Metastatic Non Small Cell Lung Cancer
Conditions
Keywords
Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD-1, PDL1, PD-L1, PD-L2
Brief summary
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).
Detailed description
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.
Interventions
BIOLOGICALPembrolizumab/Vibostolimab coformulation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.
DRUGDocetaxel
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.
DRUGPlacebo
Normal saline IV infusion Q3W up to approximately 2 years
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Arm 1 and Arm 3: Double-blind with in-house blinding Arm 2: Unblinded Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment | Up to approximately 21 months | PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment | Up to approximately 21 months | ORR is defined as the percentage of participants who have a confirmed complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 is presented. |
| Overall Survival (OS) | Up to approximately 21 months | OS is defined as the time from randomization to the date of death due to any cause. |
| Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment | Up to approximately 21 months | For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR is presented. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 39 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is reported here. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 27 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE is reported here. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Denmark, Finland, France, Germany, Israel, Italy, Malaysia, Poland, Russia, South Korea, Spain, Switzerland, Taiwan, Thailand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel Participants received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m\^2 via IV infusion Q3W. Each cycle was 21 days. | 87 |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation Participants received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W for up to 35 cycles up to approximately 2 years. Each cycle was 21 days. | 83 |
| Arm 3: Placebo + Docetaxel Participants received normal saline placebo via IV infusion Q3W for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m\^2 via IV infusion Q3W. Each cycle was 21 days. | 85 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 72 | 69 | 76 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Sponsor Decision | 12 | 12 | 7 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Arm 2: Pembrolizumab/Vibostolimab Coformulation | Arm 3: Placebo + Docetaxel | Total |
|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 8.8 | 66.0 Years STANDARD_DEVIATION 7.4 | 65.8 Years STANDARD_DEVIATION 8 | 65.5 Years STANDARD_DEVIATION 8.1 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 0 | 34 Participants | 30 Participants | 32 Participants | 96 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 1 | 53 Participants | 53 Participants | 53 Participants | 159 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 9 Participants | 6 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 68 Participants | 65 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 6 Participants | 14 Participants | 33 Participants |
| Predominant Tumor Histology Non-squamous | 61 Participants | 63 Participants | 51 Participants | 175 Participants |
| Predominant Tumor Histology Squamous | 26 Participants | 20 Participants | 34 Participants | 80 Participants |
| Prior Lines of Therapy 1 | 58 Participants | 49 Participants | 52 Participants | 159 Participants |
| Prior Lines of Therapy 2 | 25 Participants | 28 Participants | 26 Participants | 79 Participants |
| Prior Lines of Therapy 3 | 1 Participants | 4 Participants | 7 Participants | 12 Participants |
| Prior Lines of Therapy 4 | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Prior Lines of Therapy ≥5 | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS <1% | 37 Participants | 45 Participants | 34 Participants | 116 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS 1-49% | 34 Participants | 19 Participants | 35 Participants | 88 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline Tumor proportion score (TPS) ≥50% | 15 Participants | 14 Participants | 13 Participants | 42 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline Unknown (Not evaluable due to <100 viable tumor cells) | 1 Participants | 5 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 14 Participants | 10 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 5 Participants | 14 Participants | 32 Participants |
| Race (NIH/OMB) White | 62 Participants | 63 Participants | 60 Participants | 185 Participants |
| Sequence of Prior Anti-Programmed Cell Death Receptor 1 (PD-1)/PD-L1 Immediate Prior Therapy | 72 Participants | 70 Participants | 72 Participants | 214 Participants |
| Sequence of Prior Anti-Programmed Cell Death Receptor 1 (PD-1)/PD-L1 Not the Immediate Prior Therapy | 15 Participants | 13 Participants | 13 Participants | 41 Participants |
| Sex: Female, Male Female | 27 Participants | 23 Participants | 24 Participants | 74 Participants |
| Sex: Female, Male Male | 60 Participants | 60 Participants | 61 Participants | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 74 / 87 | 70 / 83 | 77 / 85 |
| other Total, other adverse events | 83 / 85 | 67 / 83 | 76 / 83 |
| serious Total, serious adverse events | 48 / 85 | 26 / 83 | 37 / 83 |
Outcome results
Primary
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment
PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR is presented.
Time frame: Up to approximately 21 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment | 5.6 Months |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment | 2.7 Months |
| Arm 3: Placebo + Docetaxel | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment | 3.2 Months |
p-value: 0.09195% CI: [0.53, 1.13]Regression, Cox
p-value: 0.962295% CI: [0.96, 2.02]Regression, Cox
Secondary
Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR is presented.
Time frame: Up to approximately 21 months
Population: All randomized participants who demonstrated a confirmed CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment | 6.5 Months |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment | NA Months |
| Arm 3: Placebo + Docetaxel | Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment | NA Months |
Secondary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE is reported here.
Time frame: Up to approximately 27 months
Population: Per protocol, the safety analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Number of Participants Who Discontinued Study Treatment Due to an AE | 42 Participants |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Number of Participants Who Discontinued Study Treatment Due to an AE | 12 Participants |
| Arm 3: Placebo + Docetaxel | Number of Participants Who Discontinued Study Treatment Due to an AE | 24 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is reported here.
Time frame: Up to approximately 39 months
Population: Per protocol, the safety analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Number of Participants Who Experienced an Adverse Event (AE) | 85 Participants |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Number of Participants Who Experienced an Adverse Event (AE) | 76 Participants |
| Arm 3: Placebo + Docetaxel | Number of Participants Who Experienced an Adverse Event (AE) | 82 Participants |
Secondary
Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment
ORR is defined as the percentage of participants who have a confirmed complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time frame: Up to approximately 21 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment | 29.9 Percentage of participants |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment | 6.0 Percentage of participants |
| Arm 3: Placebo + Docetaxel | Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment | 15.3 Percentage of participants |
p-value: 0.011395% CI: [2.1, 26.9]Miettinen & Nurminen method
p-value: 0.97595% CI: [-19.6, 0]Miettinen & Nurminen method
Secondary
Overall Survival (OS)
OS is defined as the time from randomization to the date of death due to any cause.
Time frame: Up to approximately 21 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Pembrolizumab/Vibostolimab Coformulation + Docetaxel | Overall Survival (OS) | 10.2 Months |
| Arm 2: Pembrolizumab/Vibostolimab Coformulation | Overall Survival (OS) | 7.5 Months |
| Arm 3: Placebo + Docetaxel | Overall Survival (OS) | 8.8 Months |
p-value: 0.094395% CI: [0.5, 1.15]Regression, Cox
p-value: 0.597495% CI: [0.7, 1.58]Regression, Cox