Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Mucosal Melanoma, Metastatic Non-Cutaneous Melanoma, Non-Cutaneous Melanoma, Recurrent Cutaneous Melanoma, Recurrent Mucosal Melanoma, Recurrent Non-Cutaneous Melanoma
Conditions
Brief summary
This randomized phase III trial studies how well pembrolizumab works compared with the current standard of care, physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab, in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether pembrolizumab is more effective than the current standard of care in treating patients with melanoma.
Detailed description
PRIMARY OBJECTIVES: I. To compare overall survival (OS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon recombinant interferon alfa-2b (alfa-2b) or ipilimumab versus MK-3475 (pembrolizumab). II. Among patients who are PD-L1 positive, to compare OS of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab versus MK-3475 (pembrolizumab). III. To compare relapse-free survival (RFS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab to MK-3475 (pembrolizumab). SECONDARY OBJECTIVES: I. To estimate OS and RFS for patients who are PD-L1 negative or PD-L1 indeterminate in this population. II. To compare OS and RFS of patients between the two arms within PD-L1 positive and negative subgroups and to look at the interaction between PD-L1 (positive versus negative) and treatment arm. III. To assess the safety and tolerability of the regimens. ADDITIONAL OBJECTIVES: I. To bank tissue and whole blood in anticipation of future correlative studies in this patient population. II. To evaluate PD-L1 expression through immunohistochemistry assay. III. To evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of quality of life (QOL) using the Functional Assessment of Cancer Therapy (FACT)-Biological Response Modifiers (BRM), European Quality of Life Five Dimension Three Level Scale (EQ-5D-3L), and Functional Assessment of Chronic Illness Therapy Diarrhea (FACIT-D) between patients treated with physician/patient choice of either high-dose interferon alfa-2b or ipilimumab and MK-3475 (pembrolizumab). IV. Pharmacokinetic (PK) and anti-drug antibody (ADA) testing will be performed on all patients receiving MK-3475 (pembrolizumab). TRANSLATIONAL OBJECTIVES RELATED TO T-CELL RECEPTOR BETA CHAIN SEQUENCING: I. To evaluate the association between TCR beta variable gene (TRBV) haplotype and grade 3-4 immune-related adverse events (irAEs) among stage III melanoma patients treated with adjuvant ipilimumab or pembrolizumab. II. To describe the TRBV haplotype distribution among this cohort of patients studied. TRANSLATIONAL MEDICINAL OBJECTIVE RELATED TO ASSOCIATION OF CIRCULATING TUMOR DNA (ctDNA) WITH RELAPSE-FREE SURVIVAL IN HIGH-RISK, RESECTED MELANOMA PATIENTS. I. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms. II. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms. III. To evaluate associations between pretreatment ctDNA and relapse within 2 years of randomization in a case-control analysis within each treatment arm (after treatment arm data are unblinded to investigators). IV. To evaluate associations between "early-on treatment" ctDNA levels and relapse within 2 years of randomization. V. To describe ctDNA levels at end of therapy and time of relapse. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: INDUCTION THERAPY: Patients receive high-dose recombinant interferon alfa-2B intravenously (IV) over 20 minutes on days 1-5. Treatment repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive high-dose recombinant interferon alfa-2B subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, 6 and 12 weeks, every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT scan
BIOLOGICALIpilimumab
Given IV
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
BIOLOGICALPembrolizumab
Given IV
PROCEDUREPositron Emission Tomography
Undergo PET scan
OTHERQuality-of-Life Assessment
Ancillary studies
BIOLOGICALRecombinant Interferon Alfa-2b
Given IV and SC
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* STEP 1 REGISTRATION: * Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with non-ulcerated T1b N1a disease are not eligible; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible * Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site; nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by hematoxylin and eosin (H \& E) stained slides * Patients with multiple regional nodal basin involvement are eligible; gross or microscopic extracapsular nodal extension is permitted * Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present; patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and must have no evidence of disease at the primary site or must undergo re-resection of the primary site; a full lymphadenectomy meeting the criteria outlined is required for all node-positive patients including those with positive sentinel nodes; patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected; for all patients, all disease must have been resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma; patients must be registered within 98 days of the last surgery performed to render the patient free of disease * Patients must have available and be willing to submit a minimum of five unstained slides from primary, lymph node, or metastatic site to determine PD-L1 expression; the tumor tissue must be adequate for PD-L1 testing (defined as \>= 100 tumor cells as confirmed by the treating institution's local pathologist); this must be documented by having a pathologist sign the S1404 Local Pathology Review form prior to step 1 registration; the specimens may come from an archived block but must be submitted within 20 days from cutting the slides * Patients must be offered the opportunity to participate in specimen banking as outlined * Patients must be willing to have blood draws