CLINICAL TRIAL / NCT06422143
Pembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]
- Interventional
- Recruiting
- NCT06422143
Contact Information
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
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).
All participants undergo an initial induction phase of four cycles, each cycle consisting
of a once every 3 weeks (q3w) cycle of pembrolizumab q3w + carboplatin q3w + paclitaxel
q3w or nabpaclitaxel weekly. Participants are then randomly assigned to pembrolizumab
maintenance vs. pembrolizumab + sac-TMT maintenance.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of squamous 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
- 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
- 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
- For Maintenance only (prior to randomization): has adequate organ function
Exclusion Criteria:
- Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell
elements
- Grade ≥2 peripheral neuropathy
- History of documented severe dry eye syndrome, severe Meibomian gland disease and/or
blepharitis, or corneal disease that prevents/delays corneal healing
- Active inflammatory bowel disease requiring immunosuppressive medication or previous
history of inflammatory bowel disease
- 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 anticancer therapy for their metastatic NSCLC
- Received prior therapy with an anti-programmed cell death-1 (PD-1), anti-PD-Ligand 1
(PD-L1), or anti-PD-Lignad 2 (PD-L2) agent, or with an agent directed to another
stimulatory or coinhibitory T-cell receptor (eg, cytotoxic Tlymphocyte-associated
protein 4, OX-40, CD137) [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 treatment with a tumor-associated calcium signal transducer 2
(TROP2)-targeted antidrug conjugate (ADC)
- Received prior systemic anticancer therapy including investigational agents within 4
weeks before allocation
- 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
- Active inflammatory bowel disease requiring immunosuppressive medication or previous
history of inflammatory bowel disease
- 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
(participants with previously treated brain metastases may participate provided they
are clinically stable for t least 2 weeks and, have no evidence of new or enlarging
brain metastases and also are off steroids 3 days prior to dosing with study
medication. Subjects with known untreated, asymptomatic brain metastases [ie, no
neurological symptoms, no requirements for corticosteroids, no or minimal
surrounding edema, and no lesion >1.5 cm] may participate but will require regular
imaging of the brain as a site of disease)
- 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