This is an open label, single arm Phase I study, including a "dose escalation" part and a
"dose extension" part. Dose extension will be initiated during the process of dose
escalation: once a dose is found to be safe and effective (evaluated according to objective
response rate [ORR]) during escalation, then that dose will be extended to enroll more
patients; at the same time, dose escalation will further continue in order to find out a
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
Every dose escalation group will enroll 3 to 6 subjects. Dose adjustment will be based on the
- 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
- 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
- If there is 0 case of DLT in the 3 new subjects, the dose will be increased to
- 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, in the dose escalation group, it is found that certain dose is safe
and effective, then dose expansion will be initiated and about 20-30 additional subjects will
be enrolled into this dose level and treated with 21 days as a cycle. The said dose extension
group will be ended in advance (less than 30 subjects) if efficacy found to be unsatisfying
after discussed by the investigator and the sponsor. There will be no DLT evaluation for
subjects of the dose extension study.
- 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
- 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.
- 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.
- 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 at 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.
- Previous local test reports confirmed the tumor has EGFR positive gene mutation
sensitive to EGFR-TKI treatment (including G719X, exon 19 loss, L858R, L861Q etc.).
- Central lab tissue tests confirm T790M positive for the biopsy 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:
1. Blood platelet ≥100×109/L
2. Absolute neutrophil counting（ANC）≥1.5×109/L
3. Hemoglobin（Hgb）≥90 g/L
4. Total bilirubin (TBil) ≤1.5 times of upper normal limit（ULN）
5. Alanine aminotransferase (ALT) and aspertate aminotransferase (AST) ≤3 times of
ULN (≤5 times of ULN is allowed if there is liver metastasis)
6. Creatinine ≤1.5times of ULN or creatinine clearance≥50 mL/min.
7. Mean resting corrected QT interval (QTc) ≤470 msec obtained from 3
8. 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 baseline or
- Anti-cancer treatment with EGFR-TKI (e.g., Icotinib, gefitinib or erlotinib) 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
- 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:
Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms
(ECGs); Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG eg, complete left bundle branch block, third degree heart block, second 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.
- 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
- 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.
- Need of legal guardian to sign the informed consent on behalf of the subjects based on
any reason. 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,
and be able to personally sign the informed consent.
- 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.