Pembrolizumab With or Without Maintenance MK‑2870 in Metastatic Squamous NSCLC
- Conditions
- Participants with treatment-naïve metastatic squamous Non-small Cell Lung Cancer (NSCLC)
- Interventions
- Drug: -
- Registration Number
- 2023-510128-66-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
To compare pembrolizumab with or without maintenance MK-2870 with respect to OS
- Detailed Description
All participants undergo an initial induction phase of four cycles, each cycle consisting of pembrolizumab q3w + carboplatin q3w + paclitaxel q3w or nabpaclitaxel weekly. Participants are then randomly assigned to pembrolizumab maintenance vs. pembrolizumab + sac-TMT maintenance.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 288
- 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). Note: Participants with Grade =2 neuropathy are eligible
- Has adequate organ function
- For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12 or most recent scan before randomization
- For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
- For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
- 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
- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Participants who have not adequately recovered from major surgery or have ongoing surgical complications
- Received prior treatment with a topoisomerase I inhibitor-containing ADC
- Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Has known central nervous system (CNS) metastases/carcinomatous meningitis
- Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
- Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy [eg, thyroxine, insulin, or physiologic corticosteroid] is allowed)
- History of (noninfectious)pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Active infection requiring systemic therapy
- History of allogeneic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description - - Participants receiving -
- Primary Outcome Measures
Name Time Method Overall survival (OS) Overall survival (OS)
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Progression-Free Survival (PFS)
Number of participants with one or more adverse events (AEs) Number of participants with one or more adverse events (AEs)
Number of participants who discontinue from the study due to an AE Number of participants who discontinue from the study due to an AE
Change in score from baseline in the global health status/quality of life (QoL) score (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 items 29 and 30)) Change in score from baseline in the global health status/quality of life (QoL) score (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 items 29 and 30))
Change in score from baseline in the Dyspnea score (EORTC QLQ-C30 item 8) Change in score from baseline in the Dyspnea score (EORTC QLQ-C30 item 8)
Change in score from baseline in the Cough score (European Organisation for Research and Treatment of Cancer Lung-Specific Quality of Life Questionnaire (EORTC QLQ-LC13 item 31)) Change in score from baseline in the Cough score (European Organisation for Research and Treatment of Cancer Lung-Specific Quality of Life Questionnaire (EORTC QLQ-LC13 item 31))
Change in score from baseline in the Chest pain score (EORTC QLQ-LC13 item 40) Change in score from baseline in the Chest pain score (EORTC QLQ-LC13 item 40)
Time to Deterioration (TTD) based on change from baseline in Global health status/QoL score (EORTC QLQ-C30 items 29 and 30) Time to Deterioration (TTD) based on change from baseline in Global health status/QoL score (EORTC QLQ-C30 items 29 and 30)
TTD based on change from baseline in Dyspnea score (EORTC QLQ-C30 item 8) TTD based on change from baseline in Dyspnea score (EORTC QLQ-C30 item 8)
TTD based on change from baseline in Cough score (EORTC QLQ-LC13 item 31) TTD based on change from baseline in Cough score (EORTC QLQ-LC13 item 31)
TTD based on change from baseline in Chest pain score (EORTC QLQ-LC13 item 40) TTD based on change from baseline in Chest pain score (EORTC QLQ-LC13 item 40)
Trial Locations
- Locations (199)
CARTI Cancer Center ( Site 0006)
🇺🇸Little Rock, Arkansas, United States
Roy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Site 0122)
🇺🇸Burbank, California, United States
Exempla Lutheran Medical Center ( Site 0119)
🇺🇸Golden, Colorado, United States
Intermountain Health St. Mary's Regional Hospital ( Site 0116)
🇺🇸Grand Junction, Colorado, United States
Mid Florida Hematology and Oncology Center ( Site 0109)
🇺🇸Orange City, Florida, United States
Centricity Research Columbus Cancer Center ( Site 0111)
🇺🇸Columbus, Georgia, United States
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0001)
🇺🇸Marietta, Georgia, United States
Southeastern Regional Medical Center ( Site 0004)
🇺🇸Newnan, Georgia, United States
University of Chicago Medical Center ( Site 0145)
🇺🇸Chicago, Illinois, United States
Allina Health Cancer Institute - Abbott Northwestern Hospital ( Site 0146)
🇺🇸Minneapolis, Minnesota, United States
Scroll for more (189 remaining)CARTI Cancer Center ( Site 0006)🇺🇸Little Rock, Arkansas, United StatesStudy CoordinatorContact501-906-3000