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: 20.0Level: 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-DE
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 625
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
1. Has carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors.
2. Has disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
3. Has a life expectancy of less than 3 months and/or has rapidly progressing disease (eg tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.
4. Has a history of bleeding requiring a medical intervention (eg, embolization procedure, RBC transfusion, or hospitalization) within 30 days of study enrollment.
5. Has a history of peripheral neuropathy = Grade 2 for participants who may receive cisplatin.
6. Has a history of dihydropyrimidine dehydrogenase (DPD) deficiency (homozygous or heterozygous mutations).
7. Has a history of any contraindication or has a severe hypersensitivity to any components of epacadostat, pembrolizumab (=Grade 3), cisplatin or carboplatin, cetuximab, and 5-FU.
8. Had an allogeneic tissue/solid organ transplant.
9. Has a history of gastrointestinal condition or procedure that may affect drug absorption.
10. Any history of Serotonin Syndrome after receiving serotonergic drugs.
11. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment (see Appendix 5). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
12. Has received prior systemic therapy (as part of multimodal treatment) for HNSCC administered in the recurrent and/or metastatic setting for incurable disease.
13. Has not fully recovered (ie, =Grade 1 or at baseline) from AEs due to a previously administered treatment.
14. Has received prior palliative radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
15. Has received prior therapy with epacadostat or any IDO1 inhibitor, an anti PD-1, anti-PD-L1, or anti PD-L2 agent, or any agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
16. Has received a live vaccine within 30 days prior to the first dose of study treatment.
17. Has received therapy with an MAOI, melatonin supplement, or UGT1A9 inhibitor within 21 days prior to starting treatment, or anticipates requiring one of these prohibited medications during the treatment phase.
18. Current use of any prohibited medication as described in Section 7.7.3 of the protocol
19. Is currently participating in or has participated in a study of aninvestigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
20. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Corticosteroid use as pre-medication for allergic reactions (eg IV contrast) is permitted.
21. Has a known additional malignancy that is progressing or has required active systemic treatment within the past 3 years.
22. Has known active central nervous system metastases and/or carcinomatous meningitis.
23. Has an active autoimmune disease that has required systemic treatment
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