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

NCT03386955 | Completed Phase 1 DMC

• 1 other identifier: BPI-7711-2015-001
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity ( DLT).

  DLT to be evaluated according to NCI CTCAE V4.03

  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.

  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.

  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.

  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.

  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.

  Pre-dose, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h, 72h, 120h, 144h post first dose on Day -7.

Other Outcomes (2)

• EGFR mutation testing.

  At screening and every two cycles( 21 days as a cycle) from Cycle 1 Day1 until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.

• T790M mutation testing.

  At screening and every two cycles( 21 days as a cycle) from Cycle 1 Day1 until the date of first documented progression, death or withdrawal from study, whichever came first, assessed up to 20 months.

Study Arms (1)

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.

Drug: BPI-7711 Capsule

Interventions

BPI-7711 Capsule DRUG

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

Also known as: BPI-7711, BPI7711 Capsule

BPI-7711 treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Beta Pharma Shanghai: lead

Study Sites (4)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Location

The First Affiliated Hospital of Suzhou University

Suzhou, Jiangsu, 215006, China

Location

Related Publications (3)

• 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.

  PMID: 37163774 DERIVED

• 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.

  PMID: 36617560 DERIVED

• 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.

  PMID: 35181498 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

rezivertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yuankai Shi

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2017
• First Posted: December 29, 2017
• Study Start: August 16, 2017
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: May 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)