Subjects With Advanced Thoracic Tumors With Homozygous MTAP deletion
Conditions
Interventions
Experimental group:Carboplatin + pemetrexed + pembrolizumab or AMG 193 + carboplatin + pemetrexed + pembrolizumab or AMG 193 + pembrolizumab
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects have provided informed consent prior to initiation of any study-specific activities/procedures. 2. Age = 18 years old (or >= legal age if the legal age in your country is greater than 18 years). 3. Histologically or cytologically confirmed diagnosis of metastatic NSCLC and no prior systemic therapy for metastatic or unresectable disease, with the exception of 28-day first-line therapy as listed in the exclusion criteria below. Group A (AMG 193 + Carboplatin + Paclitaxel + Pembrolizumab): - Predominantly squamous cell histology. Group B (AMG 193 + carboplatin + pemetrexed + pembrolizumab): - Predominantly non-squamous histology. Arm C (AMG 193 + pembrolizumab): - Tumors are PD-L1 positive according to locally approved pembrolizumab monotherapy instructions (e.g., TPS >= 1% in the US, TPS >=50% in the EU); 4. Subject has homozygous MTAP deletion. 5. Archived tumor tissue or archived tissue blocks must be provided. 6. Able to swallow and maintain oral study treatment and willing to document compliance with daily trial drug administration. 7. Disease as measurable as defined by Efficacy Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by the investigator of the study center. 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment. 9. Local laboratory test results showing good hematopoietic function, defined as: Absolute neutrophil count = 1.5 x 109/L • Platelet count >= 100 x 109/L • Hemoglobin > 9 g/dL; 10. Local laboratory findings showing good renal function, defined as: Estimated creatinine clearance based on the Modified Diet for Kidney Disease formula or based on the Cockcroft-Gault formula, estimated GFR >=50 mL/min (Group A only: >= 60 mL/min). 11. Good liver function with local laboratory test results, defined as: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 g/dL; 12. Good coagulation, defined as: Prothrombin time or activated partial thromboplastin time < 1.5 x ULN with an international normalized ratio (INR) of < 1.5 x ULN, or within the therapeutic range if receiving prophylactic anticoagulation. 13. Good cardiac function, defined as: 350 msec < baseline QTc interval <=470 msec (based on the average of ECG values in triplicate during the screening phase). 14. Thyroid-stimulating hormone (TSH) levels within the normal range of the local laboratory. 15. The minimum life expectancy is 12 weeks, as judged by the investigator.
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy for metastatic NSCLC. 2. Has undergone major surgery within 28 days prior to the first dose of AMG 193 administration. Note: Subjects who have surgically obtained biopsies for diagnosing disease are allowed to participate in this study. 3. Prior treatment with MAT2A inhibitors or PRMT5 inhibitors. 4. Toxicities from prior antineoplastic therapy that have not improved to at least Grade 1 on Common Adverse Event Evaluation Criteria (CTCAE) version 5.0, with the exception of alopecia or stable and well-controlled toxicities. 5. Subjects with Grade 2 or above immune-mediated adverse events (irAEs), including adverse events leading to permanent discontinuation of immuno-oncology agents. - Exception: hypothyroidism. 6. Prior treatment with > 25% bone marrow radiotherapy. 7. Radiotherapy within 28 days prior to the first dose (or focal or focal palliative radiotherapy within 14 days prior to the first dose). All radiotherapy-related toxicities must have improved to 2 cm in size. 14. Subjects with leptomeningeal disease are excluded with or without symptoms, even if treated. 15. Poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once a month. Subjects who have been implanted with a PleurX catheter may be considered for participation in this study with the approval of the medical monitor. 16. History of other malignancies within the past 3 years, with the following exceptions: Malignancy treated curatively, no known active disease within >= 2 years prior to enrollment and low risk of recurrence in the opinion of the treating physician. Non-melanomatous skin cancer or lentigo maligna has been adequately treated and currently shows no evidence of disease. Cervical cancer in situ has been adequately treated and no evidence of disease is currently shown. Ductal carcinoma in situ of the breast has been adequately treated and no evidence of disease is currently shown. Prostatic intraepithelial neoplasia has been adequately treated and currently shows no evidence of disease. Noninvasive papillary urothelial carcinoma or carcinoma in situ has been adequately treated. 17. Current presence of any evidence of interstitial lung disease or lung inflammation, or prior history of interstitial lung disease or non-infectious lung inflammation. 18. Active infection requiring systemic therapy. 19. Presence of evidence of active SARS-COV2 infection. If there is a known or suspected recent confirmed infection SARSCOV2, at least 10 days (if any) must have elapsed since the onset of symptoms. 20. History of arterial thrombosis (e.g.,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities (DLTs);Adverse events during the treatment period;Serious adverse events as well as vital signs;Electrocardiogram (ECG);Changes in clinical laboratory tests; | — |
Countries
China
Contacts
Public ContactJinji Yang
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed