Non-small Cell Lung CancerPhase 1/2NCT03386955

BPI-7711 Capsule in Patients With EGFR Mutation T790M Positive Non-small Cell Lung Cancer

A Phase 1/2 study testing BPI-7711 Capsule in people with Non-small Cell Lung Cancer, run by Beta Pharma Shanghai at 4 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

Lung cancer has the highest incidence rate in China and is also a very common cancer in the world. BPI-7711 is a new drug developed for patients with non-small cell lung cancer. The purpose of this study is to evaluate the safety, efficacy and PK profile of BPI-7711. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Non-small Cell Lung Cancer
What is being tested?: BPI-7711 Capsule
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 215 participants
Where: 4 sitesChina
Study dates: 16 Aug 2017to 23 Dec 2021
Phase: Phase 1/2
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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects signs and dates the informed consent form before receiving any treatment or test sample collection related to the study.
Male or female, ≥18 and ≤75 years of age when signing the informed consent.
Locally advanced or metastatic non-small cell lung cancer (NSCLC) verified by histology or cytology, and no longer suitable for radical surgery or radiation therapy.
ECOG scoring (PS) of physical conditions 0-1, and there is no deterioration 2 weeks before enrolled to the study. The expected survival is not less than 12 weeks.
Phase I: Disease progressed after EGFR-TKI treatment as proved by radiological evidence. For dose level which does not provide satisfying efficacy in the escalation group, patients must receive chemo therapy before enrolled into that dose, unless not suitable for chemotherapy judged by investigator. Patients must have documented radiological progression before enrolled into the study. Phase IIa: Patients must be treatment- naïve for locally advanced or metastatic NSCLC. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) provided all other entry criteria are satisfied
At least 1 measurable lesion based on the RECIST1.1 criteria. If the subject has only 1 measurable lesion, the baseline CT must be performed before biospy or at least 14 days after biopsy. The lesion received radiotherapy does not count as measurable lesion or a biopsy lesion unless it shows obvious progression after radiotherapy. Brain metastases and irradiated lesions are not taken as target lesions.

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Prior to enrollment, a central laboratory testing report confirmed the tumor has EGFR positive gene mutation sensitive to EGFR-TKI treatment (including G719X, exon 19 loss, L858R, L861Q etc.).
Phase I: Central lab tissue tests confirm T790M positive for the biopsy, plasma, or cytology samples collected after imaging examination with clear disease progression post last treatment. Subject should provide formalin fixed and paraffin embedded tumor tissue block or 5 pieces of 4-5µm thick undyed slices, or should agree to do tumor tissue biopsy.
The clinical laboratory examination results shall meet the following criteria:
Blood platelet ≥100×10^9/L
Absolute neutrophil counting（ANC）≥1.5×10^9/L
Hemoglobin（Hgb）≥90 g/L
Total bilirubin (TBil) ≤1.5 times of upper normal limit（ULN） (≤3 times of ULN is allowed if there is liver metastasis)
Alanine aminotransferase (ALT) and aspertate aminotransferase (AST) ≤3 times of ULN (≤5 times of ULN is allowed if there is liver metastasis)
Creatinine ≤1.5times of ULN or creatinine clearance≥50 mL/min.
Mean resting corrected QT interval (QTc) ≤470 msec obtained from 3 electrocardiograms (ECGs).
If the subject is not taking anticoagulants, the International Standardization Ratio (INR) ≤1.5 and APTT ≤1.5 times of ULN. For patients who are being treated with heparin anticoagulant therapy, if these indicators have no abnormality, and then they can be enrolled. For subjects who are receiving warfarin anticoagulant therapy, within 28 days before enrolled into the study, relating to INR, use stable dose warfarin.
Able to swallow the study drug.
Female subjects should take effective contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential.
Male patient subjects are willing to use barrier contraception.
Except hair loss and stable below level 2 peripheral nerve toxicity, any clinical toxicity related to previous treatment before enrollment must restore to pre-treatment or level 1.

