03861156: D-0316 in Patients With EGFR Positive Non Small Cell Lung Cancer
Official title: A Phase II Study to Assess the Safety and Efficacy of D-0316 in Patients With Locally Advanced/Metastatic Non Small Cell Lung Cancer Whose Tumors Are Epidermal Growth Factor Receptor Mutation Positive
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Solid Tumor
NSCLC
EGFR T790M
Lead sponsor: InventisBio Co., Ltd
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of D-0316 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

Detailed description: This is a phase II, open label, single arm study assessing the safety and efficacy of D-0316 (Firstly, D-0316 was orally given 75mg for a cycle(21 days), if tolerated, the dose will be increased to 100mg. Otherwise, the dose will be maintained at 75mg.) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC,who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The primary objective of the study is to assess the efficacy of D-0316 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.

Eligibility criteria: Inclusion Criteria:

* Aged at least 18 years.
* Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic.
* Radiological documentation of disease progression while on a previous continuous treatment with an first or second generation of EGFR TKI e.g. gefitinib or erlotinib.
* patients must also have confirmation of tumour T790M mutation status (confirmed positive) after disease progression on the prior EGFR TKI.
* Eastern cooperative oncology group performance status (ECOG PS) of 0-1.
* a minimum life expectancy of 12 weeks.
* At least one lesion, not previously irradiated during the study screening period, that can be accurately measured at baseline according to RECIST 1.1.
* Agree to use routine adequate and effective contraceptive measures during the entire study period and within 6 weeks after the last dose pre-menopausal fertility possible; Female patients need to exclude pregnancy (ie negative pregnancy test) and in non-lactation period.

Exclusion Criteria:

* Treatment with a first or second generation of EGFR-TKI within 10 days of study entry; previous treatment with a third generation of EGFR-TKI.
* Unresolved toxicities from prior therapy.
* Unstable spinal cord compression/brain metastases.
* Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection.
* QTcF≥470 msec（female）or QTcF≥450 msec（male）during the screening period.
* Severe respiratory diseases such as interstitial lung disease, severe asthma, pulmonary embolism, etc.
* previous treatment with 2 or more lines of Chemotherapy or immunotherapy.

Primary outcomes:
measure: Objective response rate based on independent radiology review
timeFrame: 24 months
Secondary outcomes:
measure: Progression-free survival (PFS) as assessed by independent radiology review and investigator
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
measure: Duration of response(DoR)
timeFrame: 24 months
measure: Disease control rate(DCR)
timeFrame: 24 months
measure: Intracranial Progression-free survival(iPFS)
timeFrame: 36 months
measure: Intracranial objective response rate(iORR)
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun Lu
role: STUDY_CHAIR
References:
citation: 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.