D022 Bronchus and lung Bronchus and lung
Conditions
Interventions
Pembrolizumab 25mg/ml 200mg will be administered by IV infusion over 30 minutes on day 1 of each 3-week cycle for 4 doses. Cisplatin IV 75mg/m2. 75mg/m2 will be administered as an IV infusion over 60
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics. Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods: Criteria 1. Has histological confirmation of squamous or nonsquamous NSCLC, resectable clinical Stage II, IIIA or IIIB (with nodal involvement [N2]) per AJCC eighth edition guidelines (Appendix 8). No restaging is required at the time of randomization. Note: Lymph node disease requires histological confirmation if it will affect stage grouping stratification, otherwise imaging can act as a surrogate for pathological staging. Type of Participant and Disease Characteristics. Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods: Criteria 2. Confirmation that EGFR-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R]). Note: If participant’s tumor has a predominantly squamous histology, molecular testing for EGFR mutation is not required. Type of Participant and Disease Characteristics. Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods: Criteria 3. Able to undergo surgery based on opinion of investigator after consultation with surgeon. Type of Participant and Disease Characteristics. Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods: Criteria 4. Able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy. Note: Participants with resectable NSCLC (Criterion 1) previously treated outside the study with neoadjuvant pembrolizumab and platinum-based chemotherapy and successfully completed surgery with surgical tumor tissue sample available, may advance to screening for the pre-randomization period (see Section 1.3.3). Type of Participant and Disease Characteristics. Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods: Criteria 5. An ECOG performance status of 0 to 1 assessed within 10 days before first dose of study treatment. Type of Participant and Disease Characteristics. Criteria 6 through 11 apply to screening for the adjuvant period only, before randomization: Criteria 6. Achieved R0 or R1 resection status (see Section 8.1.8.3 for definitions). Type of Participant and Disease Characteristics. Criteria 6 through 11 apply to screening for the adjuvant period only, before randomization: Criteria 7. Has not achieved pCR at surgery by local review of pathology. See Section 4.1 for definition of pCR. Type of Participant and Disease Characteristics. Criteria 6 through 11 apply to screening for the adjuvant period only, before randomization: Criteria 8. Tumor tissue sample from surgical resection has been provided for determination of PD-L1 and TROP2 status by central vendor before randomization into the adjuvant period. Submission of additional tumor specimen from surgical resection may be required before randomization if initial tumor tissue submitted was not evaluable. Details pertaining to tumor tissue submission can be found in the Laboratory Manual. Type of Participant and Disease Characteristics. Criteria 6 through 11 apply to screening for the adjuvant period only, before randomization: Criteria 9. Confirmed to be disease-free based on re-baseline radiological assessment as documented by contrast enhanced chest/abdomen/pelvis CT (or MRI) within 28 days before randomization. Note: Participants may not be randomized/allocated without BICR verification of disease-free status. Type of Participant
Exclusion criteria
Exclusion criteria: Prior/Concomitant Therapy: Exclusion Criteria #6, 10, and 11 do not apply to participants entering screening during the adjuvant period after receiving neoadjuvant therapy and surgery outside the study. Criteria 11. Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention. Prior/Concomitant Therapy: Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids. Prior/Concomitant Therapy: Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Refer to Section 6.5 for information on COVID-19 vaccines. Medical conditions: Has one of the following tumor locations/types: • NSCLC involving the superior sulcus • Large cell neuro-endocrine cancer (LCNEC) • Sarcomatoid tumor • Diagnosis of SCLC or, for mixed tumors, presence of small cell elements • Documentation by local test report indicating presence of ALK gene rearrangements (ALK status not required and unknown or undetermined ALK status are acceptable, central testing will not be provided) Medical conditions: Has Grade =2 peripheral neuropathy. Medical conditions: Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing. Medical conditions: Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea). Medical conditions: Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention. Prior/Concomitant Therapy: Exclusion Criteria #6, 10, and 11 do not apply to participants entering screening during the adjuvant period after receiving neoadjuvant therapy and surgery outside the study. Criteria 6. Received prior neoadjuvant therapy for their current NSCLC diagnosis. Prior/Concomitant Therapy: Received prior treatment with a TROP2-targeted ADC. Prior/Concomitant Therapy: Received prior treatment with a topoisomerase I inhibitor-containing ADC. Prior/Concomitant Therapy: Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study. Note: A list of strong inhibitors or inducers of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers Prior/Concomitant Therapy: Exclusion Criteria #6, 10, and 11 do not apply to participants entering screening during the adjuvant period after receiving neoadjuvant therapy and surgery outside the study. Criteria 10. Received prior therapy with an 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). Prior/Concurrent Clinical Study Experience: Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administrat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of images according to RECIST 1.1 principle or biopsy; both evaluated by the BICR (Blinded Independent Central Review). NAME OF THE RESULT: Efficacy endpoint: BICR disease-free survival (DFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to any recurrence (local, locoregional, regional, or distant) as assessed by blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST 1.1), the occurrence of a new primary NSCLC or death from any cause, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of images according to RECIST 1.1 principle or biopsy; both evaluated by the BICR (Blinded Independent Central Review). NAME OF THE RESULT: Efficacy endpoint: BICR disease-free survival (DFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to any recurrence (local, locoregional, regional, or distant) as assessed by blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST 1.1), the occurrence of a new primary NSCLC or death from any cause, whichever comes first.;Follow-up regarding overall survival until death. NAME OF THE RESULT: Efficacy endpoints: Overall survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to death from any cause.;Identification of the first metastases, through imaging and biopsy/pathology. NAME OF THE RESULT: Efficacy endpoints: Distant metastasis-free survival (DMFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to first documented distant metastases, as assessed by the investigator, or death from any cause, whichever occurs first.;Evaluation of images according to RECIST 1.1 principle or biopsy; both evaluated by the BICR (Blinded Independent Central Review). NAME OF THE RESULT: Efficacy endpoints: Disease-free survival (DFS) as assessed by the investigator PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to any recurrence (local, locoregional, regional, or distant), the occurrence of a new primary NSCLC, as assessed by the investigator, or death from any cause, whichever occurs first.;Identification of death from lung cancer. NAME OF THE RESULT: Efficacy endpoints: Lung cancer-specific survival (LCSS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czech Republic, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Korea South, Mexico, Nederland, New Zealand, Norway, Peru, Poland, Portugal, Romania, Spain, Switzerland, Taiwan, Turkey, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed