Cancer of Head and Neck, Head and Neck Cancer, Neoplasms, Head and Neck, Carcinoma, Squamous Cell of Head and Neck, Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma, Head and Neck
Conditions
Brief summary
The goal of this trial is to test the ability of MK-3475 (pembrolizumab) to improve locoregional recurrence and distant metastatic rates in high-risk patients with locally advanced head and neck squamous cell carcinomas (HNSCCs) that are treated with current standard of care surgical approaches.
Interventions
BIOLOGICALMK-3475 (neoadjuvant)
PROCEDURESurgery
Standard of care
RADIATIONIntensity modulated radiation therapy
Recommended, standard of care
RADIATIONImage-guided radiation therapy
Recommended, standard of care
DRUGCisplatin
Standard of care
BIOLOGICALMK-3475 (adjuvant)
PROCEDUREPeripheral blood
-Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery
Sponsors
Merck Sharp & Dohme LLC
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed stage III or IV HNSCC oral cavity, hypopharynx, oropharynx, larynx (excluding p16 or HPV-positive oropharynx primaries and sinonasal primaries). * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam by RECIST 1.1. * At least 18 years of age. * ECOG performance status ≤ 1 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mcl * Platelets ≥ 100,000/mcl * Hemoglobin ≥ 9 g/dL * Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases) * Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 30 mL/min/1.73 m2 for patients with creatinine levels \> 1.5 x IULN * INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants * aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants * Sexually active women of childbearing potential and men must agree to use 2 methods of contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 120 days after last dose of MK-3475. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion criteria
* Prior treatment for head and neck cancer. * Patients with HPV-positive or p16-positive oropharyngeal SCCA. * Patients with sinonasal SCCAs * Patients with metastatic SCCA neck disease with an unknown primary tumor site * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). * Received a live vaccine within 30 days prior to the first dose of MK-3475. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated viruses and are not allowed. * A history of other malignancy ≤ 3 years previous with the exception of previous head and neck cancer treated only by surgery, basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix. Note: patients with synchronous head and neck cancer primaries are an exception to this criterion and may qualify for the study. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of MK-3475. * Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of MK-3475. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements. * Has an active autoimmune disease that has required systemic treatment in the 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. * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry. * Known history of active TB (bacillus tuberculosis). * Known history of hepatitis B (defined as hepatitis B survace antigen \[HBsAg\] reactive) or known active hepatitis C (defined as HCV RNA \[qualitative\] is detected) infection. Note: know testing for hepatitis B and hepatitis C is required unless mandated by local health authority. * Known history of HIV (HIV 1/2 antibodies).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional Recurrence Rates in Cohorts 1 and 2 | Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose) | -The percentage of participants who developed local-regional recurrence within one year of surgery |
| Distant Failure Rate in Cohorts 1 and 2 | Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose) | -The percentage of participants who developed distant failure within one year of surgery. Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed. |
| Rate of Major Pathologic Treatment Effect in Cohort 1 | At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose) | * Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%). |
| Rate of Major Pathologic Treatment Effect in Cohort 2 | At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose) | * Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) in Cohorts 1 and 2 | Through completion of follow-up (estimated to be 5 years after treatment) | Event-free survival will be defined as time from surgery to time to disease recurrence, distant metastasis, new primary, or death due to any cause, whichever occurred first. |
| Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Through 30 days after last dose of MK-3475 | Reportable adverse events will be tracked for 30 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events thought to be possibly, probably, or definitely related to MK-3475. Events thought to be probably or definitely related to surgery, adjuvant chemotherapy, or radiotherapy need not be recorded. |
| Overall Survival (OS) Rates Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2 | Through completion of follow-up (estimated to be 5 years after treatment)] | Overall survival will be defined as time from surgery to death from any cause. |
| Event-free Survival (EFS) Rate Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2 | Through completion of follow-up (estimated to be 5 years after treatment) | Event-free survival will be defined as time from surgery to time to disease recurrence, distant metastasis, new primary, or death due to any cause, whichever occurred first. |
| Number of Surgical Complications and/or Delays in Cohorts 1 and 2 | At the time of surgery (approximately 2-3 weeks after registration) | — |
| Locoregional Recurrence Rates in Cohorts 1 and 2 | Through completion of follow-up (estimated to be 5 years after treatment) | — |
| Rate of Distant Metastases (DM) in Cohorts 1 and 2 | Through completion of follow-up (estimated to be 5 years after treatment) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 * MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery.
* Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of:
* risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions)
* optional image-guided radiation therapy
* risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course
* MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based surgical pathology from standard of care surgery. These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. | 36 |
| Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery). | 30 |
| Not Assigned to an Arm (Cohort) -Participants who did not receive any treatment and were not assigned to an arm (cohort). | 1 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Total | Not Assigned to an Arm (Cohort) | Cohort 2: Neoadjuvant MK-3475 |
|---|---|---|---|---|
| Age, Continuous | 59.5 years | 61 years | 51 years | 62.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 64 Participants | 1 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 57 Participants | 0 Participants | 28 Participants |
| Region of Enrollment United States | 36 participants | 67 participants | 1 participants | 30 participants |
| Sex: Female, Male Female | 10 Participants | 20 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 26 Participants | 47 Participants | 1 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 36 | 2 / 30 |
| other Total, other adverse events | 36 / 36 | 30 / 30 |
| serious Total, serious adverse events | 3 / 36 | 1 / 30 |
Outcome results
Primary
Distant Failure Rate in Cohorts 1 and 2
-The percentage of participants who developed distant failure within one year of surgery. Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed.