Who cannot join

Anti-cancer treatment with first/second generation of EGFR-TKI (e.g., Icotinib, gefitinib, erlotinib afatinib, dacomitinib, etc) within 8 days (approximately 5 times of half-life) before first dosing in the study.
Received treatment targeted for T790M positive mutation, or participated in clinical trials for such types of drugs, e.g., AZD9291, CO-1686 and other third-generation TKI therapy.
Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days prior to the first dose of study treatment.
Any of the following cardiac criteria: resting corrected QT interval (QTcF) > 470 msec; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, III-degree heart block, II-degree heart block, PR interval >250 msec; Factors that may increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure - New York Heart Association (NYHA) Class II-IV, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervals.
Past interstitial lung disease, drug induced interstitial lung disease, radiation pneumonia that needs steroid therapy, or any evidence of clinically. active interstitial lung disease.
The known active infection, such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infection. Patients with well-controlled hepatitis B can be enrolled to the study, and can receive antiviral treatment.

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Patients with other malignant tumor and still under treatment, or have recurrent or associated other malignant tumor within the last 5 years are not eligible. Cervical cancer in situ eradication therapy, non-melanoma skin cancer, superficial bladder tumor (noninvasive tumor), or carcinoma in situ with no recurrence, nor relevant treatment in 3 years after eradication treatment, may be eligible.
Judged by investigators, clear digestive tract disorder which may interfere with BPI-7711 absorption (for example, obvious uncontrolled inflammatory gastrointestinal diseases, abdominal colostomy within 6 months or past history of gastrointestinal perforation, intestinal wide excision and the need for tube feeding or parenteral fluids/nutrition supplementation).
Spinal cord compression, metastases of the meninges, and brain metastases with obvious symptoms. cannot be enrolled. The following cases of brain metastases without symptoms can be enrolled: Brain metastases without obvious symptoms diagnosed at screening visit, steroids and/or local treatment not required judged by investigator; Brain metastases without obvious symptoms after local treatment (such as radiotherapy), and steroids and/or antiepileptic therapy has stopped for at least 7 days before the first dosing of study drug.
Local radiotherapy to alleviate the disease within 1 week before first dosing of the study drug; more than 30% bone marrow radiotherapy or with a wide field of radiotherapy within 4 weeks before first dosing of the study drug.
≤4 weeks before major surgery or ≤2 weeks before minor surgery before the first day of administration of the study drug.
Any unstable factor or factors that may endanger the safety of the patients or affect the subjects' compliance to procedures and requirements of this study.
Leukocyte-depleted whole blood transfusion within the 120 days before collecting genetic testing samples.
Pregnant or breast-feeding women.
All subjects must have enough mental behavior ability, understand the nature and significance of the study, as well as the risks associated with this study.
Drug abuse, alcoholic addiction, medical and mental illness and social barriers which may interfere the subjects' participation in the study or affect study result evaluation judged by investigator. Any factor that the investigator believes may make the candidates not suitable to receive study drug. The candidates are unwilling or unable to comply with the requirements of the study protocol.

Trial locations and contacts

4 sites in 1 country.

China4 sites

Beijing Cancer Hospital
Beijing, Beijing Municipality
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality
Jiangsu Province Hospital
Nanjing, Jiangsu
The First Affiliated Hospital of Suzhou University
Suzhou, Jiangsu, 215006

Other trials in China

About this study

Official title: An Open-label, Single Arm, Phase I/IIa Study to Evaluate Safety, Dose Escalation Tolerability, Pharmacokinetics and Antineoplastic Activity of the BPI-7711 Capsule in Patients With EGFR Mutation Advanced or Recurrent NSCLC

Lung cancer has the highest incidence rate in China and is also a very common cancer in the world. BPI-7711 is a new drug developed for patients with non-small cell lung cancer.

