Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance MK-2870 in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- Nab-paclitaxel
- Conditions
- Not specified
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 851
- Locations
- 412
- Primary Endpoint
- Overall survival (OS)
- Status
- Recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
This is a phase 3 study of pembrolizumab in combination with carboplatin/taxane (paclitaxel or nab-paclitaxel) followed by pembrolizumab with or without maintenance sacituzumab tirumotecan (sac-TMT; MK-2870) in first-line treatment of metastatic squamous non-small cell lung cancer. It is hypothesized that pembrolizumab with maintenance sacituzumab tirumotecan is superior to pembrolizumab without sacituzumab tirumotecan maintenance with respect to overall survival (OS).
Detailed Description
All participants undergo an initial induction phase of four cycles, each cycle consisting of pembrolizumab every 3 weeks (q3w) + carboplatin q3w + paclitaxel q3w or nabpaclitaxel weekly. Participants are then randomly assigned to pembrolizumab maintenance vs. pembrolizumab + sac-TMT maintenance.
Investigators
Niyati Bhagwati
Scientific
Merck Sharp & Dohme LLC
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
- •Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiology
- •Has life expectancy ≥3 months
- •Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
- •Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are hepatitis B surface antigen (HBsAg)-positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- •Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible)
- •Has adequate organ function
Exclusion Criteria
- •Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
- •History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
- •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 other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
- •HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
- •Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T lymphocyte-associated protein 4, OX-40, CD137). Note: Prior treatment with an anti-PD-1 or anti-PD-L1 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
- •Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antidrug conjugate (ADC)
- •Received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
- •Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
Arms & Interventions
Maintenance Arm B: Pembrolizumab Monotherapy
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.
Intervention: Nab-paclitaxel
Maintenance Arm A: Pembrolizumab + sac-TMT
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.
Intervention: Pembrolizumab
Maintenance Arm A: Pembrolizumab + sac-TMT
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.
Intervention: sac-TMT
Maintenance Arm B: Pembrolizumab Monotherapy
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.
Intervention: Pembrolizumab
Maintenance Arm B: Pembrolizumab Monotherapy
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.
Intervention: Carboplatin
Maintenance Arm A: Pembrolizumab + sac-TMT
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.
Intervention: Paclitaxel
Maintenance Arm B: Pembrolizumab Monotherapy
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.
Intervention: Paclitaxel
Maintenance Arm A: Pembrolizumab + sac-TMT
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.
Intervention: Carboplatin
Maintenance Arm A: Pembrolizumab + sac-TMT
During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.
Intervention: Nab-paclitaxel
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: Up to ~50 months
OS is the time from randomization to death due to any cause.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to ~79 months)
- Number of Participants With ≥1 Adverse Event (AE)(Up to ~79 months)
- Number of Participants Discontinuing from Study Therapy Due to AE(s)(Up to ~79 months)
- Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Global health status/Quality of Life (QoL) Score (EORTC QLQ-C30 Items 29 and 30)(Baseline and up to ~79 months)
- Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Dyspnea (EORTC QLQ-C30 Item 8)(Baseline and up to ~79 months)
- Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Cough (EORTC QLQ-LC13 Item 31)(Baseline and up to ~79 months)
- Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Chest Pain (EORTC QLQ-LC13 Item 40)(Baseline and up to ~79 months)
- Time to First Deterioration (TTD) in Global Health Status/QoL Scores (EORTC QLQ-C30 Items 29 and 30)(Up to ~79 months)
- TTD in Dyspnea Score (EORTC QLQ-C30 Item 8)(Up to ~79 months)
- TTD in Cough Score (EORTC QLQ-LC13 Item 31)(Up to ~79 months)
- TTD in Chest Pain Score (EORTC QLQ-LC13 Item 40)(Up to ~79 months)