Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation

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:
• •* 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.