The purpose of this study is to evaluate the safety, efficacy and PK profile of BPI-7711. The first part of the study will recruit 3~6 patients for different dose levels to evaluate safety. The dose will increase from the lowest level. The second part of the study is the dose expansion. Once efficacy is observed in the dose increasing process, additional 20~30 patients will be enrolled to further evaluate the anti-tumor efficacy. A recommended dose will be selected for Phase II study.

Read the detailed description

This is a single arm, open label study, including phase I (a "dose escalation" part and a "dose extension" part) and phase IIa.

Dose escalation: on the basis of the traditional "3+3" dose escalation plan; single dose PK test is added. The subjects of each dose group will first be given a single dose, and blood samples be collected for PK analysis. 7 days (wash-out period) after single dose delivery, an additional 21 days of continuous multiple dose delivery will be given as a treatment cycle to evaluate the dose limiting toxicity (DLT). The initial dose will be 30 mg once a day. In the initial dose group, the second subject will be enrolled and administered with the study drug 7 days after the first dosing (single dose) to the first subject. If there is no occurrence of serious or unexplainable safety event, the subsequent following-up subjects will be enrolled and receive the dose. If suspected safety event occurs, the investigator will discuss with the sponsor whether to delay dose delivery to the following-up subjects of the said group.

Every dose escalation group will enroll 3 to 6 subjects. Dose adjustment will be based on the following scheme:

If there is 0 case of DLT in 3 subjects of the initial dose group in the first treatment cycle, then the treatment dose of the subsequent 3 patients will be increased to level 2.
If there is 1 case of DLT in 3 subjects of the initial dose group in the first treatment cycle, then additional 3 patients will be enrolled in the group and accept the level 1 dose treatment.
If there is 0 case of DLT in the 3 new subjects, the dose will be increased to level 2.
If there is ≥1 case of DLT in the 3 new subjects, the principal investigator and the sponsor will discuss to determine the next step dose scheme.
If there are ≥2 cases of DLT in 3 subjects of the initial dose group, the principal investigator and the sponsor will meet to discuss the alternative dose delivery scheme.

The same dose escalation rules shall be applicable to the following dose groups. Based on available tolerance, safety, and PK data, recommended Phase II dose (RP2D) will be selected.

Dose extension group: If a certain dose is found to be safe and effective, dose expansion will be initiated and about 20-30 subjects will be enrolled into that dose level. There will be no DLT evaluation for subjects of the dose extension study.

Conditions: Non-small Cell Lung Cancer
Being tested: BPI-7711 Capsule
Keywords: non-small cell lung cancer, 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.

BPI-7711 CapsuleDrug
Also called BPI-7711, BPI7711 Capsule
Phase I: BPI-7711 capsule(30mg, 60mg, 120mg, 180mg, 240mg...) Phase IIa: BPI-7711 capsule(with recommend phase II dose)

Study groups in NCT03386955
Study group	Role	What they receive
BPI-7711 treatment	Experimental	Phase I: Patients in dose escalation group will receive single dose of BPI-7711 on day -7 and start receive the 21 days/cycle continuous treatment once a day after 7 day washout period. Patients in the extension group will receive BPI-7711 once a day with the selected doses. Phase IIa: Patients will receive BPI-7711 capsule(recommend phase 2 dose) as the first line treatment. Receives: Drug: BPI-7711 Capsule

What is being measured

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

Number of patients with dose limiting toxicity ( DLT).
DLT to be evaluated according to NCI CTCAE V4.03
Measured: From first dosing ( Day -7) to the last dosing of Cycle 1 ( Day 28).