Time frame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
Population: -Evaluable Cohort 1 participants for this outcome measure were those who had a high-risk pathology in the surgical specimen after one dose of neoadjuvant MK-3475 (pembrolizumab).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Distant Failure Rate in Cohorts 1 and 2 | 3 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Distant Failure Rate in Cohorts 1 and 2 | 1 Participants |
Primary
Locoregional Recurrence Rates in Cohorts 1 and 2
-The percentage of participants who developed local-regional recurrence within one year of surgery
Time frame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
Population: Evaluable Cohort 1 participants for this outcome measure were those who had a high-risk pathology in the surgical specimen after one dose of neoadjuvant MK-3475 (pembrolizumab).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Locoregional Recurrence Rates in Cohorts 1 and 2 | 2 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Locoregional Recurrence Rates in Cohorts 1 and 2 | 2 Participants |
Primary
Rate of Major Pathologic Treatment Effect in Cohort 1
* Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%).
Time frame: At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
Population: Only those participants enrolled in Cohort 1 were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 1 | pTR-0 | 20 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 1 | pTR-1 | 8 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 1 | pTR-2 | 8 Participants |
Primary
Rate of Major Pathologic Treatment Effect in Cohort 2
* Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%).
Time frame: At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose)
Population: Only those participants enrolled in Cohort 2 were evaluable for this outcome measure. One participant in Cohort 2 not evaluable for this outcome measure because the participant did not have surgery. One participant in Cohort 2 not evaluable because the data was missing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2: Neoadjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 2 | pTR-0 | 13 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 2 | pTR-1 | 2 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Rate of Major Pathologic Treatment Effect in Cohort 2 | pTR-2 | 13 Participants |
Secondary
Event-free Survival (EFS) in Cohorts 1 and 2
Event-free survival will be defined as time from surgery to time to disease recurrence, distant metastasis, new primary, or death due to any cause, whichever occurred first.
Time frame: Through completion of follow-up (estimated to be 5 years after treatment)
Secondary
Event-free Survival (EFS) Rate Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2
Event-free survival will be defined as time from surgery to time to disease recurrence, distant metastasis, new primary, or death due to any cause, whichever occurred first.
Time frame: Through completion of follow-up (estimated to be 5 years after treatment)
Secondary
Locoregional Recurrence Rates in Cohorts 1 and 2
Time frame: Through completion of follow-up (estimated to be 5 years after treatment)
Secondary
Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events
Reportable adverse events will be tracked for 30 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events thought to be possibly, probably, or definitely related to MK-3475. Events thought to be probably or definitely related to surgery, adjuvant chemotherapy, or radiotherapy need not be recorded.
Time frame: Through 30 days after last dose of MK-3475
Population: Only 12 participants in Cohort 1 received adjuvant MK-3475.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 diarrhea (adjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fatigue (neoadjuvant period) | 2 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fever (neoadjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 tumor flare (neoadjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 AST increase (neoadjuvant period) | 0 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 ALT increase (neoadjuvant period) | 0 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fatigue (adjuvant period) | 2 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 hypothyroidism (adjuvant period) | 3 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 3-4 hypothyroidism (adjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 AST increase (adjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 ALT increase (adjuvant period) | 1 Participants |
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 alkaline phosphatase increase (adjuvant period) | 1 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 ALT increase (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 diarrhea (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fatigue (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fatigue (neoadjuvant period) | 3 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 AST increase (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 fever (neoadjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 hypothyroidism (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 tumor flare (neoadjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 alkaline phosphatase increase (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 AST increase (neoadjuvant period) | 2 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 3-4 hypothyroidism (adjuvant period) | 0 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events | Grades 1-2 ALT increase (neoadjuvant period) | 2 Participants |
Secondary
Number of Surgical Complications and/or Delays in Cohorts 1 and 2
Time frame: At the time of surgery (approximately 2-3 weeks after registration)
Population: One participant in Cohort 2 is not evaluable for the outcome measure because the participant did not have surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 | Number of Surgical Complications and/or Delays in Cohorts 1 and 2 | 5 Participants |
| Cohort 2: Neoadjuvant MK-3475 | Number of Surgical Complications and/or Delays in Cohorts 1 and 2 | 6 Participants |
Secondary
Overall Survival (OS) Rates Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2
Overall survival will be defined as time from surgery to death from any cause.
Time frame: Through completion of follow-up (estimated to be 5 years after treatment)]
Secondary
Rate of Distant Metastases (DM) in Cohorts 1 and 2
Time frame: Through completion of follow-up (estimated to be 5 years after treatment)