Cutaneous Melanoma, Microsatellite Instability-High (MSI-H), Non-melanoma Skin Cancer (NMSC), Non-Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
RPL-001-16, Stage IIIb-IV Unresectable Melanoma, Non-melanoma Skin Cancer, Mismatch Repair Deficient (dMMR) Solid Tumors
Brief summary
The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).
Interventions
BIOLOGICALRP1
Genetically modified herpes simplex type 1 virus
BIOLOGICALnivolumab
anti-PD-1 monoclonal antibody
Sponsors
Replimune Inc.
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * At least one measurable and injectable lesion * Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy * Have a predicted life expectancy of ≥ 3 months * Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria * Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy. * Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment. * Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status * Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment. Key
Exclusion criteria
* Prior treatment with an oncolytic therapy * History of viral infections according to the protocol * Prior complications with herpes infections * Chronic use of anti-virals * Uncontrolled/untreated brain metastasis * History of interstitial lung disease * History of non-infectious pneumonitis * History of clinically significant cardiovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of adverse events (AEs) | 26 months | Percentage of subjects with adverse events (AEs) |
| Percentage of serious adverse events (SAEs) | 26 months | Percentage of subjects with serious adverse events (SAEs) |
| Percentage of dose limiting toxicities (DLTs) | 26 months | Percentage of subjects with dose limiting toxicities (DLTs) |
| Percentage of overall response rate (ORR) | 26 months | Percentage of overall response rate (ORR) for all participants |
| Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 | 20 weeks | Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of biologic activity | 20 weeks | Percentage of subjects with biological activity determined by tumor biopsies and biomarker data |
| Percentage subjects with detectable RP1 | 20 weeks | Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1 |
| Percentage of complete response (CR) | 26 months | Percentage of subjects with a complete response (CR) |
| Median duration of response | 26 months | Median duration of response of subjects |
| Median progression-free survival | 26 months | Median duration of progression-free survival of subjects |
| Median overall survival | 26 months | Median overall survival rate of subjects |
Countries
France, Germany, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJeannie Hou, MD
Replimune Inc.
Outcome results
None listed