Secondary outcomes (11)

Maximum plasma concentration (Cmax) of BPI-7711 and its main metabolites.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Day-7~Day-1 at designated time points.
Measured: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Peak Plasma Time (tmax) of BPI-7711 and its main metabolites after single dose.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Day-7~Day-1 at designated time points.
Measured: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Area under the plasma concentration versus time curve (AUC) of BPI-7711 and its main metabolites after single dose.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Day-7~Day-1 at designated time points.
Measured: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Clearance of BPI-7711 and its main metabolites after single dose.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Day-7~Day-1 at designated time points.
Measured: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Half life of BPI-7711 and its main metabolites after single dose.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Day-7~Day-1 at designated time points.
Measured: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Blood concentration of BPI-7711 and its main metabolites after single dose under steady state.
Collect and analyze the blood concentration data of BPI-7711 and its main metabolites on Cycle 1 Day1, Cycle Day 8, Cycle 1 Day 15 and Cycle 2 Day1 at designated time. points.
Measured: Pre-dose of Cycle1 Day1, 8, 15. Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h post dose on Cycle 2 Day1
Objective response rate (ORR) of BPI-7711 capsule.
Objective response rate evaluated by CT, MRI examination results according to RECIST 1.1.
Measured: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Best objective response (BOR) of BPI-7711 capsule.
Best objective response evaluated by CT, MRI examination results according to RECIST 1.1.
Measured: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Disease control rate ( DCR) of BPI-7711 capsule.
Disease control rate evaluated by CT, MRI examination results according to RECIST 1.1.
Measured: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Duration of response ( DoR) of BPI-7711 capsule.
Duration of response evaluated by CT, MRI examination results according to RECIST 1.1.
Measured: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Progression free survival (PFS) of BPI-7711 capsule.
Progression free survival evaluated by CT, MRI examination results according to RECIST 1.1.
Measured: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.

Timeline

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

16 Aug 201723 Dec 2021

First posted29 Dec 2017
Study start16 Aug 2017
Primary completion23 Dec 2021
Study completion23 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 215 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03386955
Sponsor's protocol ID: BPI-7711-2015-001
Status last verified: May 2022
First submitted: 4 Nov 2017
Last updated: 16 May 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Yang S, Wu S, Zhao Y, Chen G, Zhu B, Li X, Wang K, Shi J, Cang S, Yao W, Fan Y, Fang J, Zhang L, Zhou J, Wu L, Zheng R, Huang M, Pan Y, Yang Z, Sun M, Yu H, Wang D, Huang J, Wang L, Shu Y, Chen Z, Liu C, Li J, Liu J, Sun S, Guo Y, Meng Z, Liu Z, Han Z, Wu G, Lu H, Ma R, Hu S, Zhao G, Zhang L, Liu Z, Xie C, Zhong D, Zhao H, Bi M, Yi S, Guo S, Yi T, Li W, Lin Y, Chen Z, Zhuang Z, Guo Z, Greco M, Wang T, Zhou A, Shi Y. Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies. Lung Cancer. 2023 Jun;180:107194. doi: 10.1016/j.lungcan.2023.107194. Epub 2023 Apr 17.
PubMed 37163774
Shi Y, Zhou J, Zhao Y, Zhu B, Zhang L, Li X, Fang J, Shi J, Zhuang Z, Yang S, Wang D, Yu H, Zhang L, Zheng R, Greco M, Wang T. Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study. BMC Med. 2023 Jan 8;21(1):11. doi: 10.1186/s12916-022-02692-8.
PubMed 36617560
Shi Y, Zhao Y, Yang S, Zhou J, Zhang L, Chen G, Fang J, Zhu B, Li X, Shu Y, Shi J, Zheng R, Wang D, Yu H, Huang J, Zhuang Z, Wu G, Zhang L, Guo Z, Greco M, Li X, Zhang Y. Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study. J Thorac Oncol. 2022 May;17(5):708-717. doi: 10.1016/j.jtho.2022.01.015. Epub 2022 Feb 15.
PubMed 35181498

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 16 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single Arm, Phase I/IIa Study to Evaluate Safety, Dose Escalation Tolerability, Pharmacokinetics and Antineoplastic Activity of the BPI-7711 Capsule in Patients With EGFR Mutation Advanced or Recurrent NSCLC
ClinicalTrials.gov ID: NCT03386955
Acronym / sponsor ID: BPI-7711-2015-001
Conditions: Non-small Cell Lung Cancer
Keywords: non-small cell lung cancer, NSCLC
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 215 participants (actual)
Lead sponsor: Beta Pharma ShanghaiIndustry (pharma, biotech, devices)
Study start: 16 Aug 2017 (actual)
Primary completion: 23 Dec 2021 (actual)
Study completion: 23 Dec 2021 (actual)
First posted: 29 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Lung cancer has the highest incidence rate in China and is also a very common cancer in the world. BPI-7711 is a new drug developed for patients with non-small cell lung cancer.

