Description:
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D), as well as to evaluate preliminary efficacy.
Title
- Brief Title: Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
- Official Title: An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
RPL-001-16
- NCT ID:
NCT03767348
Conditions
- Cancer
- Melanoma (Skin)
- Melanoma, Uveal
- Melanoma, Ocular
- Bladder Cancer
- Mismatch Repair Deficiency
- Microsatellite Instability
- Non-melanoma Skin Cancer
Interventions
Drug | Synonyms | Arms |
---|
RP1 | | Dose escalation of RP1 by IT injection |
nivolumab | Opdivo | Dose expansion of RP1 and nivolumab (IV) |
Purpose
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D), as well as to evaluate preliminary efficacy.
Detailed Description
RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly
destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open
label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to
evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of
RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors. The study will include a dose escalation phase for single agent RP1, an
expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified
tumor types for the combination therapy.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose escalation of RP1 by intratumoral (IT) injection | Experimental | Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors | |
Dose escalation of RP1 by IT injection | Experimental | Dose escalation of RP1 alone in 3 cohorts with intratumoral injections in deep/visceral tumors | |
Dose expansion of RP1 and nivolumab intravenously (IV) | Experimental | Doses of RP1 (IT) in superficial tumors with nivolumab (IV) | |
Dose expansion of RP1 and nivolumab (IV) | Experimental | Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV) | |
RP1 (IT) and nivolumab (IV) in melanoma | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma | |
RP1 (IT) and nivolumab (IV) in bladder cancer | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with bladder cancer | |
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors | |
RP1 (IT) and nivolumab (IV) in NMSC | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with NMSC | |
RP1(IT) and nivo(IV) in anti-PD1 Refractory Cutaneous Melanoma | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy for at least 12 weeks and have confirmed disease progression | |
Eligibility Criteria
Inclusion Criteria:
- Must be willing and able to participate and comply with all trial requirements and
able to provide signed and dated informed consent prior to initiation of any trial
procedures
- Male or Female ≥ 18 years of age
- Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- At least one measurable and injectable lesion
- Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance
with the study protocol
- Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test at
screening and a negative urine pregnancy test prior to administration of each dose of
RP1 or nivolumab
- WOCBP must agree to use adequate birth control throughout their participation and for
3 months after RP1 alone and 5 months after nivolumab last study treatment
- Males with partners of child-bearing potential must agree to use adequate birth
control throughout their participation and for 3 months for RP1 alone and 7 months
after nivolumab last study treatment
For Subjects in the Combination Treatment
- Baseline ECG that does not show abnormalities according to the protocol
- Baseline oxygen saturation levels that do not show abnormalities according to the
protocol
- Have provided a former tumor pathology specimen or be willing to supply a new tumor
sample from a biopsy
For Subjects in Phase 2 only
- Have a predicted life expectancy of ≥ 3 months
- Evaluable or measurable disease, according to Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 criteria,
- Subjects with melanoma: has Stage IIIb to IV (skin, eye or mucosal) for whom anti PD-1
therapy is indicated or who have previously received an anti-PD-1 therapy, or have
refused, become intolerant to or have no further therapy options available
- Subjects with MSI-H tumors: has diagnosis of MSI-H tumor (according to protocol
definition) for whom anti PD-1 therapy is indicated, or have refused, become
intolerant to or have no further therapy options available
- Subject with dMMR tumors: has diagnosis of dMMR tumor (according to protocol
definition) for whom anti PD-1 therapy is indicated, or have refused, become
intolerant to or have no further therapy options available
- Subject 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) for whom anti PD-1 therapy is indicated, or have refused,
become intolerant to or have no further therapy options available
- Subjects with bladder cancer: diagnosis of locally advanced or metastatic bladder
cancer for whom anti PD-1 therapy is indicated, or have refused, become intolerant to
or have no further therapy options available
- Subjects with cutaneous melanoma, that have confirmed progressive disease after at
least 12 weeks of anti-PD1 treatment
Exclusion Criteria:
- Prior treatment with an oncolytic therapy
- History of viral infections according to the protocol
- Systemic infection requiring IV antibiotics within 14 days prior to dosing
- Prior complications with herpes infections
- Chronic use of anti-virals
- Systemic therapies for cancer within 4 weeks of first dose (some others may be
accepted with shorter time periods)
- Conditions that require certain doses of steroids (some doses and types will be
permitted)
- Known active brain metastases - previously treated brain metastases may be permitted
- Prior certain other diagnosis of cancer
- Is participating in another clinical study or has participated in the past 4 weeks
prior to the first dose
Combination Phase Subjects
- Certain autoimmune diseases, some types will be permitted
- Allergy or sensitivity to study drug components
- History of interstitial lung disease
- History of non-infectious pnuemonitis
- Other serious or uncontrolled medical disorders
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of adverse events (AEs) |
Time Frame: | 26 months |
Safety Issue: | |
Description: | Percentage of subjects with adverse events (AEs) |
Secondary Outcome Measures
Measure: | Percentage of biologic activity |
Time Frame: | 20 weeks |
Safety Issue: | |
Description: | Percentage of subjects with biological activity determined by tumor biopsies and biomarker data |
Measure: | Percentage subjects with detectable RP1 |
Time Frame: | 20 weeks |
Safety Issue: | |
Description: | Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1 |
Measure: | Percentage of complete response (CR) |
Time Frame: | 26 months |
Safety Issue: | |
Description: | Percentage of subjects with a complete response (CR) |
Measure: | Median duration of response |
Time Frame: | 26 months |
Safety Issue: | |
Description: | Median duration of response of subjects |
Measure: | Median progression-free survival |
Time Frame: | 26 months |
Safety Issue: | |
Description: | Median duration of progression-free survival of subjects |
Measure: | Median overall survival |
Time Frame: | 26 months |
Safety Issue: | |
Description: | Median overall survival rate of subjects |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Replimune Inc. |
Last Updated
March 2, 2020