Trial Title:
A Phase I Study of CFT8919 in Patients With Advanced NSCLC
NCT ID:
NCT06641609
Condition:
Non-Small Cell Lung Cancer With EGFR Mutation
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
Non-small cell lung cancer
EGFR mutation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dose-Escalation (Phase Ia) CFT8919 capsule
Description:
Phase 1a，enrolled, eligible patients receive CFT8919 150-900mg twice daily.
Arm group label:
Dose-Escalation (Phase Ia)
Other name:
CFT8919
Intervention type:
Drug
Intervention name:
Dose-Expansion (Phase Ib) CFT8919 capsule
Description:
Phase 1b，enrolled, eligible patients receive CFT8919 RP2D twice daily.
Arm group label:
Dose-Expansion (Phase Ib)
Other name:
CFT8919
Intervention type:
Drug
Intervention name:
Cohort-Expansion (Phase Ic) CFT8919 capsule
Description:
Phase 1c，enrolled, eligible patients receive CFT8919 RP2D twice daily.
Arm group label:
Cohort-Expansion (Phase Ic)
Other name:
CFT8919
Summary:
The goal of this clinical trial is to evaluate the safety, tolerability,
pharmacokinetics, and antitumor activity of CFT8919 capsules in patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations. The
main questions it aims to answer are:
- What is the maximum tolerated dose (MTD) of CFT8919?
- Does CFT8919 demonstrate antitumor activity in these patients?
Participants will:
- Take CFT8919 capsules at different doses.
- Undergo regular assessments for safety, pharmacokinetics, and tumor response.
Researchers will compare different dose levels to determine the best balance between
safety and efficacy.
Detailed description:
This is a Phase I clinical study designed to evaluate the safety, tolerability,
pharmacokinetics, and antitumor activity of CFT8919 capsules in patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) who carry EGFR mutations. The
study includes three parts: dose-escalation, dose-expansion, and cohort-expansion. The
primary objectives are to determine the maximum tolerated dose (MTD) in the
dose-escalation phase and to assess the antitumor efficacy in the cohort-expansion phase.
Secondary objectives include assessing pharmacokinetic parameters, objective response
rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall
survival (OS). Exploratory objectives will evaluate biomarkers and the relationship
between drug exposure and treatment outcomes.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Dose-Escalation and Dose-Expansion Phases: Patients with histologically or
cytologically confirmed locally advanced or metastatic non-small cell lung cancer
(NSCLC) harboring the EGFR-L858R mutation, who have failed standard treatment
(disease progression or intolerance), lack standard treatment options, or are deemed
unsuitable for standard treatment by the investigator, or have refused standard
treatment.
2. Cohort-Expansion Phase: In addition to the above criteria, the following must also
be met:
- Cohort A: Patients with locally advanced or metastatic NSCLC harboring the
EGFR-L858R mutation who have experienced disease progression after
third-generation EGFR-TKI treatment and carry secondary EGFR mutations (such as
C797S, L718Q, G724S, S768I, etc.).
- Cohort B: Patients with locally advanced or metastatic NSCLC harboring the
EGFR-L858R mutation who have failed standard treatment or are unsuitable for or
have refused standard treatment (patients with secondary EGFR mutations are
prioritized for Cohort A).
3. • Dose-Escalation Phase requires evaluable lesions, while Dose-Expansion and
Cohort-Expansion Phases require measurable lesions as defined by RECIST V1.1.
4. • Age ≥18 years, no gender restrictions.
5. • Expected survival ≥12 weeks.
6. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. • Adequate organ function, meeting the following criteria:
- Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/mm³), platelets
≥100 × 10⁹/L, hemoglobin ≥9 g/dL (90 g/L) without transfusion or hematopoietic
growth factors within 14 days prior to screening.
- Coagulation: International normalized ratio (INR) and activated partial
thromboplastin time (APTT) ≤1.5 × the upper limit of normal (ULN).
- Liver: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5
× ULN, or ≤5.0 × ULN in the presence of liver metastases; total bilirubin
(TBIL) ≤1.5 × ULN, or ≤3.0 × ULN in the presence of liver metastases or known
Gilbert's syndrome (unconjugated hyperbilirubinemia).
- Kidney: Serum creatinine (Scr) ≤1.5 × ULN, or for patients with Scr >1.5 ×
ULN, creatinine clearance (Ccr) ≥50 mL/min (calculated using the
Cockcroft-Gault formula); urine protein ≤1+, or if ≥2+, 24-hour urine protein
quantification showing <1 g.
8. • Toxicity from prior anti-tumor treatments must have resolved to CTCAE grade ≤1
(except for toxicities that, in the investigator's judgment, are long-lasting
and non-recoverable but pose no safety risk and are ≤2 in grade).
