Resumen

The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation to normal saline placebo plus docetaxel. Participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) monoclonal antibody (mAb). MK-7684A is a coformulation product of pembrolizumab/vibostolimab. The dual primary hypotheses of the study are pembrolizumab/vibostolimab coformulation plus docetaxel and pembrolizumab/vibostolimab coformulation is superior to normal saline placebo plus docetaxel with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Descripción detallada

Participants may receive additional 17 cycles of pembrolizumab/vibostolimab (each cycle length = 21 days) for an additional 1 year of treatment as second course phase at investigator's discretion.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as primary therapy
Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies
Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment
Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease
Has measurable disease defined as at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Has a life expectancy of at least 3 months
Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization
Male participants randomized to docetaxel are eligible to participant if they agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) must agree to follow contraceptive guidance as per study protocol unless confirmed to be azoospermic during the intervention period and for at least 180 days after the last dose of docetaxel
Female participants must be not pregnant, not breastfeeding, and not be a woman of child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use contraception, or be abstinent from heterosexual intercourse during the intervention period and for ≥120 days after the last dose of study intervention. If a WOCBP is randomized to docetaxel, she agrees not to donate eggs and either uses contraception or be abstinent from heterosexual intercourse during the treatment period and for ≥180 days after the last dose of docetaxel
Has adequate organ function

Criterios de exclusión

Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
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
Has received docetaxel as monotherapy or in combination with other therapies
Has received previous treatment with another agent targeting the T-cell immunoreceptor with immunoglobulin \[Ig\] and immunoreceptor tyrosine-based inhibitory motif \[ITIM\] domains (TIGIT) pathway
Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
Has severe hypersensitivity (≥Grade 3) to docetaxel or pembrolizumab/vibostolimab coformulation and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention
Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment
Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
Has had an allogenic tissue/solid organ transplant
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Intervenciones

biological

Pembrolizumab/Vibostolimab coformulation

Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.

drug

Docetaxel

Docetaxel 75 mg\^m2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. Docetaxel will serve as part of an experimental treatment in Arm 1, and as an active comparator in Arm 3.

drug

Placebo

Normal saline IV infusion Q3W up to approximately 2 years

Ubicaciones

Centro de Oncología e Investigación de Buenos Aires ( Site 0008)

Berazategui, Buenos Aires, Argentina

Hospital Privado de Comunidad ( Site 0004)

Mar del Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0002)