Melanoma MedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histologically or cytologically confirmed melanoma. 2. Have unresectable Stage III or Stage IV melanoma, as per AJCC staging system not amenable to local therapy. 3. Have been untreated for advanced or metastatic disease except as follows. a. BRAF V600 mutant melanoma may have received standard of care targeted therapy (e.g. BRAF/MEK inhibitor, alone or in combination) and be eligible for this study Note: Targeted therapy is not required for eligibility. b. Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 4 weeks before randomization and all related adverse events have either returned to baseline or stabilized (resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). c. Prior adjuvant therapy containing immunotherapy such as interferon or anti-CTLA-4 therapy will only be permitted if relapse did not occur during treatment or within 6 months of treatment discontinuation. d. Prior anti-PD-1, anti-PD-L1, or IDO1 inhibitors are excluded. 4. Have documentation of V600-activating BRAF mutation status or consent to BRAF V600 mutation testing during the screening period. 5. Have laboratory parameters within Protocol-defined range. The screening laboratory tests below must be = 7 days before treatment initiation. 6. Have the presence of at least one measurable lesion by CT or MRI per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions. a. If subjects have only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from the non-target lesion or archival tissue. b. If subjects have only 1 measurable lesion per RECIST 1.1, this lesion should not have been in the field of prior irradiation unless there is documented progression of the lesion(s). 7. Provide a baseline tumor biopsy a. Subjects must submit the tumor sample during screening for PD-L1 expression testing at a central pathology laboratory. Subjects will be eligible to participate regardless of the level of PD-L1 expression, but will be stratified by PD-L1 expression level. Subjects who do not submit a sample adequate for PD-L1 determination will not be randomized. The biopsy may not be obtained from a lone target lesion. b. Newly-obtained tissue is preferred (no intervening treatment [local or systemic] involving the site of tissue biopsy once tissue biopsy is obtained at time of study enrollment). The only exception to this is a sample that was collected prior to BRAF +/- MEK targeted treatment, where the subject progressed on this targeted treatment, in cases where 1) fresh tissue or 2) archival tissue with no intervening local or systemic therapy is not possible to provide. 8. Have resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention. 9. Be male or female subjects, age 18 years or older on day of signing consent. 10. Provide written informed consent/assent for the study. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Bi
Exclusion criteria
Exclusion criteria: 1. Has received prior systemic treatment for unresectable or metastatic melanoma (except BRAF directed therapy as noted in inclusion criteria #3). 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or IDO1 inhibitor or any other antibody or drug specifically targeting checkpoint pathways other than anti-CTLA-4 which is permitted in the adjuvant setting. 3. Has received prior adjuvant therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study drug or not recovered (= Grade 1 or at baseline) from AEs due to previously administered agents. Exception to this rule would be use of denosumab, which is not excluded. Note: Subjects with = Grade 2 neuropathy are an exception and may enroll. 4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment. 5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy. 6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases confirmed by repeat imaging, and have not required steroids for at least 14 days before study treatment. 7. Has ocular melanoma. 8. Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody. For a list of excipients, refer to the respective Investigator Brochure (Section 3.3). 9. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 10. Has an active infection requiring systemic therapy. 11. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). 12. Has known history of or is positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected). 13. Has history evidence of (non-infectious) pneumonitis that required steroids or current pneumonitis. 14. Has received prior radiotherapy within 2 weeks of therapy. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (= 2 weeks of RT) to non-CNS disease. 15. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of the combination of pembrolizumab and epacadostat versus pembrolizumab and placebo (i.e. 2 treatment groups) based on RECIST 1.1 by independent central review; and To compare overall survival (OS) of the 2 treatment groups.;Secondary Objective: To compare the objective response rate (ORR) of the 2 treatment groups based on RECIST 1.1 by independent central review; To evaluate the safety and tolerability of the 2 treatment groups; To evaluate the duration of response (DOR) of the 2 treatment groups based on RECIST 1.1 by independent central review; and To evaluate the pharmacokinetics (PK) and anti-pembrolizumab antibodies of pembrolizumab and epacadostat administered concomitantly.;Primary end point(s): The dual primary endpoints are PFS and OS. • Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first. • Overall survival, defined as the time from date of randomization to date of death due to any cause. The study is considered to have met its study objective if the combination is superior to pembrolizumab and placebo in either PFS or OS. ;Timepoint(s) of evaluation of this end point: Two interim analyses (IA1, IA2) will be performed in this study: • IA1 to be performed when ~331 PFS events have been observed • IA 2 to be performed when ~420 PFS events have been observed • Final Analysis to be performed when ~293 OS events have occurred | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response rate, defined as the proportion of subjects who have best response as complete response (CR) or partial response (PR). Responses are based on independent central review using RECIST 1.1. • Duration of response (DOR) determined by disease assessment defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. Response will be determined by independent central review using RECIST 1.1. ;Timepoint(s) of evaluation of this end point: Two interim analyses (IA1, IA2) will be performed in this study: • IA1 to be performed when ~331 PFS events have been observed • IA 2 to be performed when ~420 PFS events have been observed • Final Analysis to be performed when ~293 OS events have occurred | — |
Countries
Australia, Belgium, Canada, Chile, Denmark, France, Germany, Ireland, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Russian Federation, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Outcome results
None listed