Clinical trial NCT06391008: Immunosensitized Radiotherapy Combined With Evoximab (AK112) and Chemotherapy Neoadjuvant Therapy for Stage II-III Non-small Cell Lung Cancer
Official title: Immunosensitized Radiotherapy Combined With Evoximab (AK112) and Chemotherapy Neoadjuvant Therapy for Stage II-III Non-small Cell Lung Cancer: a Single Arm, Open Label, Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Stereotactic Radiotherapy; Evoximab (AK112); New Adjuvant Therapy for Non-small Cell Lung Cancer
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, prospective, single center Phase II clinical study. Intended to evaluate the main pathological response rate (MPR) and safety of stereotactic immunosensitized radiotherapy combined with Evoximab (PD-1/VEGF-A bispecific antibody) and chemotherapy neoadjuvant therapy for stage II-III NSCLC. Simultaneously observe and evaluate the complete pathological response rate (pCR), R0 resection rate, and event free survival (EFS) of stage II-III NSCLC treated with stereotactic radiotherapy combined with Evoximab (PD-1/VEGF-A bispecific antibody) and chemotherapy. Exploratory analysis based on serum/tumor molecular biological markers, as well as the optimal response time and mechanism for combined response.


Eligibility criteria: Inclusion Criteria:

1. The patient voluntarily joined this study and signed an informed consent form;
2. ≥ 18 years old, both male and female are eligible;
3. Pathologically confirmed stage II-III NSCLC (AJCC 8th)
4. NSCLC confirmed by histology or cytology; No known EGFR/ALK gene mutations
5. ECOG score: 0-1;
6. Expected survival time ≥ 12 weeks;
7. The functions of important organs meet the following requirements:

   Absolute neutrophil count ≥ 1.5 × 10 \^ 9/L; Absolute lymphocyte count ≥ 0.8 × 10 \^ 9/L; Platelets ≥ 80 × 10 \^ 9/L; Hemoglobin ≥ 90g/L; Bilirubin ≤ 1.5 × ULN (within 7 days before the first medication); ALT and AST ≤ 1.5 × ULN (within 7 days before the first medication); Serum creatinine ≤ 1.5 × ULN;
8. Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously, and if FT3 and FT4 levels are normal, they can be included in the study);
9. Non surgical sterilization or female patients of childbearing age are required to use a medically recognized contraceptive measure (such as an intrauterine device, contraceptive pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Non surgically sterilized female patients of childbearing age must have a negative serum or urine HCG test within 72 hours prior to enrollment in the study; And it must be non lactation period; For male patients whose partners are women of childbearing age, effective methods of contraception should be used during the trial period and within 3 months after the last treatment medication.
10. Agree to provide blood samples and histological specimens. -

Exclusion Criteria:

1. The patient has any active autoimmune diseases or a history of autoimmune diseases (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism; the patient has vitiligo; asthma that has completely relieved in childhood and does not require any intervention in adulthood can be included; asthma that requires medical intervention with bronchodilators cannot be included);
2. The patient is currently using immunosuppressive agents or systemic hormone therapy to achieve immunosuppressive effects (dosage\>10mg/day prednisone or other therapeutic hormones), and continues to use them within 2 weeks prior to enrollment;
3. Has experienced severe allergic reactions to other monoclonal antibodies;
4. Suffering from hypertension and unable to achieve good control through antihypertensive drug treatment (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg);
5. There are clinical symptoms or diseases of the heart that cannot be well controlled, such as:

   NYHA grade 2 or above heart failure; Unstable angina pectoris; Have experienced myocardial infarction within one year; Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; QTc\>450ms (male); QTc\>470ms (female);
6. Abnormal coagulation function (INR\>2.0, PT\>16s), with a tendency to bleed or undergoing thrombolysis or anticoagulation treatment, allowing prophylactic use of low-dose aspirin and low molecular weight heparin;
7. Received previous anti-tumor immunotherapy, chemotherapy, and anti-tumor vaccine treatment (excluding adjuvant chemotherapy, if receiving adjuvant chemotherapy, disease recurrence or metastasis occurs more than 6 months after the last chemotherapy).
8. The patient has active infection, unexplained fever ≥ 38.5 ° C within 7 days before medication, or baseline white blood cell count\>15 × 109/L; Individuals with purulent and chronic infections, and wounds that persist and do not heal;
9. Patients with bone metastases who have received palliative radiotherapy within the 4 weeks prior to participating in this study have a bone marrow area greater than 5%;
10. The patient has previously received anti PD-1, anti PD-L1, and anti PD-L2 treatments;
11. Individuals who are known to be allergic to the components of recombinant humanized anti-PD-1 monoclonal antibody drugs and vaccines;
12. Pregnant or lactating women, or female patients who have fertility but have not taken contraceptive measures;
13. Other malignant tumors (excluding basal cell or squamous cell carcinoma, superficial bladder cancer cancer, cervical carcinoma in situ or breast cancer) in the past 5 years;
14. Patients participating in other clinical trials simultaneously

Primary outcomes:
measure: Major Pathological Response (MPR) Rate
timeFrame: Up to 6 months
measure: Safety and tolerability
timeFrame: Up to 6 months
Secondary outcomes:
measure: Pathological complete response (pCR)
timeFrame: Up to 6 months
measure: EFS
timeFrame: Up to 6 months
Other outcomes:
measure: Exploratory purposes
timeFrame: Up to 6 months
Locations:
Study officials:
References: