NSCLC (Advanced Non-small Cell Lung Cancer)
Conditions
Brief summary
This clinical trial consists of two parts: phase 2 and phase 3. The goal of phase 2 of this clinical trial is to compare which dose level of AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype non-small cell lung cancer (NSCLC) in adults. It will also learn about the safety of AMT-116. The main questions it aims to answer are: * Which level of AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype NSCLC? * What medical problems do participants have when taking AMT-116? The goal of phase 3 of this clinical trial is to compare AMT-116 to study doctor's choice (a kind of retainable treatment for you in the opinion of the study doctor) to see if AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype NSCLC. In both parts of this trial, participants will receive AMT-116 or study doctor's choice every 2 weeks until the study doctor thinks you are benefiting from your participation or until your disease progresses or you are unable to tolerate the study drug
Interventions
DRUGAMT-116
AMT-116 will be administered at 4 mg/kg or 5 mg/kg as an intravenous (IV) infusion on Day 1 of each 2-week cycle.
DRUGInvestigator's choice regimens (docetaxel or docetaxel plus ramucirumab)
Docetaxel will be administered as an IV infusion of 75 mg/m2 over approximately 60 minutes on Day 1 of each 3-week cycle. Ramucirumab will be administered as an IV infusion of 10 mg/kg over 30-60 minutes on Day 1 of each 3-week cycle prior to docetaxel
Sponsors
Multitude Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily agree to join this clinical trial, sign the informed consent form, and follow all trial arrangements, including scheduled hospital visits, examinations and other study requirements. 2. Age between 18 and 80 years old (including 18 and 80 years old) at the time of signing the informed consent form. 3. Diagnosed with non-squamous non-small cell lung cancer (NSCLC) confirmed by pathological or cytological tests. The disease must be either locally advanced and unresectable (not suitable for radical chemoradiotherapy) or metastatic advanced lung cancer. 4. Must have a clear EGFR gene test result before enrollment. Patients with other actionable gene mutations (excluding EGFR mutation) are eligible. Testing for other genes is not mandatory, and can be performed according to local hospital routine standards and available treatment options. 5. Have received no more than one line of chemotherapy for advanced or metastatic lung cancer. Neoadjuvant or adjuvant chemotherapy will be counted as one prior chemotherapy line if the disease progresses within 6 months after the end of treatment. 6. Have received at least one prior formal treatment (chemotherapy, targeted therapy or immunotherapy) for advanced or metastatic lung cancer, with subsequent disease progression or recurrence. Participants must meet the corresponding requirements based on their genetic status: 6.1 Patients without any actionable gene mutations: Have experienced disease progression after platinum-based chemotherapy and immune checkpoint inhibitor therapy (used alone or combined with chemotherapy), or are not suitable for the above two treatments clinically. 6.2 Patients with gene mutations that do not routinely use immunotherapy (e.g., ALK fusion): Have experienced disease progression after targeted therapy for gene mutations and platinum-based chemotherapy, or are not suitable for the above two treatments clinically. 6.3 Patients with gene mutations for which immunotherapy is a conventional treatment: Have also experienced disease progression after immune checkpoint inhibitor therapy (used alone or combined with chemotherapy), or are not suitable for immunotherapy clinically. 7. The investigator confirms that the patient is suitable for docetaxel treatment (only applicable for Phase 3 trial). 8. Have at least one measurable tumor lesion assessed by RECIST 1.1 criteria. 9. ECOG physical status score is 0 or 1, with normal daily physical activity. 10. Expected survival time is at least 12 weeks. 11. Have normal and stable organ function. No blood transfusion, erythropoietin, thrombopoietin, granulocyte colony-stimulating factor or other supportive treatment within 14 days before the test, and meet the following laboratory standards: * Blood routine: Absolute neutrophil count ≥ 1.5 × 10/L; platelet count ≥ 100 × 10/L; hemoglobin ≥ 90 g/L * Renal function: Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula) * Liver function: Total bilirubin ≤ 1.5 times the upper limit of normal (or ≤ 3 times the upper limit of normal for patients with Gilbert's disease); AST and ALT ≤ 2.5 times the upper limit of normal (or ≤ 5 times the upper limit of normal for patients with liver metastases) * Coagulation function: INR or aPTT ≤ 1.5 times the upper limit of normal for patients not receiving anticoagulant treatment 12. Female patients of childbearing age must use two effective contraceptive methods during the trial treatment period and within 12 weeks after the last dose of trial drug. A negative serum pregnancy test is required within 7 days before enrollment. Postmenopausal women (no menstruation for 12 consecutive months) or surgically sterilized women are exempted. 13. Male patients must use latex condoms during treatment and within 12 weeks after the last dose of trial drug (even after vasectomy). All patients are prohibited from donating sperm (male) or eggs (female) during the trial and within 12 weeks after the last drug dose.
Exclusion criteria
* I. General
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Adverse Events as Assessed by CTCAE v6.0 | About 7 months |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) | About 6 months |
| Progression free survival (PFS) | About 6 months |
| Duration of response (DOR) | About 6 months |
| Disease control rate (DCR) | About 6 months |
| Peak and pre-dose trough concentrations (Cmax and Ctrough) over time for conjugated antibody | About 6 months |
| Peak and pre-dose trough concentrations (Cmax and Ctrough) over time for total antibody | About 6 months |
| Peak and pre-dose trough concentrations (Cmax and Ctrough) over time for released free payload | About 6 months |
| Peak and pre-dose trough concentrations (Cmax and Ctrough) over time for the anti-drug antibodies (ADAs) | About 6 months |
| Overall survival | About 12 months |
Countries
Australia, United States
Contacts
CONTACTYanhong Fu
Outcome results
None listed