NSCLCPhase 1EGFRNCT06362980
A Study With BPI-1178 and Osimertinib in Advanced Non-small Cell Lung Cancer Patients With EGFR Mutations
A Phase 1 study testing BPI-1178 and Osimertinib in people with NSCLC, run by National Cancer Center, China at 1 site in China.
Trial summary
BPI-1178 is a novel, orally administered inhibitor of both cyclin-dependent kinase 4 (CDK4) and CDK6 kinase activity. This open-label investigator-initiated trial (IIT) phase I study was designed to evaluate the safety and efficacy of oral BPI-1178 in combination with osimertinib in patients with locally advanced or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- BPI-1178 and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 22 May 2024to 1 Apr 2026
- Phase
- Phase 1
- 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
- Participants must meet all of the following inclusion criteria to be eligible for this study:
- Signed written informed consent and ability to comply with the scheduled visits and study procedures outlined in the protocol.
- Age ≥ 18 years, any gender.
- Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (mainly adenocarcinoma) not suitable for curative surgery or radiation therapy.
- ECOG Performance Status (ECOG PS) score of 0-1. Expected survival of at least 12 weeks.
- Prior treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) targeted therapy, with radiological evidence of disease progression. The last treatment before enrollment must show radiological evidence of disease progression, intolerance to chemotherapy toxicity, or the patient being ineligible for standard treatment or unable to tolerate the current treatment regimen.
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- At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria that has not been previously irradiated.
- Tissue, plasma, or cytological samples collected after disease progression confirmed by imaging following treatment with a third-generation EGFR TKI, demonstrating an EGFR-positive gene mutation sensitive to EGFR TKI treatment (including exon 19 deletion, 21 L858R mutation, etc.), with or without T790M mutation.
- Adequate organ and bone marrow function, with clinical laboratory test results meeting the following criteria:
- Hematology: Neutrophils ≥ 1.5 × 10^9/L; Platelets ≥ 100 × 10^9/L; Hemoglobin (Hgb) ≥ 100 g/L;
- Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) (≤3 × ULN for patients with Gilbert's syndrome); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN;
- Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate (CCr, Cockcroft-Gault formula) ≥ 50 mL/min; Semi-quantitative urine testing (e.g., urine dipstick) result showing urine protein < 2+; patients with urine protein ≥ 2+ at baseline should undergo a 24-hour urine collection, and the protein content in the urine within 24 hours should be < 1g;
- Coagulation function: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) both ≤ 1.5 × ULN;
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%;
- At rest, male QTcF < 450 msec or female QTcF < 470 msec.
- Ability to swallow oral medications.
- Reproductive-age female patients must agree to use effective contraception throughout the study period until 60 days after discontinuing BPI-1178 and osimertinib. Female patients must have a negative pregnancy test result before the start of treatment or prove the absence of pregnancy possibility. Male patients must agree to use effective contraception throughout the study period until 120 days after discontinuing BPI-1178 and osimertinib.
- Apart from stable Grade 2 peripheral neuropathy (CTCAE v5.0) and alopecia, any treatment-related clinical toxicity before enrollment must have recovered to baseline or Grade 1.
- All patients must have sufficient mental capacity to understand the nature, significance of the study, and risks associated with the study.
Who cannot join
- Subjects with any of the following cannot be included in this study:
- History of prior or current use of anti-tumor drugs targeting CDK4/6.
- Individuals with allergies or a history of severe allergic reactions.
- Tissue, plasma, or cytological samples collected after radiological confirmation of disease progression, with testing confirming the presence of specific therapeutic targets such as anaplastic lymphoma kinase (ALK), BRAF V600E, or retinoblastoma (Rb) protein loss.
- Received the last dose of anti-tumor treatment (chemotherapy, targeted therapy, investigational drugs, immunotherapy, tumor embolization, herbal medicine for anti-tumor purposes, etc.) within the 2 weeks preceding the start of study drug administration.