9. • Patients must have been previously diagnosed with the EGFR-L858R mutation via
local testing. In the Dose-Escalation and Dose-Expansion Phases, patients who
progressed on prior EGFR-TKI treatment must provide the genetic mutation results
from their most recent EGFR-TKI treatment. For Cohort A patients, progression on
third-generation EGFR-TKI treatment must have confirmed the presence of secondary
EGFR mutations (e.g., C797S, L718Q, G724S, S768I) via tissue or blood tests.
10. • Patients must be willing to provide blood samples and optionally provide tissue
samples for exploratory biomarker research.
11. • Non-breastfeeding women of childbearing potential must have a negative serum or
urine pregnancy test within 7 days before starting study treatment, and all enrolled
patients must agree to use medically accepted contraception for 1 month prior to
treatment, during the entire treatment period, and for 3 months after completing
treatment.
12. • Signed informed consent form.
Exclusion Criteria:
1. Prior or ongoing treatment with EGFR-L858R-targeted PROTAC therapies.
2. Less than 5 half-lives or 4 weeks (whichever is shorter) since the last anti-tumor
treatment before the first dose of study drug; less than 6 weeks since the last
treatment with nitrosoureas or mitomycin C; less than 1 week since the last
anti-tumor herbal treatment.
3. Patients who underwent major surgery (as defined by the investigator) or experienced
significant trauma within 4 weeks before the first dose of study drug; patients who
received radiation therapy within 4 weeks prior to the first dose, except for
palliative radiation (e.g., for bone metastases to control pain) that is unlikely to
affect bone marrow function, which may allow inclusion 2 weeks post-radiation.
4. Patients with unstable central nervous system (CNS) metastases (those who have
received treatment for brain metastases, have stable brain lesions, and have
discontinued corticosteroids, anticonvulsants, or mannitol treatment for ≥2 weeks
before the first dose may be considered for inclusion); patients with leptomeningeal
metastases or spinal cord compression.
5. History of other primary malignancies within the past 3 years, except for
malignancies that have been treated curatively with no known active disease and a
low risk of recurrence, or adequately treated non-melanoma skin cancers, cervical
carcinoma in situ, or papillary thyroid carcinoma.
6. Clinically significant cardiovascular diseases, including but not limited to:
- a) Unstable angina, acute myocardial infarction, or New York Heart Association
(NYHA) class II-IV heart failure;
- b) Ventricular arrhythmias or conduction disorders requiring clinical
intervention (e.g., complete left bundle branch block, third-degree
atrioventricular [AV] block, or second-degree AV block);
- c) Uncontrolled atrial fibrillation or atrial flutter;
- d) Prolonged QTcF interval (resting mean QTcF >450 msec for men or >470
msec for women);
- e) Left ventricular ejection fraction (LVEF) <50% on echocardiography;
- f) Hypertension not controlled with medication.
7. • History of interstitial lung disease (ILD) or non-infectious pneumonitis.
8. • Adrenal insufficiency.
9. • Use of proton pump inhibitors, strong CYP3A4 inhibitors or inducers, or
P-glycoprotein inhibitors or inducers within 7 days before the first dose.
10. • History of chronic diarrhea or diseases causing chronic diarrhea, such as
Crohn's disease or irritable bowel syndrome, or any condition that might affect
drug absorption (e.g., continuous diarrhea >CTCAE grade 1 within 1 week prior to
the first dose).
11. • Known severe hypersensitivity to the study drug or any of its excipients.
12. • History of deep vein thrombosis, pulmonary embolism, or any other serious
thromboembolic events within 6 months before the first dose, except for
catheter-related or superficial venous thrombosis, or lacunar infarcts.
13. • Clinically significant gastrointestinal bleeding or hemoptysis within 3 months
before the first dose, or any other significant bleeding history (e.g., pulmonary
hemorrhage).
14. • Clinically significant third-space fluid accumulation (e.g., uncontrolled ascites,
pleural effusion, or pericardial effusion requiring repeated drainage).
15. • Receipt of autologous transplantation within 3 months or allogeneic organ or stem
cell transplantation within 6 months prior to the first dose.
16. • Active hepatitis B virus (HBV) infection (screening positive for HBsAg or
anti-HBc, and HBV DNA levels above the detection limit; patients with stable disease
for at least 4 weeks after antiviral therapy may be included), active hepatitis C
virus (HCV) infection (positive HCV antibodies and detectable HCV RNA), human
immunodeficiency virus (HIV) infection, or active syphilis infection.
17. • Active infection requiring systemic treatment within 1 week before the first dose.
18. • History of substance abuse or any condition that, in the investigator's
judgment, may interfere with study participation or assessment of study results, or
any unstable condition that may compromise patient safety or compliance.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
浙江省杭州市拱墅区半山东路1号的英文翻译为： No. 1 Banshan East Road, Gongshu District, Hangzhou, Zhejiang Province, China
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Start date:
December 13, 2024
Completion date:
April 3, 2026
Lead sponsor:
Agency:
Betta Pharmaceuticals Co., Ltd.
Agency class:
Industry
Source:
Betta Pharmaceuticals Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06641609