Detailed description

This is a single arm, open label study, including phase I (a "dose escalation" part and a "dose extension" part) and phase IIa.

Every dose escalation group will enroll 3 to 6 subjects. Dose adjustment will be based on the following scheme:

If there is 0 case of DLT in 3 subjects of the initial dose group in the first treatment cycle, then the treatment dose of the subsequent 3 patients will be increased to level 2.
If there is 1 case of DLT in 3 subjects of the initial dose group in the first treatment cycle, then additional 3 patients will be enrolled in the group and accept the level 1 dose treatment.
If there is 0 case of DLT in the 3 new subjects, the dose will be increased to level 2.
If there is ≥1 case of DLT in the 3 new subjects, the principal investigator and the sponsor will discuss to determine the next step dose scheme.
If there are ≥2 cases of DLT in 3 subjects of the initial dose group, the principal investigator and the sponsor will meet to discuss the alternative dose delivery scheme.

The same dose escalation rules shall be applicable to the following dose groups. Based on available tolerance, safety, and PK data, recommended Phase II dose (RP2D) will be selected.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BPI-7711 treatment	Experimental	Drug: BPI-7711 CapsulePhase I: Patients in dose escalation group will receive single dose of BPI-7711 on day -7 and start receive the 21 days/cycle continuous treatment once a day after 7 day washout period. Patients in the extension group will receive BPI-7711 once a day with the selected doses. Phase IIa: Patients will receive BPI-7711 capsule(recommend phase 2 dose) as the first line treatment.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

Subjects signs and dates the informed consent form before receiving any treatment or test sample collection related to the study.
Male or female, ≥18 and ≤75 years of age when signing the informed consent.
Locally advanced or metastatic non-small cell lung cancer (NSCLC) verified by histology or cytology, and no longer suitable for radical surgery or radiation therapy.
ECOG scoring (PS) of physical conditions 0-1, and there is no deterioration 2 weeks before enrolled to the study. The expected survival is not less than 12 weeks.
Phase I: Disease progressed after EGFR-TKI treatment as proved by radiological evidence. For dose level which does not provide satisfying efficacy in the escalation group, patients must receive chemo therapy before enrolled into that dose, unless not suitable for chemotherapy judged by investigator. Patients must have documented radiological progression before enrolled into the study. Phase IIa: Patients must be treatment- naïve for locally advanced or metastatic NSCLC. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) provided all other entry criteria are satisfied

Key exclusion criteria (16 listed)

Anti-cancer treatment with first/second generation of EGFR-TKI (e.g., Icotinib, gefitinib, erlotinib afatinib, dacomitinib, etc) within 8 days (approximately 5 times of half-life) before first dosing in the study.
Received treatment targeted for T790M positive mutation, or participated in clinical trials for such types of drugs, e.g., AZD9291, CO-1686 and other third-generation TKI therapy.
Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days prior to the first dose of study treatment.
Any of the following cardiac criteria: resting corrected QT interval (QTcF) > 470 msec; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, III-degree heart block, II-degree heart block, PR interval >250 msec; Factors that may increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure - New York Heart Association (NYHA) Class II-IV, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervals.
Past interstitial lung disease, drug induced interstitial lung disease, radiation pneumonia that needs steroid therapy, or any evidence of clinically. active interstitial lung disease.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BPI-7711 CapsuleAlso: BPI-7711, BPI7711 CapsulePhase I: BPI-7711 capsule(30mg, 60mg, 120mg, 180mg, 240mg...) Phase IIa: BPI-7711 capsule(with recommend phase II dose)	Drug	BPI-7711 treatment

