NSCLC
Conditions
Interventions
Cohort 1:tuvonralimab/iparomlimab combined with chemotherapy
Cohort2:tuvonralimab/iparomlimab combined with chemotherapy
Sponsors
Cancer Hospital, Chinese academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age =18 years, no gender restrictions; 2. Histologically or cytologically confirmed, unresectable or metastatic lung adenocarcinoma patients harbouring non-canonical epidermal growth factor receptor (EGFR) mutations (e.g., exon 20 insertion, S768I, L861Q, G719X, or composite mutations); 3. Expected survival =3 months; normal hepatic, renal, pulmonary, and cardiac function; 4. ECOG performance status: 0–2; 5. At least one measurable radiographic lesion with definite progression according to RECIST v1.1 following prior therapy; 6. Prior treatment with =2 lines of therapy; Cohort 1: Patients with Exon20ins mutation: Patients who progressed after prior standard first-line chemotherapy or combination anti-angiogenic inhibitor therapy. For participants ineligible for platinum-based therapy, prior alternative treatments (e.g., investigational or approved EGFR20 large-molecule monoclonal antibodies) are permissible. ? After resistance to Exon 20-targeted tyrosine kinase inhibitors [TKIs]. ? Patients who progressed on first-line chemotherapy or combination anti-angiogenic therapy, EGFR Exon 20 large-molecule monoclonal antibodies, etc., or who experienced intolerance or progression after second-line treatment with TKIs such as suvotitinib or ADC agents. Cohort 2: Patients harbouring EGFR S768I, L861Q, G719X or other mutations/compound mutations: ? Sensitive to EGFR TKIs and progressed after prior first-line EGFR TKI therapy. ? Progressed after prior second-line chemotherapy or combination therapy with anti-angiogenic agents or ADCs. 7. Sufficient organ function prior to first dose study treatment (no infusion of blood components or leukocyte/platelet growth-stimulating agents permitted within 7 days before obtaining laboratory results). (1) White blood cell count (WBC) = 3 × 10^9/L; (2) Absolute neutrophil count = 1.5 × 10^9/L; (3) Platelet count = 100 × 10?/L; (4) Haemoglobin = 90 g/L; (5) Serum creatinine = 1.5 × ULN or creatinine clearance (CLcr) = 50 mL/min, calculated using the Cockcroft-Gault formula; (6) Total bilirubin = 1.5 × ULN (patients with Gilbert's syndrome permitted 50%. 8. Not having participated in any clinical trials within the preceding 4 weeks; 9. Expected to demonstrate good compliance, capable of attending follow-up appointments as per protocol requirements to monitor efficacy and adverse reactions; 10. The subject is able to understand the nature of this study and voluntarily signs the informed consent form.
Exclusion criteria
Exclusion criteria: 1.Symptomatic central nervous system metastases. Subjects may be included if they meet the following conditions at least 2 weeks prior to the first dose of study treatment: CNS metastases are appropriately treated and neurological symptoms (in addition to residual signs and symptoms related to CNS treatment) are resolved, and the dose of systemic corticosteroids is discontinued or reduced ( 10 mg prednisone daily or equivalent) or other immunosuppressive drugs (such as cyclophosphamide, azathioprine, methotrexate, response stop, TNF-alpha inhibitors, etc.) within 2 weeks prior to starting study treatment. Topical corticosteroids, nasal sprays, and inhaled steroids are permitted. Systemic corticosteroids to prevent contrast allergy are allowed. low-dose corticosteroids for orthostatic hypotension are allowed 5.Intercurrent illness that may seriously endanger patient safety or affect study completion as determined by the investigator, such as hypertension (systolic blood pressure >=160mmHg and/or diastolic blood pressure >=100mmHg) that cannot be controlled by 2 or more antihypertensive medications and severe diabetes 6.Patients with the following cardiovascular diseases will be excluded: (1) Patients with acute myocardial infarction or New York Heart Association (NYHA) class III or IV heart failure within 6 months prior to starting study treatment. (2) Cardiovascular disease that is not well controlled prior to the first cycle of study treatment, including angina, pulmonary hypertension, or severe arrhythmias or conduction disturbances. (3) Lead ECG showing a mean QT interval (QTcF) of >450 ms (males) or >470 ms (females) prior to study treatment. 7.Patients with prior or current interstitial lung disease, pneumoconiosis, radiation pneumonitis, or severe pulmonary impairment that may interfere with the detection and treatment of suspected treatment-related pulmonary toxicity in the opinion of the investigator 8.Intestinal fistula, gastrointestinal perforation, or abdominal abscess within 6 months prior to screening 9.Uncontrolled pleural and abdominal effusion, or pericardial effusion requiring repeated drainage (>= 1 time per month) 10.Uncontrolled or symptomatic hypercalcemia 11.Have grade >=2 peripheral neuropathy (CTCAE v5.0) before study treatment 12.Previous immunotherapy, including immune checkpoint inhibitor antibodies (anti-PD-1, PD-L1, CTLA-4 antibodies, etc.), agonist antibodies (anti-ICOS, CD40, CD137, GITR, OX40, etc.), immune cell therapy, etc. 13.Severe bleeding tendency or coagulation dysfunction, or currently receiving anticoagulant therapy or thrombolytic therapy. Imaging shows signs of tumor invasion of large blood vessels [the tumor is completely close to, surrounded, or invaded by a chamber of the large vessel (eg, pulmonary artery or large vessel)]. Two or more hemoptysis (0.5 teaspoons (2.5 mL) >= each time) within 3 months prior to screening Thrombosis within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| mPFS;mOS;mDOR; | — |
Countries
China
Contacts
Public ContactHaiyan Xu
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed