Trial Title:
Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation
NCT ID:
NCT06015568
Condition:
Non-Small Cell Lung Cancer、EGFR Sensitive Mutation
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Hypersensitivity
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MCLA-129: 1500mg or 2000mg IV Q2W
Description:
Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor
treatment, loss of follow-up, or voluntary withdrawal occurs
Arm group label:
MCLA-129+ Befotertinib
Intervention type:
Drug
Intervention name:
Befotertinib: 75 mg or 100 mg Po QD
Description:
The initial dose of Befotertinib is 75 mg orally once daily (QD) for one cycle, and then
increased to 100 mg orally QD in the absence of CTCAE grade ≥ 2 headache or
thrombocytopenia during the first cycle, otherwise maintained to 75 mg orally QD.
Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor
treatment, loss of follow-up, or voluntary withdrawal occurs.
Arm group label:
MCLA-129+ Befotertinib
Summary:
To evaluate the safety and tolerance of MCLA-129 combined with Befotertinib in patients
with advanced non-small cell lung cancer with EGFR-sensitive mutations.
Detailed description:
This is a phase I study to evaluate the safety, pharmacokinetic characteristics and
antitumor activity of anti-EGFR/c-Met bispecific antibody MCLA-129(1500mg Q2W IV or
2000mg Q2W IV) combined with Befotertinib (75 mg once daily for first cycle, then
increased to 100 mg once daily, orally) in Patients of advanced non-small cell lung
cancer with exon 19 deletion or exon 21 L858R mutation(either alone or in combination
with other EGFR mutations).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age from 18 to 75 years.
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC that
is not suitable for radical surgery or radiotherapy, and harbored EGFR exon 19
deletion or exon 21 L858R mutation( either alone or in combination with other EGFR
mutations) in NSCLC assessed by genetic testing.
- For Part 1: patients with advanced NSCLC must be progression, or intolerance, or
rejected to standard therapy(subjects treated with Befotertinib must be progression
of the disease).
- For Part 2, each cohort is defined as follows:
- Cohort A: Previously diagnosed EGFR-sensitive mutations and no systemic
antitumor therapy for locally advanced or metastatic NSCLC.
- Cohort B: Advanced NSCLC patients with previously diagnosed EGFR-sensitive
mutations and third generation EGFR-TKI resistance.
- Cohort C: Advanced NSCLC patients who had previously been diagnosed with
EGFR-sensitive mutations and first or second EGFR-TKI resistance.
Patients in cohorts B and C must also resistance, or intolerance, or rejection of
platinum-containing chemotherapy.
•Patients of the dose escalation phase in Part 1 must have evaluable diseases, and others
must have measurable diseases as defined in RECIST V1.1 definition.
Note: The selected target lesions must meet one of two criteria: 1) no previous local
treatment or 2) subsequent progression within the previous local treatment area as
determined by RECIST V1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status scores are 0-1.
- Expected survival is ≥3 months.
- With certain organ system functions (without transfusion, use of blood components,
or G-CSF support within 14 days before testing), as defined below:
oAbsolute neutrophil count (ANC)≥1.5×10^9/L oPlatelet count (PLT)≥100×10^9/L oHemoglobin
(HB)≥10 g/dL oSerum albumin≥30 g/L oTotal bilirubin≤1.5 times the upper limit of normal
(ULN) oAlanine amino transferase ( ALT) and aspartate amino transferase (AST) ≤3×ULN
oCreatinine≤1.5×ULN.If creatinine is>1.5×ULN, creatinine clearance is≥50 mL/min as
calculated by Cockcroft-Gault formula, or urinary creatinine clearance≥50 mL/min within
24 hours as measured, the patients can still be enrolled.
- Willing and able to follow the trial and follow-up procedures.
- Capable of understanding the trial nature and voluntarily signing the written
informed consent form.
Exclusion Criteria:
- Use of certain investigational drug or antineoplastic agent within 14 days or 5 half
lives (whichever is longer) before first administration of investigational drug (For
drugs with a longer half-life, a maximum of 4 weeks is required from the last
administration; 6 weeks for chemotherapy with delayed toxicity, such as Nitroso urea
or Mitomycin C).
- Execution of large surgery and radiotherapy (except focal palliative radiotherapy at
least 2 weeks before first administration) within 4 weeks before first
administration.
- For the dose extension stage of part 2 and part 2: having previously received
systemic anti-tumor therapy exceeding three lines (excluding maintenance therapy).
- Previously received EGFR/c-Met bispecific antibody drugs (such as JNJ-61186372,
EMB-01, or GB263T) for treatment.
- Prior to the first administration of the study drug, previous treatment-related
toxic reactions did not alleviate to level 1 or below (CTCAE 5.0 standard), except
for hair loss.
- With other malignant tumors in the past 3 years, except cancers that have been cured
significantly or can be focally cured, e.g. basosquamous carcinoma of skin,
carcinoma cervix in situ, or in situ breast carcinoma.
- Primary malignant tumor of the central nervous system, meningeal metastasis, or
brain metastasis with spinal cord compression, or risk of cerebral hemorrhage, or
symptomatic brain metastasis, or unstable brain metastasis requiring steroid and/or
dehydration to reduce intracranial pressure 2 weeks before enrollment (subjects with
brain metastases who are Asymptomatic or stable for more than 2 weeks after
treatment and do not need steroids and/or dehydration to reduce intracranial
pressure can be included in the group).
- With clinically significant cardiovascular disorder, including but not limited to:
- Arterial thromboembolism, deep vein thrombosis or lung embolism diagnosed
within 3 month before first administration of the investigational drug. Non-
obstructive catheter related clot and other clinically irrelevant thrombosis
are not included in the exclusion criteria. Patients with a history of related
thrombosis diagnosed 3 months ago must be clinically stable for at least 4
weeks before initial administration.
- With any of the following medical history within 6 months before first
administration of the investigational drug: myocardial infarction, unstable
angina, stroke, transient ischemic attack, coronary or peripheral artery
bypass, or any acute coronary syndrome.
- With abnormal ECG corrected QT interval (QTcF) at rest in the screening period.
Remeasurement is made twice at intervals of more than 5 minutes. For average
QTcF of 3 times ECG inspections: male: ≥ 450 msec, and female: ≥ 470 msec. With
clinically significant abnormal heart rate, conduction, and ECG form at rest,
e.g. complete left bundle branch block, third-degree conduction block,
second-degree conduction block, and PR interval > 250 msec, double law, triple
law, preexcitation syndrome, etc.
- Poorly controlled hypertension in the investigator's opinion (systolic blood
pressure > 180 mmHg, or diastolic blood pressure > 100 mmHg).
- New York Heart Association Grade III-IV congestive heart failure, or
hospitalization due to congestive heart failure within 6 months before first
administration of the investigational drug.
- Pericarditis/clinically significant pericardial effusion.
- Cardiomyopathy.
- ther clinically significant cardiovascular disordesr as believed by
investigators.
- Active hepatitis B (hepatitis B surface antigen (HBsAg) positive and serum HBV DNA
quantitative results higher than or equal to the detection limit), hepatitis C virus
antibody, HIV antibody and treponema pallidum antibody positive (subjects who have a
history of HCV and have completed antiviral treatment, and whose laboratory test
results show that HCV-RNA is below the lower limit of quantification, can be
selected for the study; those who test negative for syphilis titer can be selected).
- Patients with Interstitial lung disease, including drug-induced Interstitial lung
disease or radiation pneumonia requiring long-term use of steroids or other
Immunosuppressive drug in the past 1 year.
- Subjects with active gastrointestinal (GI) disease, or with a risk of GI
perforation, or with other diseases that significantly interfere with the
absorption, distribution, metabolism, or excretion of investigational drugs.
Including but not limited to: unable to take oral medicine, uncontrollable nausea or
vomiting, Bowel obstruction, inflammatory bowel disease or extensive intestinal
resection, etc.
- Current severe disease or medical condition, including but not limited to
uncontrolled active infection, uncontrollable pleural or abdominal effusion, and
clinically significant lung, metabolic or psychiatric disorders.
- Women with child bearing potential, pregnant women or lactating women with pregnancy
test positive 7 days before treatment, and male and female unwilling to take
effective contraception measures or having a birth plan during the treatment and
within 3 months after end of treatment.
- Subjects with a history of allergies or suspected allergic symptoms to the study
drug MCLA-129, Befotertinib, or any component of both study drugs (see the
investigator's brochure).
- Within one week before the first administration of the investigational drug, it is
currently in use or needs to be combined with CYP3A strong inhibitors or inducers
during the study period.
- Subjects still using Warfarin within 7 days before the first administration (low
molecular weight heparin sodium is allowed).
- Patients poorly compliant, unable or unwilling to follow the study and/or follow-up
procedures listed in the protocol, or unsuitable to participate in this trial in the
investigator's opinion.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The first affiliated hospital of bengbu medical college
Address:
City:
Bengbu
Country:
China
Contact:
Last name:
Wei Li, M.D.
Phone:
+86 13965282263
Email:
bbmcliwei@126.com
Contact backup:
Last name:
Yuanyuan Liu, Bachelor
Phone:
+86 18955225050
Email:
120952297@qq.com
Facility:
Name:
Hunan cancer hospital
Address:
City:
Changsha
Country:
China
Contact:
Last name:
Lin Wu, M.D.
Phone:
+86 13170419973
Email:
wulin-calf@vip.163.com
Facility:
Name:
Shanghai chest hospital
Address:
City:
Shanghai
Country:
China
Contact:
Last name:
Shun Lu, M.D.
Phone:
00-021-22200000-2153
Email:
Shun_lu@hotmail.com
Start date:
September 1, 2023
Completion date:
July 4, 2029
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/NCT06015568
