Primary Objectives:To evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by progression free survival (PFS) (response evaluation by blinded independent central review using modified…
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PFS (response evaluation by blinded independent central review assessed using
modified RECIST 1.1) (PFS1) and OS
Secondary outcome
- iCRR by blinded independent central review using modified irRC-RECIST
- iPFS by blinded independent central review using modified irRC-RECIST (PFS2)
- OS in subjects excluding stage IVM1c per CRF
- ORR (CR+PR), BOR, DRR, DOR, and DCR (response evaluation by blinded
independent central review assessed using modified RECIST 1.1 and iORR (iCR +
iPR), iBOR, iDRR, iDOR, and iDCR (response evaluation by blinded independent
central review assessed using modified irRC-RECIST)
Incidence of treatment-emergent and treatment-related AEs (all AEs, grade >= 3
AEs, serious
adverse events, fatal AEs, and AEs defined as events of interest), and abnormal
laboratory
tests
-Changes in EORTC QLQ-C30 GHS/QoL subscale
Background summary
It's expected that talimogene laherparepvec and PD-1 blockade likely play
complementary roles in regulating adaptive immunity. Talimogene laherparepvec
likely augments dendritic cell-mediated tumor antigen presentation through
local expression of GM-CSF and local antigen release by direct tumor lysis.
Pembrolizumab prevents T-cell exhaustion in peripheral tissues. The combination
of an agent that increases tumor-specific immune activation with one that
blocks inhibitory T-cell checkpoints could produce greater antitumor activity
than either agent alone. It's expected that talimogene laherparepvec in
combination with pembrolizumab will be safe and well tolerated and that
talimogene laherparepvec in combination with pembrolizumab compared to
pembrolizumab alone will improve PFS and will improve OS.
Study objective
Primary Objectives:
To evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus
placebo with pembrolizumab, as assessed by progression free survival (PFS)
(response evaluation by blinded independent central review using modified
Response Evaluation Criteria in Solid Tumors 1.1 [RECIST]) and overall survival
(OS).
Secondary Objectives:
To evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus
placebo with pembrolizumab, as assessed by:
- Complete response rate (iCRR) by blinded independent central assessed
modified immune-related response criteria simulating response evaluation
criteria in solid tumors (modified irRC-RECIST)
-iPFS by blinded independent central assessed modified irRC-RECIST
-OS in subjects excluding stage IVM1c per case report form (CRF) ORR, BOR, DRR,
DOR, DCR (response evaluation by blinded independent central review assessed
modified RECIST 1.1 and irRC-RECIST)
-To evaluate the safety of talimogene laherparepvec with pembrolizumab versus
placebo with pembrolizumab, as assessed by incidence of treatment-emergent and
treatment-related AEs and abnormal laboratory tests.
-To evaluate patient reported outcomes (PRO) in phase 3 as assessed by the
European Organization for Research and Treatment of Cancer (EORTC) Quality of
Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life
(GHS/QoL) subscale.
Study design
This is a multicenter, double-blind, placebo-controlled, randomized trial to
evaluate the efficacy, as assessed by PFS and OS of talimogene laherparepvec
with pembrolizumab versus placebo with pembrolizumab in subjects with
unresectable, stage IIIB to IVM1c melanoma. Approximately 660 subjects will be
randomized 1:1 to receive the following:
• Arm 1: talimogene laherparepvec plus pembrolizumab
• Arm 2: placebo plus pembrolizumab
Randomization will be stratified by stage of disease: less advanced stages
(IIIB, IIIC, and IVM1a) versus more advanced stages (IVM1b and IVM1c) and by
prior BRAF inhibitor therapy: no prior BRAF inhibitor versus BRAF inhibitor
with or without MEK inhibitor.
Subjects will be treated with talimogene laherparepvec in combination with
pembrolizumab (arm 1) or placebo in combination with pembrolizumab (arm 2)
until 24 months from the date of the first dose of pembrolizumab or end of
treatment for other reasons as described in Section 3.1.1.1, whichever occurs
first.
Intervention
Amgen Investigational Product Dosage and Administration:
Talimogene laherparepvec or placebo will be administered by intralesional
injection into injectable cutaneous, subcutaneous, and nodal lesions with or
without image ultrasound guidance. Investigational product must not be
administered into visceral organ metastases. See Section 6.2.1. for additional
information regarding dosage and administration information.
The initial dose of double-blind treatment is up to 4.0 mL of 106 PFU/mL
talimogene laherparepvec or placebo (talimogene laherparepvec formulation
excipients as described in the Talimogene Laherparepvec Investigator*s
Brochure). The second dose up to 4.0 mL of 108 PFU/mL talimogene laherparepvec
or placebo should be administered 21 (+3) days after the initial dose.
Subsequent doses up to 4.0 mL of 108 PFU/mL talimogene laherparepvec or placebo
should be given every 2 weeks (± 3) days until week 9 and every 3 weeks (± 3)
days thereafter. When double-blind treatment and pembrolizumab are
administered on the same day, double-blind treatment must be administered first.
Non-Amgen Investigational Product Dosage and Administration:
Pembrolizumab at a dose of 200 mg will be administered intravenously every 3
weeks (±3 days). the second dose of pembrolizumab will be administered 21 (+3)
days after the initial dose.
See Section 6.2.2 or additional information regarding dosage and administration
of pembrolizumab.
Study burden and risks
RISKS:
Adverse events related to talimogene laherparepvec en pembrolizumab. The
patient will be checked for adverse events during the hospital visits.
BURDEN:
Maximal study duration is 2 years + 60 month FU survival.
Minervum 7061
Breda 4817ZK
NL
Minervum 7061
Breda 4817ZK
NL
Listed location countries
Age
Inclusion criteria
• 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.
Exclusion criteria
• 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000185-22-NL |
| ClinicalTrials.gov | NCT02263508 |
| CCMO | NL54270.000.16 |