A Phase 1b/3, Multicenter, Trial of Talimogene Laherparepvec in Combination With Pembrolizumab (MK-3475) for Treatment of Unresectable, Stage IIIB to IVM1c Melanoma (MASTERKEY-265)
- Conditions
- 1) Unresectable stage IIIB to IVM1c melanoma2) Unremoved melanoma (type of skin cancer)10040900
- Registration Number
- NL-OMON50729
- Lead Sponsor
- Amgen
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
• Male or female age >= 18 years with histologically confirmed diagnosis of
melanoma and stage IIIB to IVM1c for whom surgery is not recommended. Subjects
must have measurable disease and be a candidate for intralesional therapy
administration into cutaneous, subcutaneous, or nodal lesions. Subjects must
have ECOG performance status of 0 or 1, and adequate hematologic, hepatic,
renal, and coagulation function.
• Subjects with serine/threonine protein kinase B-Raf V600 (BRAFV600) wild-type
tumors must not have received any prior systemic anticancer treatment
consisting of chemotherapy, immunotherapy, or targeted therapy given in a
non-adjuvant setting for unresectable stage IIIB to IVM1c melanoma. Subjects
with BRAFV600 mutated tumors who have received prior BRAF inhibitor therapy
either alone or in combination with MEK inhibitor as their only prior systemic
therapy are eligible for the phase 3 of this study.
• Subjects with BRAFV600 mutant melanoma or unknown BRAFV600 mutation status
who have not received a BRAF inhibitor are also eligible for the phase 3 of
this study as first-line treatment if they meet the following criteria: lactate
dehydrogenase (LDH) < upper limit of normal (ULN), no clinically significant
tumor related symptoms, and absence of rapidly progressing metastatic
melanoma.
• Subjects (BRAF mutant, wildtype and UNK) who received prior adjuvant therapy
for melanoma will not be excluded with the exception that prior adjuvant
therapy with inhibitors of PD-1 or PD-L1 is not allowed. However, if the
subject received adjuvant therapy, the subject must have completed therapy at
least 28 days prior to enrollment.
• Subjects must have a tumor sample (archival sample or newly obtained biopsy)
that is adequate for PD-L1 assessment prior to randomization.
• Subjects must not have clinically active cerebral metastases and/or
carcinomatous meningitis. Subjects with up to 3 cerebral metastases may be
enrolled, provided that all lesions have been adequately treated with
stereotactic radiation therapy, craniotomy, or Gamma Knife therapy, with no
evidence of progression, and not requiring steroids, for at least 2 months
prior to enrollment.
Carcinomatous meningitis is excluded regardless of clinical stability
• Subjects must not have primary uveal or mucosal melanoma, history or evidence
of melanoma associated with immunodeficiency states or history of other
malignancy within the past 3 years with the exceptions of the prior
malignancies noted in Section 4.1.3.
• Subjects may not have been previously treated with T-VEC, any other oncolytic
virus, pembrolizumab, or any other inhibitor of PD-1, PD-L1, or programmed cell
death ligand 2 (PD-L2).
• Prior treatment with other immunotherapies is allowed only in the adjuvant
setting.
• Subjects must not have history or evidence of symptomatic autoimmune
glomerulonephritis, vasculitis, other symptomatic autoimmune disease,
documented history of autoimmune disease or syndrome requiring systemic
treatment in the past 2 years except vitiligo or resolved childhood
asthma/atopy, or evidence of clinically significant immunosuppression.
• Subjects must not have active herpetic skin lesions or prior complications of
herpetic infection and must not require intermittent or chronic treatment with
an antiherpetic drug, other than intermittent topical use.
For a full list of eligibility criteria please refer to Section 4.1.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS (response evaluation by blinded independent central review assessed using<br /><br>modified RECIST 1.1) (PFS1) and OS</p><br>
- Secondary Outcome Measures
Name Time Method <p>- iCRR by blinded independent central review using modified irRC-RECIST<br /><br>- iPFS by blinded independent central review using modified irRC-RECIST (PFS2)<br /><br>- OS in subjects excluding stage IVM1c per CRF<br /><br>- ORR (CR+PR), BOR, DRR, DOR, and DCR (response evaluation by blinded<br /><br>independent central review assessed using modified RECIST 1.1 and iORR (iCR +<br /><br>iPR), iBOR, iDRR, iDOR, and iDCR (response evaluation by blinded independent<br /><br>central review assessed using modified irRC-RECIST)<br /><br>Incidence of treatment-emergent and treatment-related AEs (all AEs, grade >= 3<br /><br>AEs, serious<br /><br>adverse events, fatal AEs, and AEs defined as events of interest), and abnormal<br /><br>laboratory<br /><br>tests<br /><br>-Changes in EORTC QLQ-C30 GHS/QoL subscale</p><br>