for PK/ADA analysis as outlined, should the patient be randomized to the MK-3475 arm * Patients may have received prior radiation therapy, including after the surgical resection; all adverse events associated with prior surgery and radiation therapy must have resolved to =\< grade 1 prior to registration * Patients must not have received neoadjuvant treatment for their melanoma; patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, pegylated (PEG)-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study * Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after step 2 registration * All patients must have disease-free status documented by a complete physical examination and imaging studies within 42 days prior to registration; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan that is of diagnostic quality (with or without brain) or a CT of the chest, abdomen and pelvis; for patients with melanoma arising from the head and neck, dedicated neck imaging (CT with IV contrast or PET-CT through the region) is required; if the patient has had unknown primary with disease in the axilla, neck imaging is required to assure region is clear of cancer; CT imaging should be done with intravenous contrast if there are no contraindications for it; any other clinically-indicated imaging studies if performed (e.g. bone scan) must show no evidence of disease * All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 90 days prior to registration; the brain CT or MRI should be performed with intravenous contrast (unless contraindicated) * Absolute neutrophil count (ANC) \>= 1,500 microliter (mcL) (within 42 days prior to registration) * Platelets \>= 100,000 mcL (within 42 days prior to registration) * Hemoglobin \>= 10 g/dL (within 42 days prior to registration) * Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin \< 3.0 mg/dL) (within 42 days prior to registration) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2 x IULN (within 42 days prior to registration) * Alkaline phosphatase =\< 2 x IULN (within 42 days prior to registration) * Serum creatinine =\< IULN OR measured or calculated creatinine clearance \>= 60 mL/min (within 42 days prior to registration) * Patients must have lactate dehydrogenase (LDH) performed within 42 days prior to registration * Patients must have Zubrod performance status =\< 1 * Patients must have a baseline electrocardiogram (ECG) performed within 42 days of registration that is normal or considered not clinically significant by the site investigator * Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis * Patients must not have an active infection requiring systemic therapy * Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed * Patients known to be human immunodeficiency virus (HIV) positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate cluster of differentiation 4 (CD4) counts (\>= 350 mm\^3), and serum HIV viral load of \< 25,000 IU/ml; patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria * Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration * Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years * Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing due to unknown teratogenic side effects * Patients who are able to complete questionnaires in English, Spanish or French must participate in the quality of life assessments; (those patients who cannot complete the quality of life questionnaires in English, Spanish or French can be registered to S1404 without contributing to the quality of life studies) * Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * STEP 2 REGISTRATION (RANDOMIZATION CRITERIA): * Patients must not be registered until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 working days of receiving the e-mail notification * Women of childbearing potential must plan to have a urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required * No tests or exams are required to be repeated for step 2 registration (randomization); however, patients who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration; for example, ANC is not required to be repeated between step 1 and step 2 registration, but the most recent ANC performed before step 2 registration is required to be \>= 1,500 mcL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 5 years after last randomization | Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact. The results were presented as 5-year OS estimate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival (RFS) | 5 years after last randomization | Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact. |
| Overall Survival (OS) in Participants Who Are PD-L1 Positive | 94 months; from study start November 10, 2015 to September 15, 2023 | Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact. |
| Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive | 5 years after last randomization | Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact. |
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Randomized patients will be followed until death or 94 months (from study start November 10, 2015 to September 15, 2023), whichever occurs first. | Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for all AE reporting. |
Countries
Canada, Ireland, United States
Contacts
PRINCIPAL_INVESTIGATORSapna Patel
SWOG Cancer Research Network
Participant flow
Recruitment details
1,301 participants were randomized (SOC arm=654 and Pembrolizumab arm=647). On the SOC arm, 40 participants assigned to HD-IFN didn't receive intervention (36 due to refusal and 4 due to other reasons) and 49 participants assigned to ipilimumab did not receive intervention (41 due to refusal, 2 due to early progression, and 6 due to other reasons). 8 participants assigned to Pembrolizumab didn't receive intervention (4 due to refusal, 2 due to early progression, and 2 due to other reasons).