Primary outcome

Number of patients with dose limiting toxicity ( DLT).
Time frame: From first dosing ( Day -7) to the last dosing of Cycle 1 ( Day 28).
DLT to be evaluated according to NCI CTCAE V4.03

11 secondary outcomes

Maximum plasma concentration (Cmax) of BPI-7711 and its main metabolites.
Time frame: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Peak Plasma Time (tmax) of BPI-7711 and its main metabolites after single dose.
Time frame: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Area under the plasma concentration versus time curve (AUC) of BPI-7711 and its main metabolites after single dose.
Time frame: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Clearance of BPI-7711 and its main metabolites after single dose.
Time frame: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Half life of BPI-7711 and its main metabolites after single dose.
Time frame: Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.
Blood concentration of BPI-7711 and its main metabolites after single dose under steady state.
Time frame: Pre-dose of Cycle1 Day1, 8, 15. Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h post dose on Cycle 2 Day1
Objective response rate (ORR) of BPI-7711 capsule.
Time frame: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Best objective response (BOR) of BPI-7711 capsule.
Time frame: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Disease control rate ( DCR) of BPI-7711 capsule.
Time frame: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Duration of response ( DoR) of BPI-7711 capsule.
Time frame: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.
Progression free survival (PFS) of BPI-7711 capsule.
Time frame: At screening, and every two cycles from the first multiple dose on Cycle 1 Day 1( 21 days as one cycle) until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2022.
Derived from this study: PubMed 37163774Yang S, Wu S, Zhao Y, Chen G, Zhu B, Li X, Wang K, Shi J, Cang S, Yao W, Fan Y, Fang J, Zhang L, Zhou J, Wu L, Zheng R, Huang M, Pan Y, Yang Z, Sun M, Yu H, Wang D, Huang J, Wang L, Shu Y, Chen Z, Liu C, Li J, Liu J, Sun S, Guo Y, Meng Z, Liu Z, Han Z, Wu G, Lu H, Ma R, Hu S, Zhao G, Zhang L, Liu Z, Xie C, Zhong D, Zhao H, Bi M, Yi S, Guo S, Yi T, Li W, Lin Y, Chen Z, Zhuang Z, Guo Z, Greco M, Wang T, Zhou A, Shi Y. Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies. Lung Cancer. 2023 Jun;180:107194. doi: 10.1016/j.lungcan.2023.107194. Epub 2023 Apr 17.
Derived from this study: PubMed 36617560Shi Y, Zhou J, Zhao Y, Zhu B, Zhang L, Li X, Fang J, Shi J, Zhuang Z, Yang S, Wang D, Yu H, Zhang L, Zheng R, Greco M, Wang T. Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study. BMC Med. 2023 Jan 8;21(1):11. doi: 10.1186/s12916-022-02692-8.
Derived from this study: PubMed 35181498Shi Y, Zhao Y, Yang S, Zhou J, Zhang L, Chen G, Fang J, Zhu B, Li X, Shu Y, Shi J, Zheng R, Wang D, Yu H, Huang J, Zhuang Z, Wu G, Zhang L, Guo Z, Greco M, Li X, Zhang Y. Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study. J Thorac Oncol. 2022 May;17(5):708-717. doi: 10.1016/j.jtho.2022.01.015. Epub 2022 Feb 15.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yuankai Shi principal investigator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BPI-7711 Capsule in people with Non-small Cell Lung Cancer, run by Beta Pharma Shanghai at 4 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 21 inclusion and 16 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 16 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

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?

Number of patients with dose limiting toxicity ( DLT). (time frame: From first dosing ( Day -7) to the last dosing of Cycle 1 ( Day 28).). 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 NCT03386955, which also lists 3 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 16 May 2022.