Study of Pembrolizumab (MK-3475) in Platinum Pre-treated Recurrent/Metastatic Nasopharyngeal Cancer (MK-3475-122/KEYNOTE-122)

NCT02611960 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 3475-122MK-3475-122KEYNOTE-122
• Study Type: interventional
• Target: 233
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study of pembrolizumab (MK-3475) versus standard treatment (capecitabine, gemcitabine, or docetaxel) for the treatment of recurrent or metastatic nasopharyngeal cancer (NPC). Participants will be randomly assigned to receive either pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment. With Amendment 7 (effective 2-March-2022), upon study completion, participants will be discontinued and may be enrolled in an extension study.

Conditions

Nasopharyngeal Neoplasms

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall Survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last known contact. OS was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020.

  Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)

Secondary Outcomes (9)

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)

• Objective Response Rate (ORR) Per RECIST 1.1

  Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)

• Duration of Response (DOR) Per RECIST 1.1

  Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)

• Percentage of Participants Surviving (OS Rate) at 12 Months

  12 months

• Percentage of Participants Surviving (OS Rate) at 24 Months

  24 months

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) until progressive disease (PD) or unacceptable toxicity for a maximum of up to 35 cycles (up to approximately 2 years). Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab 200 mg Q3W for up to 17 cycles (up to approximately 1 additional year).

Biological: Pembrolizumab

Standard Treatment

ACTIVE COMPARATOR

Participants receive capecitabine 1000 mg/m\^2 orally (PO) twice each day (BID) on Days 1-14 of each 3-week cycle, or gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of each 3-week cycle, or docetaxel 75 mg/m\^2 IV on Day 1 of each 3-week cycle until PD or unacceptable toxicity.

Drug: Capecitabine; Drug: Gemcitabine; Drug: Docetaxel

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab

Capecitabine DRUG

oral tablet

Also known as: XELODA®

Standard Treatment

Gemcitabine DRUG

IV infusion

Also known as: GEMZAR®

Standard Treatment

Docetaxel DRUG

IV infusion

Also known as: TAXOTERE®

Standard Treatment

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed non-keratinizing differentiated NPC or undifferentiated NPC
• Metastatic disease or incurable locally recurrent disease
• Treatment with prior platinum therapy
• Tumor tissue available for programmed cell death ligand 1 (PD-L1) testing
• Measurable disease based on RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 180 days after the last dose of study drug
• Life expectancy of at least 3 months

You may not qualify if:

• Disease is suitable for local therapy administered with curative intent
• Participants previously treated in the recurrent/metastatic setting with any 1 of the 3 standard therapies in this study (i.e., docetaxel, capecitabine, or gemcitabine) may not receive the same therapy if randomized to the Standard Treatment arm. Additionally, participants previously treated in the recurrent/metastatic setting with all 3 standard therapies are excluded from this study
• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of study drug
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Not recovered from adverse events due to therapy more than 4 weeks earlier
• Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to Study Day 1, or not recovered from adverse events
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1
• Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast carcinoma
• Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents
• Active central nervous system metastases and/or carcinomatous meningitis
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Active infection requiring systemic therapy
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment for the chemotherapy arm or 120 days after the last dose of trial treatment for the pembrolizumab arm
• Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) study
• Human immunodeficiency virus (HIV) positive

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Kim SB, Ho GF, Caguioa PB, Ngamphaiboon N, Ho C, Aziz MASA, Ng QS, Yen CJ, Soparattanapaisarn N, Ngan RK, Kho SK, Tiambeng MLA, Yun T, Sriuranpong V, Algazi AP, Cheng A, Massarelli E, Swaby RF, Saraf S, Yuan J, Siu LL. Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial. Ann Oncol. 2023 Mar;34(3):251-261. doi: 10.1016/j.annonc.2022.12.007. Epub 2022 Dec 16.

  PMID: 36535566 RESULT

• Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Spreafico A, Kim SB, Ho GF, Caguioa PB, Ngamphaiboon N, Swaby RF, Wei B, Webber AL, Kang J, Gumuscu B, Yuan J, Siu LL. Analysis of Plasma Epstein-Barr Virus DNA and Clinical Outcomes to Pembrolizumab or Chemotherapy in Recurrent/Metastatic Nasopharyngeal Cancer in KEYNOTE-122. Cancer Med. 2026 Feb;15(2):e71496. doi: 10.1002/cam4.71496.

  PMID: 41631899 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Nasopharyngeal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Capecitabine; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 23, 2015
• Study Start: April 18, 2016
• Primary Completion: November 30, 2020
• Study Completion: September 30, 2022
• Last Updated: July 13, 2023
• Results First Posted: December 15, 2021

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share