Phase 2 Study of Talimogene Laherparepvec in Combination With Pembrolizumab in Subjects With Unresectable/Metastatic Stage IIIB-IVM1d Melanoma Who Have Progressed on Prior Anti PD-1 Based Therapy
- Conditions
- Melanoma10040900cancer
- Registration Number
- NL-OMON54763
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
- Male or female age >= 18 years with histologically confirmed diagnosis of
melanoma, and with a disease stage IIIB, IIIC, IIID, IVM1a, IVM1b, IVM1c or
Stage IVM1d (with up to 3 cerebral metastases, provided that all lesions have
been adequately treated). Subject must be a candidate for intralesional therapy
into cutaneous, subcutaneous, or nodal melanoma lesion. Subjects must have ECOG
performance status of 0 or 1 and must have measurable disease, and adequate
organ function as determined by hematological, renal, hepatic and coagulation
laboratory criteria
- Subject must have recovered from all adverse events, due to prior anticancer
therapy, and, if subject received major surgery, must have recovered adequately
from toxicity and/or complications prior to enrollment. Subject must have had
prior treatment with a PD-1 inhibitor in the adjuvant or metastatic setting,
and must have received prior anti-PD-1 therapy for at least 2 to 3 consecutive
cycles within an 8 week period. The anti-PD-1 therapy must be the immediate
prior line of therapy before enrollment. Subject must have disease progression
as defined by RECIST v1.1 criteria.
Note: subjects with prior treatment and disease progression on more than 1 line
of anti-PD-1
therapy are excluded.
- Subjects will be enrolled into 1 of 4 cohorts based on prior anti-PD-1
experience:
o Cohort 1 - Locally Recurrent/Metastatic - Primary Resistance: subject
received anti-PD1 therapy in the locally recurrent/metastatic setting and
experienced a best overall response of disease progression or stable disease
prior to confirmed disease progression. The initial date of disease progression
must occur within 12 weeks of the last dose of a PD-1 inhibitor. OR
o Cohort 2 - Locally Recurrent/Metastatic - Acquired Resistance: subject
received anti-PD-1 therapy in the locally recurrent/metastatic setting and
experienced confirmed disease progression following a complete or partial
response on anti-PD-1 therapy per investigator assessment. The initial date of
disease progression must occur within 12 weeks of the last dose of a PD-1
inhibitor. OR
o Cohort 3 - Adjuvant Setting - Disease Free Interval < 6 months: subject
received anti PD-1 therapy in the adjuvant setting and experienced confirmed
disease progression following a disease free interval of < 6 months after
starting the adjuvant PD-1 inhibitor. OR
o Cohort 4 - Adjuvant Setting - Disease Free Interval >= 6 months: subject
received anti PD-1 therapy in the adjuvant setting and experienced confirmed
disease progression following a disease free interval of >= 6 months after
starting the adjuvant PD-1 inhibitor.
- For a full list of eligibility criteria please refer to Section 6.1 of the
protocol.
- Subject must not have rapid clinical progression due to melanoma, considered
by the investigator, or stage IVM1d with greater than 3 cerebral melanoma
metastases, or clinically active cerebral melanoma metastases requiring therapy
and/or carcinomatous meningitis regardless of clinical stability
- Subject 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 6.2 of the protocol.
- Subject must not have symptomatic autoimmune glomerulonephritis, vasculitis,
or other symptomatic autoimmune disease, or active autoimmune disease or
syndrome that has required systemic treatment in the past 2 years except
vitiligo or resolved childhood asthma/atopy, or evidence of clinically
significant immunosuppression.
- Subject must not have active herpetic skin lesions or prior complications of
herpetic infection, known human immunodeficiency virus (HIV) disease, known
acute or chronic hepatitis B or hepatitis C infection, a known history of
active Bacillus tuberculosis or a has a history of (non-infectious)
pneumonitis. Subject must not have undergone prior allogeneic hematopoietic
stem cell transplantation within the last 5 years.
- Subject must not have received prior therapy with talimogene laherparepvec or
any other oncolytic viruses, prior therapy with tumor vaccine (unless
administered in the adjuvant setting), prior systemic anti-cancer therapy
(including investigational agents) within 28 days prior to enrollment or prior
radiotherapy within 14 days of enrollment
- For a full list of eligibility criteria please refer to Section 6.2 of the
protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall response (complete response [CR] + partial response [PR]) (by<br /><br>investigator assessment using modified RECIST (Response Evaluation Criteria in<br /><br>Solid Tumors) v1.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Complete respons, BOR, durable respons, DOR, and disease control,<br /><br>(investigator assessment using modified RECIST v1.1 and modified irRC-RECIST<br /><br>(immune-related Response Criteria simulating Response Evaluation Criteria in<br /><br>Solid Tumors)) and overall response using modified irRC-RECIST by investigator<br /><br>assessment.<br /><br>- PFS (by investigator assessment using modified RECIST v1.1 and modified<br /><br>irRC-RECIST)<br /><br>- OS</p><br>