Clinical trial NCT02611960: Study of Pembrolizumab (MK-3475) in Platinum Pre-treated Recurrent/Metastatic Nasopharyngeal Cancer (MK-3475-122/KEYNOTE-122)
Official title: A Two-arm, Open-label, Randomized Phase III Study of Pembrolizumab (MK-3475) Monotherapy Versus Standard Chemotherapy in Platinum Pre-treated, Recurrent or Metastatic Nasopharyngeal Cancer (NPC) (Keynote-122)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasopharyngeal Neoplasms
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-11-23
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Hepatitis B or C positive
* Live vaccine within 30 days of planned start of study drug

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
Secondary outcomes:
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
measure: Objective Response Rate (ORR) Per RECIST 1.1
timeFrame: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
measure: Duration of Response (DOR) Per RECIST 1.1
timeFrame: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
measure: Percentage of Participants Surviving (OS Rate) at 12 Months
timeFrame: 12 months
measure: Percentage of Participants Surviving (OS Rate) at 24 Months
timeFrame: 24 months
measure: Percentage of Participants With PFS (PFS Rate) at 6 Months
timeFrame: 6 months
measure: Percentage of Participants With PFS (PFS Rate) at 12 Months
timeFrame: 12 months
measure: Percentage of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 73 months
measure: Percentage of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 72 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.