- Presence of third-space effusion (such as significant pleural or abdominal fluid) that cannot be controlled by drainage or other methods.
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- Long-term use of steroids is required.
- Unresolved hypokalemia and hypomagnesemia at the time of enrollment.
- Meets any of the following criteria: Various clinically significant arrhythmias and conduction abnormalities, such as atrial fibrillation, complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 msec; various factors that may increase the risk of QT interval prolongation or arrhythmia events, such as symptomatic heart failure - New York Heart Association (NYHA) class II-IV, congenital long QT syndrome, Brugada syndrome, history of QT interval prolongation (male > 470 ms, female > 480 ms) or torsades de pointes (TdP), family history of long QT syndrome or unexplained sudden death before the age of 40, various concomitant medications that may prolong QT interval; within the 6 months before starting the study drug, had the following diseases, including unstable angina, myocardial infarction, cerebrovascular accident, pulmonary embolism, etc., or underwent cardiac revascularization surgery.
- History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any clinically evident active interstitial lung disease.
- Known active infections, such as hepatitis B (HBsAg positive and hepatitis B virus (HBV) DNA copy number ≥ 200 IU/ml), hepatitis C, and human immunodeficiency virus (HIV) infection.
- Cannot be included if there has been a relapse or concurrent malignancy in the past 5 years. Cervical cancer treated with curative intent, non-melanoma skin cancer, superficial bladder tumors (non-invasive tumors), or cancer with no recurrence for 3 years after curative treatment can be considered for inclusion.
- History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- Various factors judged by the investigator to potentially affect the intake and absorption of BPI-1178 or osimertinib, including gastrointestinal factors (such as uncontrolled inflammatory gastrointestinal diseases, history of abdominal fistula or gastrointestinal perforation within 6 months, extensive small intestine resection requiring enteral or parenteral supplementation, inability to swallow, chronic diarrhea, intestinal obstruction, etc.).
- Spinal cord compression, leptomeningeal metastases, or symptomatic brain metastases cannot be included. Asymptomatic patients with brain metastases may be allowed to participate under the following conditions: Asymptomatic brain metastases discovered during screening, determined by the investigator not to require steroids and/or local treatment; asymptomatic brain metastases treated with local therapy (such as radiation) with the patient discontinuing steroids and/or antiepileptic treatment for at least 7 days before the first administration of BPI-1178 in combination with osimertinib.
- Major surgery (craniotomy, thoracotomy, or laparotomy) or severe unhealed wounds, ulcers, or fractures within the 4 weeks preceding the start of study drug administration.
- Local radiation therapy for symptom relief within 1 week before the first administration of the study drug; bone marrow radiation therapy or extensive radiation therapy exceeding 30% within 4 weeks before the first administration of the study drug.
- Presence of factors, according to the investigator's judgment, that may interfere with patient participation in the trial or the assessment of study results, such as substance abuse, alcohol addiction, medical, psychiatric illness, and social disorders, or any factors that the investigator deems the patient unsuitable for receiving the study drug (such as severe hypertension, diabetes, thyroid disease, severe infection, portal hypertension, cirrhosis, etc.). Patients who were unwilling or unable to comply with the requirements of this study protocol will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single-arm, Investigator-initiated Phase I Clinical Study Evaluating BPI-1178 Capsules in Combination With Osimertinib Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With EGFR Mutations
BPI-1178 is a novel, orally administered inhibitor of both cyclin-dependent kinase 4 (CDK4) and CDK6 kinase activity. This open-label investigator-initiated trial (IIT) phase I study was designed to evaluate the safety and efficacy of oral BPI-1178 in combination with osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) Mutations.
Read the detailed description
This study is an open-label, single-arm, single-center clinical study initiated by the researcher. The plan is to enroll 20 patients with locally advanced or metastatic NSCLC harboring EGFR mutations. The study aims to assess the safety and conduct preliminary observations on the efficacy of BPI-1178 capsules in combination with osimertinib in treating locally advanced or metastatic EGFR mutation-positive NSCLC patients who have developed resistance to osimertinib.
