Pembrolizumab in Combination With CRT for LA-SCCHN

NCT02586207 | Completed Phase 1 Results DMC

• 1 other identifier: SH MISP203
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single-arm, multi-site, open-label trial of pembrolizumab (MK-3475) used in combination with standard, cisplatin-based, definitive chemoradiotherapy (CRT) in patients with stage III-IVB squamous cell carcinoma of the head and neck (SCCHN). Approximately 39 patients with Stage III-IVB SCCHN will be enrolled to evaluate both the safety and efficacy of this novel combination. Subjects will not be randomized and will all receive the study treatment. Treatment will consist of a loading dose of pembrolizumab 200 mg IV given 7 days prior to initiation of CRT (day-7). CRT with cisplatin 40 mg/m2 IV weekly and head and neck radiation at 70 Gy fractionated at 2 Gy once daily over 35 days, will begin on day 1. CRT will end on approximately day 46-50. Pembrolizumab 200 mg IV will continue following CRT in an adjuvant fashion starting on day 57 for an additional 5 doses, as tolerated, through day 141. Subjects will be evaluated for response following treatment.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma; Oral Cavity Cancer; Oropharynx Cancer; Hypopharynx Cancer; Larynx Cancer; Laryngeal Cancer

Keywords

Larynx; Squamous Cell; Oral cavity; Oropharynx; Hypopharynx

Outcome Measures

Primary Outcomes (1)

• Adverse Events Will be Assessed and Graded Using CTCAE 4.0. Occurrences With Max Grade and Percentage/Number of Participants Affected by AEs Will be Provided.

  To determine the safety and tolerability of pembrolizumab given in combination with cisplatin-based chemoradiotherapy (CRT) in subjects with treatment naive Stage III-IVB squamous cell carcinoma of the head and neck (SCCHN). Number of participants affected by AEs will be reported by grade and percentage of participants affected. Safety and tolerability will be assessed by clinical review of all relevant parameters including adverse events (AEs), laboratory tests, and vital signs. Count and percentage of AE will be provided.

  through day 240 (this time frame allows capturing of AEs that occurred up to 90 days after completion of treatment)

Secondary Outcomes (1)

• Evaluation of the Efficacy of Pembrolizumab Given in Combination With Definitive CRT by Determining the Number of Participants With Complete Response at Treatment End (Day 150)

  Day 150 (post treatment imaging)

Study Arms (1)

Single Arm

EXPERIMENTAL

Pembrolizumab + Cisplatin + Radiation

Drug: pembrolizumab (MK-3475); Drug: Cisplatin; Radiation: Radiation

Interventions

pembrolizumab (MK-3475) DRUG

200mg IV on days -7(loading dose), 15, 36, 57, 78, 99, 120, 141.

Also known as: Keytruda

Single Arm

Cisplatin DRUG

Cisplatin 40 mg/m2 IV on days 1, 8, 15, 22, 29, 36

Also known as: Platinol, Platinol-AQ

Single Arm

Radiation RADIATION

70 Gy fractionated over 35 days

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically or cytologically-confirmed head and neck squamous cell carcinoma of the oral cavity (excluding lip), oropharynx, hypopharynx, or larynx.
• Have TNM clinical stage III, IVA, or IVB disease
• Be eligible for curative-intent concurrent chemoradiation therapy
• Be willing and able to provide written informed consent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a recently obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day -7. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from Sanford Research.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined:
• Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL
• Female subject of childbearing potential should have a negative urine or serum pregnancy 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 serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Patients may not be receiving any other investigational agents, chemotherapy, immunotherapy, radiotherapy, or molecular targeted agents within 4 weeks of the start of the study treatment.
• Prior treatment with radiation to the head and neck
• Patients with TNM Stage IVC disease
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Sanford Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

UCSD Moores Cancer Center

La Jolla, California, 92093-0698, United States

Location

Sanford-Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

Location

Sanford-Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Sanford Health Cancer Center

Sioux Falls, South Dakota, 57104, United States

Location

Related Publications (7)

• Spanos WC, Nowicki P, Lee DW, Hoover A, Hostager B, Gupta A, Anderson ME, Lee JH. Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009 Nov;135(11):1137-46. doi: 10.1001/archoto.2009.159.

  PMID: 19917928 BACKGROUND

• Vermeer DW, Spanos WC, Vermeer PD, Bruns AM, Lee KM, Lee JH. Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer. Int J Cancer. 2013 Jul;133(1):120-9. doi: 10.1002/ijc.28015. Epub 2013 Feb 12.

  PMID: 23292955 BACKGROUND

• Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, Bruno TC, Richmon JD, Wang H, Bishop JA, Chen L, Drake CG, Topalian SL, Pardoll DM, Pai SI. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 2013 Mar 15;73(6):1733-41. doi: 10.1158/0008-5472.CAN-12-2384. Epub 2013 Jan 3.

  PMID: 23288508 BACKGROUND

• Seiwert T, Burtness B, Weiss J, Gluck I, Eder JP, Pai SI, et al. A phase IB study of MK-3475 in patients with human papilloma virus (HPV) associated and non-HPV associated head and neck (H/N) cancer. ASCO 2014 Abstract #6011, Jun 2014.

  BACKGROUND

• Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, Jones H, Wilkinson RW, Honeychurch J, Illidge TM. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014 Oct 1;74(19):5458-68. doi: 10.1158/0008-5472.CAN-14-1258.

  PMID: 25274032 BACKGROUND

• Parikh F, Duluc D, Imai N, Clark A, Misiukiewicz K, Bonomi M, Gupta V, Patsias A, Parides M, Demicco EG, Zhang DY, Kim-Schulze S, Kao J, Gnjatic S, Oh S, Posner MR, Sikora AG. Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer. Cancer Res. 2014 Dec 15;74(24):7205-16. doi: 10.1158/0008-5472.CAN-14-1913. Epub 2014 Oct 15.

  PMID: 25320012 BACKGROUND

• Powell SF, Gold KA, Gitau MM, Sumey CJ, Lohr MM, McGraw SC, Nowak RK, Jensen AW, Blanchard MJ, Fischer CD, Bykowski J, Ellison CA, Black LJ, Thompson PA, Callejas-Valera JL, Lee JH, Cohen EEW, Spanos WC. Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. J Clin Oncol. 2020 Jul 20;38(21):2427-2437. doi: 10.1200/JCO.19.03156. Epub 2020 Jun 1.

  PMID: 32479189 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell; Mouth Neoplasms; Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Laryngeal Diseases

Interventions

pembrolizumab; Cisplatin; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Physical Phenomena

Results Point of Contact

• Title: Steven F. Powell, MD
• Organization: Sanford Health

Steven.Powell@sanfordhealth.org

605-328-8000

Study Officials

• Steven F Powell, MD

  Sanford Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 26, 2015
• Study Start: November 1, 2015
• Primary Completion: September 29, 2020
• Study Completion: August 1, 2025
• Last Updated: October 7, 2025
• Results First Posted: January 15, 2021

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (4)