Melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: 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
Concentration u
Sponsors
MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Has histologically or cytologically confirmed melanoma. 2.Has unresectable Stage III or Stage IV melanoma, per AJCC 8th Edition Staging Criteria, not amenable to local therapy. 3.Has the presence of at least 1 measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR. a.Cutaneous lesions and other superficial lesions are not considered measurable lesions but may be considered as nontarget lesions. b.If participants have only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from the nontarget lesion or archival tissue. If biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained post-biopsy and measurable disease confirmed by BICR. c.Lesions that are in an area that has been previously irradiated should not be considered measurable unless there has been documented growth of the lesions since the completion of radiation. 4.Has been untreated for advanced disease except as follows: a.BRAF V600 mutation-positive melanoma may have received SOC targeted therapy as 1L therapy for advanced disease (eg, BRAF/MEK inhibitor, alone or in combination). b.Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-PD-1 therapy, anti-CTLA-4 or Interferon) is permitted. Prior anti-PD-1 therapy will only be permitted if relapse did not occur during treatment or within 6 months of treatment discontinuation. No other prior adjuvant or neoadjuvant therapy will be allowed. 5.Has documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during Screening (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible). 6.Has provided a tumor biopsy. a.Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized/allocated. b.Tumor sample should be freshly obtained (strongly preferred). In cases where newly obtained tissue is not possible to provide; an archival sample may be acceptable. c.If a fresh tissue sample is submitted, it is preferred that the tumor biopsy is not obtained from a lone target lesion. If the biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained post-biopsy and measurable disease confirmed by BICR. 7.Is male or female from 18 years to 120 years at the time of signing the informed consent. 8.Has an ECOG performance status 0 to 1 (as assessed within 7 days of the first dose of study intervention). 9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days, corresponding to time needed to eliminate study intervention(s) after the last dose of study intervention: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) For the remaining criteria refer to the protocol 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.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 intervention. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, topical steroids, or local steroid injections would not be excluded from the study. 2.Has a known additional malignancy that is progressing or requires active treatment within the past 2 years. Exceptions to the secondary malignancy exclusion include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, new nonulcerated primary melanoma <1 mm in depth with no nodal involvement, Grade 1 follicular lymphoma or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy. 3.Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided they are stable (without evidence of progression by imaging prior to the first dose of study intervention as evidenced by 2 scans at least 4 weeks apart providing stability, 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 intervention. The second scan showing stability may be used as baseline scan if acquired within the Screening Phase. Baseline MRI brain scan will be obtained for all participants. Brain CT scan should only be used when MRI is contraindicated. The second brain MRI showing stability may be used as baseline scan if acquired within the Screening Phase. 4.Has ocular or mucosal melanoma. 5.Has known hypersensitivity to active substances or any of their excipients. 6.Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 7.Has an active infection requiring systemic therapy. 8.Has known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies). No testing of HIV is required unless mandated by local health authority. 9.Has known history of hepatitis B (defined as HBsAg reactive) or known hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 10.Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis. 11.Has a history of active tuberculosis (TB; Bacillus tuberculosis). 12.A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 13.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, TIGIT). 14.Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization. 15.Has received prior radiotherapy within 2 weeks of the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To assess the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events (AEs) 2.To evaluate objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1);Secondary Objective: 1.To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1;Primary end point(s): 1. Percentage of participants who experience an adverse event (AE) 2. Percentage of participants who discontinue study treatment due to an AE 3. Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1);Timepoint(s) of evaluation of this end point: 1. Up to ~28 months 2. Up to ~24 months 3. Up to ~30 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Duration of response (DOR) per RECIST 1.1;Timepoint(s) of evaluation of this end point: 1. Up to ~30 months | — |
Countries
Australia, France, Germany, Greece, Hungary, Israel, Italy, New Zealand, Poland, Spain, Switzerland, United States
Contacts
Public ContactDivisione Ricerca Clinica
MSD Italia Srl
Outcome results
None listed