- Conditions
- NSCLC
- Being tested
- BPI-1178, Osimertinib
- Keywords
- NSCLC, EGFR Gene Mutation, BPI-1178, Osimertinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPI-1178Drug
Also called BPI-1178 capsule
200 or 300 mg, oral, QD
OsimertinibDrug
Also called Tagrisso
80mg, oral, QD
| Study group | Role | What they receive |
|---|---|---|
| BPI-1178 plus Osimertinib treatment | Experimental | Patients will undergo treatment with a combination of BPI-1178 capsules and osimertinib tablets. Patients will orally receive a single dose of BPI-1178 (200 or 300 mg) capsules and osimertinib tablets (80 mg). After a 7-day washout period, continuous dosing will commence on the 8th day. During the continuous dosing phase, BPI-1178 capsules and osimertinib tablets will be administered once daily, with a treatment cycle consisting of 28 days. Receives: Drug: BPI-1178; Drug: Osimertinib |
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 will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
Measured: From first dosing (Day 7) to Day 28 of Cycle 1 (28 days/cycle)
Secondary outcomes (10)
Objective Response Rate (ORR)
The ORR is defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
Measured: Up to approximately 15 months
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects with the best overall response of complete response (CR), partial response (PR), or stable disease (SD).
Measured: Up to approximately 15 months
Duration of Response (DoR)
In subjects with the best overall response of complete response (CR) or partial response (PR), it refers to the time from the initial occurrence of complete or partial response to the occurrence of disease progression or death for any reason (whichever comes first).
Measured: Up to approximately 15 months
Progression-Free Survival (PFS)
PFS is defined as the duration from the first study treatment until the onset of disease progression or death from any cause for the subjects.
Measured: Up to approximately 15 months
Overall Survival (OS)
OS is defined as the duration from the initial study treatment to death from any cause among the subjects.
Measured: Up to approximately 15 months
Intracranial ORR (iORR)
The intracranial ORR is defined as the proportion of subjects with an intracranial best overall response of complete response (CR) or partial response (PR).
Measured: Up to approximately 15 months
Intracranial DCR (iDCR)
The intracranial DCR is defined as the proportion of subjects with an intracranial best overall response of complete response (CR), partial response (PR), or stable disease (SD).
Measured: Up to approximately 15 months
Intracranial DoR (iDoR)
In subjects with an intracranial best overall response of complete response (CR) or partial response (PR), it refers to the duration from the first initial occurrence of complete or partial response to the occurrence of intracranial disease progression or death for any reason (whichever comes first).
Measured: Up to approximately 15 months
Intracranial Time to Progression (iTTP)
Intracranial TTP is defined as the duration from the initiation of the first study treatment to the occurrence of intracranial disease progression among the subjects.
Measured: Up to approximately 15 months
Intracranial PFS (iPFS)
Intracranial PFS is defined as the duration from the first study treatment until the onset of intracranial disease progression or death from any cause for the subjects.
Measured: Up to approximately 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2024
- Study start22 May 2024
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Center, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Puyuan Xing, National Cancer Center, China
- Investigators
- Puyuan Xing, Doctorate, Principal investigator, Department of Medical Oncology, National Cancer Center, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06362980
- Sponsor's protocol ID
- BPI-1178-IIT01
- Acronym
- EGFR
- Status last verified
- Jul 2024
- First submitted
- 28 Mar 2024
- Last updated
- 10 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Investigator-initiated Phase I Clinical Study Evaluating BPI-1178 Capsules in Combination With Osimertinib Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With EGFR Mutations
- ClinicalTrials.gov ID
- NCT06362980
- Acronym / sponsor ID
- EGFR / BPI-1178-IIT01
- Conditions
- NSCLC
- Keywords
- NSCLC, EGFR Gene Mutation, BPI-1178, Osimertinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National Cancer Center, ChinaUniversity, hospital or other
- Study start
- 22 May 2024 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 12 Apr 2024 (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.
