Clinical trial NCT06341660: To Evaluate the Safety and Tolerability of Carbognilumab Combined With Chemotherapy as the First-line Treatment for Patients With KEAP1 Mutated Advanced or Postoperative Recurrent Non-small Cell Lung Cancer (NSCLC)
Official title: A Single-arm Pilot Study of Patients With Advanced or Postoperative Recurrent Non-small Cell Lung Cancer (NSCLC) With KEAP1 Mutation Treated With Carbonizumab Combined With Chemotherapy as the First-line Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of carbognilumab combined with chemotherapy as first-line treatment in patients with KeAP1-mutated advanced or postoperative recurrent non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

1. voluntary participation in clinical research; Fully understand and Informed the study and sign the Informed Consent Form (ICF); Be willing to follow and be able to complete all trial procedures.
2. Age ≥18 years old and ≤75 years old when signing ICF.
3. histologically or cytologically confirmed advanced or postoperative recurrent non-small cell lung cancer (AJCC 8th edition).
4. STK11 mutations were detected by NGS, and no other sensitive mutations could be targeted therapy (including EGFR, ALK, ROS1, RET, c-Met, HER2, BRAF gene rearrangement, fusion, amplification, and skipping).
5. The patient had not received systemic antitumor therapy.
6. Patients who had received one prior chemotherapy regimen were allowed, regardless of whether chemotherapy was administered before, after, or concurrently with targeted therapy.
7. Patients receiving adjuvant or neoadjuvant therapy were allowed if adjuvant/neoadjuvant therapy had been completed at least 12 months before diagnosis of advanced or postoperative recurrent NSCLC.
8. The interval between the end of previous nonsystemic antitumor therapy and the start of study medication had to be 4 weeks or more. Treatment-related AE recovered to CTCAE 4.03≤ grade 1 (except grade 2 alopecia).
9. have at least one measurable target lesion as assessed by the investigator according to iRECIST requirements within 4 weeks before enrollment.
10. If available, patients can provide eligible tumor tissue for PD-L1 expression level measurement.
11. an ECOG PS score of 0 or 1 within 7 days before the first dose of study medication.
12. predicted survival time ≥12 weeks (3 months).
13. had good major organ function, defined as meeting the following criteria, and had not received blood transfusions, albumin, recombinant human thrombopoietin, or colony-stimulating factor (CSF) within 14 days before the first dose of study medication.
14. Female patients must meet one of the following conditions:

(1)menopause, defined as absence of menses for at least 1 year and no confirmed cause other than menopause, or (2) having undergone sterilization (removal of ovaries and/or uterus) 3) be fertile, provided that: Patients had to have a negative serum pregnancy test within 7 days before randomization and agree to use contraception with an annual failure rate of \<1% or to abstain from heterosexual intercourse for at least 120 days from the date of written informed consent until the last dose of trial drug was administered. At least 150 days after the last dose of chemotherapy) (contraceptive methods with an annual failure rate of \<1% include bilateral tubal ligation, male sterilization, proper use of ovulation-suppressing hormonal contraceptives, hormone-releasing intrauterine devices, and copper intrauterine devices or condoms), and Do not breastfeed.

15.Male patients had to agree to either abstain from sex (avoid heterosexual intercourse) or to use contraception, as specified by either abstinence or use of condoms to prevent exposure of the drug to the embryo during chemotherapy (paclitaxel/pemetrexed/carboplatin) for the duration of treatment with a woman of reproductive age or a pregnant partner and for at least 150 days after the last dose of chemotherapy. Regular abstinence (e.g., calendar day, ovulation, basal body temperature, or postovulatory methods of contraception) and in vitro ejaculation are ineligible methods of contraception.

Exclusion Criteria:

1. received systemic therapy for advanced NSCLC within 4 weeks after enrollment;
2. the subjects had a history or concurrent history of other malignant tumors (except 3.cured basal cell carcinoma of the skin and carcinoma in situ of the cervix).

candidates for or prior recipients of organ or bone marrow transplantation. 4.uncontrollable pleural, pericardial, or ascites with appropriate interventions.

5.subjects with clinically symptomatic CNS metastases (e.g., brain edema, need for hormonal intervention, or progression of brain metastases). Patients who had received previous treatment for brain or meningeal metastases were eligible if they had been clinically stable (on MRI) for at least 2 months and had stopped systemic hormone therapy (at a dose of \>10mg per day of prednisone or other iso-efficacy hormones) for more than 2 weeks.

6.spinal cord compression that cannot be cured by surgery and/or radiotherapy. 7. have a history of hemoptysis (\> 50ml/day) within 3 months before screening; Or clinically significant bleeding symptoms or a definite tendency to bleed.

8. received definitive thoracic radiotherapy within 28 days before enrollment; Subjects who received palliative radiotherapy to a bone lesion outside the chest within 2 weeks before receiving the first dose of study drug.

9. severe unhealed wound ulcers or fractures, or major surgery within 28 days before randomization or expected to undergo major surgery during the study period.

10.Any unstable systemic disease: These included, but were not limited to, active pulmonary tuberculosis, active infection, unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months before screening), myocardial infarction (within 6 months before screening), and congestive heart failure (New York Heart Association \[NYHA\] class ≥ 2 Grade II), severe cardiac arrhythmias requiring medical therapy, and hepatic, renal, or metabolic disorders 11. poorly controlled hypertension (defined as systolic blood pressure (BP) ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) with a history of hypertensive crisis or hypertensive encephalopathy.

12. clinically significant hemoptysis (\> 50ml/day) within 3 months before enrollment; Or clinically significant bleeding symptoms or a clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ or above, or large vessel vasculitis; Arterial/venous thrombotic events occurred within 12 months before enrollment, such as cerebrovascular accident, deep vein thrombosis, and pulmonary embolism.

13. patients with CTCAE 4.03 peripheral neuropathy grade ≥2.

Primary outcomes:
measure: Safety assessments and ORR
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Guangdong
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangzhou
Study officials:
References: