Health Condition 1: C761- Malignant neoplasm of thorax
Conditions
Interventions
Intervention1: Vibostolimab with
Pembrolizumab: Administered as an intravenous
(IV) infusion every 3 weeks
(Q3W)
Control Intervention1: Pembrolizumab: Administered as an intravenous
(IV) infusion ever
Sponsors
Merck Sharp Dohme LLC a subsidiary of Merck and Co Inc
Eligibility
Inclusion criteria
Inclusion criteria: 1. Has a histologically or cytologically confirmed diagnosis of NSCLC (Stage IV: M1a, M1b, M1c, AJCC Staging Manual, version 8). Note: Mixed tumors will be characterized by the predominant cell type; if small cell elements are present, the participant is ineligible. 2. Has measurable disease based on RECIST 1.1, as determined by the local site assessment. Note: Measurable disease is defined as having at least 1 measurable lesion by CT or MRI per RECIST 1.1. Lesions that appear measurable but are situated in a previously irradiated area can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation. 3. Has confirmation that EGFR-, ALK-, or ROS1 directed therapy is not indicated as primary therapy (documentation of the absence of tumor activating EGFR mutations [eg, DEL19 or L858R], AND absence of ALK and ROS1 gene rearrangements). Note: If participant’s tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines. 4. Has provided tumor tissue that demonstrates PD-L1 expression in =1% of tumor cells (TPS =1%) as assessed by IHC at a central laboratory. Note: Assessment of PD-L1 expression must be made from provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Details pertaining to tumor tissue submission can be found in the procedures manual. Demographics 5. Is male or female, = 18 years of age at the time of providing documented informed consent. 6. Has an ECOG PS of 0 or 1 assessed within 7 days prior to randomization. 7. Has a life expectancy of at least 3 months. 8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) Is not a WOCBP OR b) Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of - A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. - Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5. - The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early und
Exclusion criteria
Exclusion criteria: 1. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy 2. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. 3. Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137) Has received previous treatment with another agent targeting the T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) receptor pathway 4. Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease 5. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines is allowed. 6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention 7. Has known active or untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention 8. Has severe hypersensitivity (=Grade 3) to pembrolizumab/vibostolimab or pembrolizumab and/or any of its excipients 9. 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). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 10. 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 to the first dose of study intervention 11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 12. Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary. 13. Has an active infection requiring systemic therapy. 14. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority. 15. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =50% 2. OS in Participants With PD-L1 TPS =1% 3. OS in Participants With PD-L1 TPS 1% to 49% 4. Progression-Free Survival (PFS) in Participants With PD-L1 TPS =1% 5. PFS in Participants With PD-L1 TPS =50%Timepoint: 1. Up to 59 months 2. Up to 59 months 3. Up to 59 months 4. Up to 51 months 5. Up to 51 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 in Participants With PD-L1 TPS 1% to 49%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 in Participants With PD-L1 TPS =1%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 in Participants With PD-L1 TPS =50%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Cough Score (Item 31) on the EORTC QLQ-LC13 in Participants With PD-L1 TPS 1% to 49%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Cough Score (Item 31) on the EORTC QLQ-LC13 in Participants With PD-L1 TPS =1%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) in Participants With PD-L1 TPS =50%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 in Participants With PD-L1 TPS 1% to 49%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 in Participants With PD-L1 TPS =1%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 in Participants With PD-L1 TPS =50%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Global Health Status/QoL (Items 29, 30) Combined Score on the EORTC QLQ-C30 in Participants With PD-L1 TPS 1% to 49%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Global Health Status/QoL (Items 29, 30) Combined Score on the EORTC QLQ-C30 in Participants With PD-L1 TPS =1%Timepoint: Baseline and up to 107 weeks;Change from Baseline in Global Health Status/Quality of Life (QoL) (Items 29, 30) Combined Score on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) in Parti | — |
Countries
Brazil, Canada, Chile, China, Dominican Republic, Guatemala, Hong Kong, Hungary, India, Japan, Malaysia, Mexico, Peru, Philippines, Republic of Korea, Romania, Russian Federation, South Africa, Taiwan, Thailand, Turkey, Ukraine, United States of America, Viet Nam
Contacts
Public ContactDr Monisha Sharma
MSD Pharmaceuticals Pvt Ltd
Outcome results
None listed