Pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen as first line treatment for R/M HNSCC (KEYNOTE-669/ECHO-304)
- Conditions
- Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaMedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001338-24-IT
- Lead Sponsor
- INCYTE CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 89
1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapies will be enrolled in this study.
2. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days after the last dose of pembrolizumab and epacadostat, or pembrolizumab alone, and for at least 180 days after the last dose of the EXTREME regimen, whichever is longer. He must also refrain from donating sperm during this period. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
3. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 120 days after the last dose of pembrolizumab and epacadostat, or pembrolizumab alone, and for at least 180 days after last dose of the EXTREME regimen, whichever is longer. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
5. Have measurable disease by CT or MRI based on RECIST 1.1 as determined by site radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions following radiation therapy.
6. Have an ECOG PS of 0 or 1 within 7 days prior to randomization.
7. Have adequate organ function as defined in the protocol. Specimens must be collected within =10 days prior to the start of study treatment.
8. Have documentation of results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point. If HPV status was previously tested using this method, no additional testing is required.
9. Have a baseline archival tumor specimen available or is willing to undergo a pre-study treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen. Fine needle aspirate (FNA) and bone metastases samples are not acceptable.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 437
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 188
1Hs carcin of nasopharynx,salivary gland,unknown primary origin,or nonsquamous histologies as primary tumors2Hs disease progresswithin6months of completion of curatively intended syst treat for locoregionally advancHNSCC3Hs life expectancy of less than3months and hs rapidly progressing disease(tumor bleeding,unctrltumor pain)in opinion of treating investigator 4Hs hist ofbleeding requiring a medical intervent(embolizat procedure,RBCtransfusion,or hospitalizat)within30dys ofstud enrollment5Hs a hist of peripheral neuropathy=Grade2for pt who may receive cisplatin6Hs hist ofdihydropyrimidine dehydrogenase(DPD)defic(homozygous orheterozygous mutat)7Hs hist of any contraindication or hs a severe hypersensitivity to any components of epacadostat,pembro(=Grade3),cisplatin or carboplatin,cetux,5FU8Had allogenic tissue/solidorgantransplant9Hs a hist of gastrointestinal condition or procedure that may affect drug absorption10Any hist of Serotonin Syndr after receiving serotonergic drugs11WOCBP who hs positive urine pregnancy test within72hours before first dose of stud treat(App5)If urine test cannt be confirmed negative,serum pregnancy test is required.in such cases,participant must be excluded from participation if serum pregnancy result is positive12Hs received prior syst therapy(as part of multimodal treat)forHNSCCadministered in recurrent and/or metastatic setting for incurable disease13Hs nt fully recovered(=Grade1or a baseline)fromAEs due to a previously administer treat14Hs received prior palliative radioth within2wks of start of stud treat.Pt must have recover from all radiation-related toxicities,nt require corticosteroids,nt have had radiation pneumonitis15Hs receiv prior therapy with epacadostat or anyIDO1inhib,antiPD1,antiPDL1,antiPDL2agent,or any agent directed to anther stimulatory or coinhibTcellR(CTLA4,OX40,CD137)16Hs received live vaccine within30dys prior to the first dose ofstud treat17Hs received therapy with anMAOI,melatonin supplement,UGT1A9inhibitor within21dys prior to starting treat,or anticipates requiring one of thse prohibited medicats during treat phse18Current use of any prohibited medicat as described inSect7.7.3of protocol19Is currently pt in orhs participated in a stud of aninvestigational agent or hs used an investigational device within4wks prior to first dose of stud treat20Hs a diagnosis of immunodefic or is receiving chronic syst steroid therapy(dosing exceeding10mg daily of prednisone orequivalent)or any other form of immunosuppressive therapy within7dys prior to first dose of stud treat.Corticosteroid use as premedicat for allergic react(IVcontrast)is permitted21Hs a known additional malignancy that’s progressing or hs required active syst treat within past3years22Hs known active central nervous syst metastases or carcintous meningitis23Hs active autoimm disease that hs required syst treat in past2years24Hs hist of(noninfectious)pneumonitis that required steroids orhs current pneumonitis25Hs active infection requiring syst therapy26Hs known hist of human immunodefic virus(HIV)infection.NoHIVtesting is required unless mandated by local health authority27Hs known hist of or ispositive for active hepatitisB(defined as hepatitisBsurface antig[HBsAg]reactive)or hepatitisC(defined asHCVRNAis detected)28Hs known psychiatric or substance abuse disorders that would interfere with cooperating with requirements of stud29Hs hist orcurrent evidence ofanycondition,therapy or lab abnormality that might confound the resu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method