Participants by arm
| Arm | Count |
|---|---|
| FDA Approved Regimen (SOC) Participants receive physician/patient choice of either high-dose recombinant interferon alfa-2B (HD-IFN) or Ipilimumab as follows:
HD-IFN Induction: IV over 20 mins on days 1-5. Tx repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
Maintenance: SC on days 1, 3, and 5. Tx repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity.
Ipilimumab Induction: IV over 90 mins on day 1. Tx repeats every 3 weeks for a total of 4 cycles in the absence of disease progression or unacceptable toxicity.
Maintenance: IV over 90 mins on day 1. Tx repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity. | 654 |
| MK-3475 (Pembrolizumab) Participants receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. | 647 |
| Total | 1,301 |
Baseline characteristics
| Characteristic | FDA Approved Regimen (SOC) | Total | MK-3475 (Pembrolizumab) |
|---|---|---|---|
| Age, Continuous | 57.0 years | 56.75 years | 55.9 years |
| PD-L1 Status Indeterminate | 25 Participants | 44 Participants | 19 Participants |
| PD-L1 Status Negative | 93 Participants | 187 Participants | 94 Participants |
| PD-L1 Status Positive | 536 Participants | 1070 Participants | 534 Participants |
| Performance Status 0 | 549 Participants | 1090 Participants | 541 Participants |
| Performance Status 1 | 105 Participants | 211 Participants | 106 Participants |
| Planned Control Arm Regimen Enrolled prior to amendment | 35 Participants | 75 Participants | 40 Participants |
| Planned Control Arm Regimen High Dose Interferon | 154 Participants | 307 Participants | 153 Participants |
| Planned Control Arm Regimen Ipilimumab | 465 Participants | 919 Participants | 454 Participants |
| Race/Ethnicity, Customized Hispanic No | 617 Participants | 1221 Participants | 604 Participants |
| Race/Ethnicity, Customized Hispanic Unknown | 19 Participants | 36 Participants | 17 Participants |
| Race/Ethnicity, Customized Hispanic Yes | 18 Participants | 44 Participants | 26 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Multi-Racial | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Unknown | 17 Participants | 35 Participants | 18 Participants |
| Race/Ethnicity, Customized Race White | 621 Participants | 1243 Participants | 622 Participants |
| Sex: Female, Male Female | 259 Participants | 523 Participants | 264 Participants |
| Sex: Female, Male Male | 395 Participants | 778 Participants | 383 Participants |
| Stage IIIA | 69 Participants | 145 Participants | 76 Participants |
| Stage IIIB | 324 Participants | 635 Participants | 311 Participants |
| Stage IIIC | 222 Participants | 442 Participants | 220 Participants |
| Stage IV | 39 Participants | 79 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 130 / 654 | 131 / 647 |
| other Total, other adverse events | 557 / 565 | 622 / 639 |
| serious Total, serious adverse events | 23 / 565 | 125 / 639 |
Outcome results
Primary
Overall Survival (OS)
Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact. The results were presented as 5-year OS estimate.
Time frame: 5 years after last randomization
Population: The analysis population includes the 1301 participants who were eligible and evaluable (654 in the SOC arm and 647 in the MK-3475 arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDA Approved Regimen (SOC) | Overall Survival (OS) | 76 percentage of participants |
| MK-3475 (Pembrolizumab) | Overall Survival (OS) | 82 percentage of participants |
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for all AE reporting.
Time frame: Randomized patients will be followed until death or 94 months (from study start November 10, 2015 to September 15, 2023), whichever occurs first.
