Unresectable, locally advanced, Stage III non-small cell lung cancer (NSCLC) MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Cisplatino
Product Name: Cisplatino
Product Code: [-]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATINO
CAS Number: 15663-27-1
Current Sponsor code
Sponsors
MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has pathologically confirmed diagnosis of NSCLC 2. Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8 3. Is determined to have unresectable, Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon 4. Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body FDGPET or FDG-PET/CT and CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain 5. Has measurable disease as defined by RECIST 1.1, with at least 1 lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review 6. Has not received prior treatment for their Stage III NSCLC 7. Has provided tumor tissue sample. FFPE blocks are preferred to slides 8. Has an ECOG Performance Status of 0 or 1 assessed within 7 days prior to the first administration of study intervention 9. Has a life expectancy of at least 6 months 10. Has adequate PFT defined as a FEV1 >50% of predicted normal volume and the carbon monoxide lung diffusing capacity (DLCO) >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) is determined to be =90% on room air 11. Is male or female, at least 18 years of age inclusive, at the time of providing informed consent 12. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Chemotherapy platinum doublet: 95 days - Radiotherapy: 90 days • Refrain from donating sperm PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed For more inclusion criteria please refer to the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 392 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 392
Exclusion criteria
Exclusion criteria: 1. Has SCLC or tumors with the presence of small cell elements. Mixed squamous/nonsquamous tumors are eligible 2. Is likely to have a radiation treatment plan that will encompass a volume of whole lung (total lung-GTV) receiving =20 Gy in total (lung V20) of more than 34% of whole lung volume 3. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer 4. Has received prior therapy with an anti-TIGIT, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg,CTLA-4, OX-40, CD137) 5. Has received major surgery (with the exception of replacement of vascular access) within 4 weeks before randomization 6. Is expected to require any other form of antineoplastic therapy, while on study 7. Has received colony-stimulating factors (e.g., G-CSF, GM-CSF, or recombinant erythropoietin) within 28 days prior to the first dose of study intervention 8. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed Pemetrexed-specific Criteria 9. Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose =1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed 10. Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone 11. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention 12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication 13. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years 14. Has severe hypersensitivity (= Grade 3) to MK-7684A, platinum doublet components, durvalumab and/or any of its excipients 15. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) 16. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 17. Has an active infection requiring systemic therapy 18. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority 19. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection 20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator For more inclusion criteria please refer to the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare PFS per RECIST 1.1 as assessed by BICR. 2. To compare OS.;Secondary Objective: 1. To compare MK-7684A with cCRT followed by MK-7684A to cCRT followed by durvalumab with respect to ORR per RECIST 1.1 as assessed by BICR in participants with TPS =1% and PD-LI. 2. To evaluate the safety and tolerability of MK-7684A with cCRT followed by MK-7684A compared to cCRT followed by durvalumab. 3. To compare MK-7684A with cCRT followed by MK-7684A to cCRT followed by durvalumab with respect to DOR per RECIST 1.1 as assessed by BICR in participants with TPS =1% and PD-LI. 4. To evaluate the change from baseline in GHS/QoL, cough, chest pain, dyspnea and physical functioning following treatment with MK-7684A with cCRT followed by MK-7684A compared to cCRT followed by durvalumab in participants with TPS =1% & PD-L1. 5. To evaluate the TTD in GHS/QoL, cough, chest pain, dyspnea and physical functioning following treatment with MK-7684A with cCRT followed by MK-7684A compared to cCRT followed by durvalumab in participants with TPS =1% & PD-L1.;Primary end point(s): 1. Progression Free Survival (PFS) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) 2. Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1. Up to ~57 months 2. Up to ~6 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate (ORR) per RECIST 1.1 as assessed by BICR 2. Number of participants with one or more adverse events (AEs) 3. Number of participants that discontinued study intervention due to AEs 4. Duration of response (DOR) per RECIST 1.1 as assessed by BICR 5. Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) Core 30 (C30) items 29 and 30, Global Health Score/Quality of Life (GHS/QOL) 6. Change from baseline in EORTC QLQ-Lung cancer 13 (LC13) item 1, cough 7. Change from baseline in EORTC QLQ-LC13 item 10, chest pain 8. Change from baseline in EORTC QLQ C30 item 8, dyspnea 9. Change from baseline in EORTC QLQ C30 items 1-5, physical functioning 10. Time-to-true deterioration (TTD) in EORTC QLQ C30 items 29 and 30, GHS/QOL 11. TTD in EORTC QLQ-LC13 item 1, cough 12. TTD in EORTC QLQ-LC13 item 10, chest pain 13. TTD in EORTC QLQ C30 item 8, dyspnea 14. TTD in EORTC QLQ C30 items 1-5, physical functioning;Timepoint(s) of evaluation of this end point: 1. Up to ~57 months 2. Up to ~18 months 3. Up to ~15 months 4. Up to ~57 months 5. Baseline and up to ~15 months 6. Baseline and up to ~15 months 7. Baseline and up to ~15 months 8. Baseline and up to ~15 months 9. Baseline and up to ~15 months 10. Up to ~15 months 11. Up to ~15 months 12. Up to ~15 months 13. Up to ~15 months 14. Up to ~15 months | — |
Countries
Australia, Brazil, Chile, China, Costa Rica, Germany, Greece, Guatemala, Israel, Italy, Japan, Korea, Republic of, Mexico, Portugal, Romania, Russian Federation, Spain, Turkey, Ukraine, United States
Contacts
Public ContactDivisione Ricerca Clinica
MSD Italia S.r.l.
Outcome results
None listed