Clinical trial NCT03767348: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cancer
Melanoma (Skin)
Mismatch Repair Deficiency
Microsatellite Instability
Non-melanoma Skin Cancer
Cutaneous Melanoma
NSCLC
Keywords: Oncolytic virus
Oncolytic Immuno-gene therapy
Non-melanoma Skin Cancer
Cutaneous Melanoma
Anti-PD1 failed
Melanoma (skin)
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-12-06
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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.

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

Primary outcomes:
measure: Percentage of adverse events (AEs)
timeFrame: 26 months
measure: Percentage of serious adverse events (SAEs)
timeFrame: 26 months
measure: Percentage of dose limiting toxicities (DLTs)
timeFrame: 26 months
measure: Percentage of overall response rate (ORR)
timeFrame: 26 months
measure: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1
timeFrame: 20 weeks
Secondary outcomes:
measure: Percentage of biologic activity
timeFrame: 20 weeks
measure: Percentage subjects with detectable RP1
timeFrame: 20 weeks
measure: Percentage of complete response (CR)
timeFrame: 26 months
measure: Median duration of response
timeFrame: 26 months
measure: Median progression-free survival
timeFrame: 26 months
measure: Median overall survival
timeFrame: 26 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Birmingham Alabama
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Little Rock
country: United States
facility: Carti Cancer Center
state: Arkansas
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: San Francisco
country: United States
facility: University of California- San Francisco
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center- University of Miami
state: Florida
city: Iowa City
country: United States
facility: University of Iowa-Cancer Center Research
state: Iowa
city: Louisville
country: United States
facility: James Graham Brown Cancer Center- University of Louisville
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: New York
country: United States
facility: New York University Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Charleston
country: United States
facility: MUSC Health
state: South Carolina
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Murray
country: United States
facility: Eccles Outpatient Care Center- Oncology Clinical Trials
state: Utah
city: Saint George
country: United States
facility: Intermountain Cancer Center- Saint George Cancer Center
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance- University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Carbone Cancer Center
state: Wisconsin
city: Besançon
country: France
facility: CHU Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié
city: Dijon
country: France
facility: CHU Dijon
city: Lyon
country: France
facility: Centre Léon Bérard Lyon
city: Marseille
country: France
facility: Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone
city: Nice
country: France
facility: CHU de Nice Hôpital l'Archet
city: Paris
country: France
facility: Hôpital Saint Louis APHP
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité (Campus Benjamin Franklin)
city: Essen
country: Germany
facility: University Hospital Essen, Klinik für Dermatologie
city: Kiel
country: Germany
facility: University of Kiel (UKSH), Dep. of Dermatology
city: Marburg
country: Germany
facility: Uniklinik Marburg
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Institut Catala D'Oncologia - Hospital Duran I
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra (Madrid)
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Leeds
country: United Kingdom
facility: University of Leeds- Teaching Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
state: Oxfordshire
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Center
state: Scotland
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
state: Wirral
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Replimune Inc.
name: Jeannie Hou, MD
role: STUDY_DIRECTOR
References:
citation: Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019 Aug 10;7(1):214. doi: 10.1186/s40425-019-0682-1.