Population: Participants who were eligible and received at least one dose of protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertriglyceridemia | 8 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoalbuminemia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 4 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duodenal ulcer | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 14 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspepsia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypothyroidism | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 12 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blurred vision | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Immune system disorders - Other, specify | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalitis infection | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthritis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalopathy | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint effusion | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Endocrine disorders - Other, specify | 4 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukemia secondary to oncology chemotherapy | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 9 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis | 6 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 5 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bronchospasm | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lower gastrointestinal hemorrhage | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis infectious | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 33 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 14 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erectile dysfunction | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Meningitis | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CPK increased | 5 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Metabolism and nutrition disorders - Other, specify | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Eye disorders - Other, specify | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac disorders - Other, specify | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 5 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Eye pain | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atelectasis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocarditis | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Facial nerve disorder | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin T increased | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 9 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 4 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neuralgia | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 30 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 51 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 35 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain in extremity | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain of skin | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colonic perforation | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Papulopustular rash | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Forced expiratory volume decreased | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pharyngitis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleural effusion | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastritis | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 5 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial flutter | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proctitis | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proteinuria | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cough | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 6 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 44 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 31 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash pustular | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 12 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Autoimmune disorder | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Restrictive cardiomyopathy | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatic pain | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Retinal detachment | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cystitis noninfective | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Retinal tear | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatitis viral | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Seizure | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus tachycardia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hiccups | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinusitis | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 3 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 4 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 4 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 6 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypersomnia | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tremor | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acidosis | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vitreous hemorrhage | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 7 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 9 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 54 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 2 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperthyroidism | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wheezing | 0 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood and lymphatic system disorders - Other | 1 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 19 Participants |
| FDA Approved Regimen (SOC) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 6 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acidosis | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 4 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 19 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 3 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthritis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 14 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atelectasis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial flutter | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Autoimmune disorder | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood and lymphatic system disorders - Other | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blurred vision | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bronchospasm | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CPK increased | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac disorders - Other, specify | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin T increased | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 13 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colonic perforation | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cough | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cystitis noninfective | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 18 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duodenal ulcer | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspepsia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 4 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalitis infection | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Encephalopathy | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Endocrine disorders - Other, specify | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis infectious | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erectile dysfunction | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Eye disorders - Other, specify | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Eye pain | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Facial nerve disorder | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 3 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Forced expiratory volume decreased | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastritis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 3 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatic pain | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatitis viral | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hiccups | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 7 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypersomnia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperthyroidism | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertriglyceridemia | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoalbuminemia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 9 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypophosphatemia | 3 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypothyroidism | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Immune system disorders - Other, specify | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infusion related reaction | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint effusion | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukemia secondary to oncology chemotherapy | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lower gastrointestinal hemorrhage | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 4 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 3 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Meningitis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Metabolism and nutrition disorders - Other, specify | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocarditis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neuralgia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain in extremity | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain of skin | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 5 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Papulopustular rash | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pharyngitis | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleural effusion | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 4 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proctitis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proteinuria | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 9 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash pustular | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Restrictive cardiomyopathy | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Retinal detachment | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Retinal tear | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Seizure | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus tachycardia | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinusitis | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 2 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tremor | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vitreous hemorrhage | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| MK-3475 (Pembrolizumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wheezing | 1 Participants |
Secondary
Overall Survival (OS) in Participants Who Are PD-L1 Positive
Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact.
Time frame: 94 months; from study start November 10, 2015 to September 15, 2023
Population: The analysis population includes the 1070 participants who were eligible and evaluable with a PDL-1 positive status (536 in the SOC arm and 534 in the MK-3475 arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDA Approved Regimen (SOC) | Overall Survival (OS) in Participants Who Are PD-L1 Positive | 79 percentage of participants |
| MK-3475 (Pembrolizumab) | Overall Survival (OS) in Participants Who Are PD-L1 Positive | 83 percentage of participants |
Secondary
Relapse-free Survival (RFS)
Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact.
Time frame: 5 years after last randomization
Population: The analysis population includes the 1301 participants who were eligible and evaluable (654 in the SOC arm and 647 in the MK-3475 arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDA Approved Regimen (SOC) | Relapse-free Survival (RFS) | 49 percentage of participants |
| MK-3475 (Pembrolizumab) | Relapse-free Survival (RFS) | 58 percentage of participants |
Secondary
Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive
Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact.
Time frame: 5 years after last randomization
Population: The analysis population includes the 1070 participants who were eligible and evaluable with a PDL-1 positive status (536 in the SOC arm and 534 in the MK-3475 arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDA Approved Regimen (SOC) | Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive | 51 percentage of participants |
| MK-3475 (Pembrolizumab) | Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive | 60 percentage of participants |