Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Cisplatin

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* 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.

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery)

MK-3475 (neoadjuvant)

Surgery

Intensity modulated radiation therapy

Image-guided radiation therapy

MK-3475 (adjuvant)

-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

Peripheral blood

Douglas R Adkins, M.D.

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.

Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma

-The percentage of participants who developed local-regional recurrence within one year of surgery

-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.

* 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%).

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.

Merck Sharp & Dohme LLC

Washington University School of Medicine

The participant not assigned to an arm due to withdrawing before receiving any treatment was not followed for all-cause mortality, serious adverse events, or adverse events.

Cohort 1: Neoadjuvant MK-3475 and Adjuvant 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).

Cohort 2: Neoadjuvant MK-3475

-Participants who did not receive any treatment and were not assigned to an arm (cohort).

Not Assigned to an Arm (Cohort)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

After enrollment of 20 patients, an interim analysis was performed to assess the feasibility to achieve the primary endpoint. The trial was amended to: a) close enrollment to cohort 1 b) addition of pTR-2 after neoadjuvant pembrolizumab in all patients as a co-primary endpoint, and c) addition of cohort 2.

Douglas R. Adkins, M.D.

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery

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).

Locoregional Recurrence Rates in Cohorts 1 and 2

-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).

Distant Failure Rate in Cohorts 1 and 2

pTR-0

pTR-1

pTR-2

Only those participants enrolled in Cohort 1 were evaluable for this outcome measure.

Rate of Major Pathologic Treatment Effect in Cohort 1

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.

Rate of Major Pathologic Treatment Effect in Cohort 2

Grades 1-2 fatigue (neoadjuvant period)

Grades 1-2 fever (neoadjuvant period)

Grades 1-2 tumor flare (neoadjuvant period)

Grades 1-2 AST increase (neoadjuvant period)

Grades 1-2 ALT increase (neoadjuvant period)

Grades 1-2 fatigue (adjuvant period)

Grades 1-2 hypothyroidism (adjuvant period)

Grades 3-4 hypothyroidism (adjuvant period)

Grades 1-2 AST increase (adjuvant period)

Grades 1-2 ALT increase (adjuvant period)

Grades 1-2 alkaline phosphatase increase (adjuvant period)

Grades 1-2 diarrhea (adjuvant period)

Only 12 participants in Cohort 1 received adjuvant MK-3475.

Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events

One participant in Cohort 2 is not evaluable for the outcome measure because the participant did not have surgery.

Spots Global Cancer Trial Database for Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

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