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Nasopharyngeal NeoplasmsPhase 3NCT02611960

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

A Phase 3 study testing Pembrolizumab, Capecitabine and Gemcitabine in people with Nasopharyngeal Neoplasms, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nasopharyngeal Neoplasms
What is being tested?
Pembrolizumab, Capecitabine and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
233 participants
Where
No sites listed yet
Study dates
18 Apr 2016to 30 Sep 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

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)

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.

Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Medical subject headings
Nasopharyngeal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02611960
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants 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).
Receives: Biological: Pembrolizumab
Standard TreatmentActive comparatorParticipants 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.
Receives: Drug: Capecitabine; Drug: Gemcitabine; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

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

    PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded independent central review (BICR), or death due to any cause, whichever occurs earlier. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. PFS 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.

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

  2. Objective Response Rate (ORR) Per RECIST 1.1

    ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. ORR 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.

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

  3. Duration of Response (DOR) Per RECIST 1.1

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. DOR 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.

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

  4. Percentage of Participants Surviving (OS Rate) at 12 Months

    OS 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. The percentage of participants surviving (OS rate) at 12 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. 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.

    Measured: 12 months

  5. Percentage of Participants Surviving (OS Rate) at 24 Months

    OS 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. The percentage of participants surviving (OS rate) at 24 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. 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.

    Measured: 24 months

  6. Percentage of Participants With PFS (PFS Rate) at 6 Months

    PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs earlier. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. The percentage of participants with PFS (PFS rate) at 6 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. 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.

    Measured: 6 months

  7. Percentage of Participants With PFS (PFS Rate) at 12 Months

    PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs earlier. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. The percentage of participants with PFS (PFS rate) at 12 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. 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.

    Measured: 12 months

  8. Percentage of Participants Who Experience One or More Adverse Events (AEs)

    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The percentage of participants that experienced at least one AE 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.

    Measured: Up to approximately 73 months

  9. Percentage of Participants Who Discontinue Study Treatment Due to an AE

    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The percentage of participants that discontinued study treatment due to an AE 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.

    Measured: Up to approximately 72 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2015 (estimated)
  2. Study start18 Apr 2016
  3. Primary completion30 Nov 2020
  4. Study completion30 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
233 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02611960
Sponsor's protocol ID
3475-122
Other IDs
MK-3475-122, KEYNOTE-122
Status last verified
Jun 2023
First submitted
19 Nov 2015
Last updated
13 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 36535566

  • 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.

    PubMed 41631899

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Capecitabine and Gemcitabine in people with Nasopharyngeal Neoplasms, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02611960, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2023.

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