BPI-1178 is a novel, orally administered inhibitor of both cyclin-dependent kinase 4 (CDK4) and CDK6 kinase activity. This open-label investigator-initiated trial (IIT) phase I study was designed to evaluate the safety and efficacy of oral BPI-1178 in combination with osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) Mutations.
Detailed description
This study is an open-label, single-arm, single-center clinical study initiated by the researcher. The plan is to enroll 20 patients with locally advanced or metastatic NSCLC harboring EGFR mutations. The study aims to assess the safety and conduct preliminary observations on the efficacy of BPI-1178 capsules in combination with osimertinib in treating locally advanced or metastatic EGFR mutation-positive NSCLC patients who have developed resistance to osimertinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BPI-1178 plus Osimertinib treatment | Experimental | Drug: BPI-1178, Drug: OsimertinibPatients will undergo treatment with a combination of BPI-1178 capsules and osimertinib tablets. Patients will orally receive a single dose of BPI-1178 (200 or 300 mg) capsules and osimertinib tablets (80 mg). After a 7-day washout period, continuous dosing will commence on the 8th day. During the continuous dosing phase, BPI-1178 capsules and osimertinib tablets will be administered once daily, with a treatment cycle consisting of 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must meet all of the following inclusion criteria to be eligible for this study:
- Signed written informed consent and ability to comply with the scheduled visits and study procedures outlined in the protocol.
- Age ≥ 18 years, any gender.
- Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (mainly adenocarcinoma) not suitable for curative surgery or radiation therapy.
- ECOG Performance Status (ECOG PS) score of 0-1. Expected survival of at least 12 weeks.
Key exclusion criteria (18 listed)
- History of prior or current use of anti-tumor drugs targeting CDK4/6.
- Individuals with allergies or a history of severe allergic reactions.
- Tissue, plasma, or cytological samples collected after radiological confirmation of disease progression, with testing confirming the presence of specific therapeutic targets such as anaplastic lymphoma kinase (ALK), BRAF V600E, or retinoblastoma (Rb) protein loss.
- Received the last dose of anti-tumor treatment (chemotherapy, targeted therapy, investigational drugs, immunotherapy, tumor embolization, herbal medicine for anti-tumor purposes, etc.) within the 2 weeks preceding the start of study drug administration.
- Presence of third-space effusion (such as significant pleural or abdominal fluid) that cannot be controlled by drainage or other methods.
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-1178Also: BPI-1178 capsule200 or 300 mg, oral, QD | Drug | BPI-1178 plus Osimertinib treatment |
| OsimertinibAlso: Tagrisso80mg, oral, QD | Drug | BPI-1178 plus Osimertinib treatment |
Primary outcome
Number of patients with dose-limiting toxicity (DLT)
Time frame: From first dosing (Day 7) to Day 28 of Cycle 1 (28 days/cycle)
DLT will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
10 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to approximately 15 months
Disease Control Rate (DCR)
Time frame: Up to approximately 15 months
Duration of Response (DoR)
Time frame: Up to approximately 15 months
Progression-Free Survival (PFS)
Time frame: Up to approximately 15 months
Overall Survival (OS)
Time frame: Up to approximately 15 months
Intracranial ORR (iORR)
Time frame: Up to approximately 15 months
Intracranial DCR (iDCR)
Time frame: Up to approximately 15 months
Intracranial DoR (iDoR)
Time frame: Up to approximately 15 months
Intracranial Time to Progression (iTTP)
Time frame: Up to approximately 15 months
Intracranial PFS (iPFS)
Time frame: Up to approximately 15 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- 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.
Puyuan Xing, Doctorate principal investigator
Department of Medical Oncology, National Cancer Center, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BPI-1178 and Osimertinib in people with NSCLC, run by National Cancer Center, China at 1 site 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 19 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Puyuan Xing, Doctorate (+86-10-87787421, xingpuyuan@cicams.ac.cn), or a site near the patient. 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 Day 28 of Cycle 1 (28 days/cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jul 2024.