Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Cancer Clinical Trial

— IGNYTE  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03767348
• Other study ID #: RPL-001-16
• Status: Recruiting
• Phase: Phase 2
• Start date: September 20, 2017
• Est. completion date: November 2024

Study information

• Verified date: August 2023
• Source: Replimune Inc.
• Contact: Clinical Trials at Replimune
• Phone: 1-781-222-9570
• Email: Clinicaltrials[@]replimune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Cutaneous Melanoma
• Melanoma
• Melanoma (Skin)
• Microsatellite Instability
• Mismatch Repair Deficiency
• Non-melanoma Skin Cancer
• NSCLC
• Skin Neoplasms

Intervention

Biological:
• RP1
Genetically modified herpes simplex type 1 virus
• nivolumab
anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
France	CHU Besancon - Hopital Jean Minjoz	Besançon
France	Institut Bergonié	Bordeaux
France	CHU Dijon	Dijon
France	Centre Léon Bérard Lyon	Lyon
France	Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone	Marseille
France	CHU de Nice Hôpital l'Archet	Nice
France	Hôpital Saint Louis APHP	Paris
France	Institut Gustave Roussy	Villejuif
Germany	Charité (Campus Benjamin Franklin)	Berlin
Germany	University Hospital Essen, Klinik für Dermatologie	Essen
Germany	University of Kiel (UKSH), Dep. of Dermatology	Kiel
Germany	Uniklinik Marburg	Marburg
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala D'Oncologia - Hospital Duran I	Barcelona
Spain	Clínica Universidad de Navarra (Madrid)	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral
United Kingdom	Beatson West of Scotland Cancer Center	Glasgow	Scotland
United Kingdom	University of Leeds- Teaching Hospital	Leeds	England
United Kingdom	Royal Marsden Hospital	London
United Kingdom	Oxford University Hospitals NHS Trust	Oxford	Oxfordshire
United Kingdom	Southampton General Hospital	Southampton
United States	University of Birmingham Alabama	Birmingham	Alabama
United States	MUSC Health	Charleston	South Carolina
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Duke Cancer Center	Durham	North Carolina
United States	West Cancer Center	Germantown	Tennessee
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa-Cancer Center Research	Iowa City	Iowa
United States	UC San Diego	La Jolla	California
United States	Carti Cancer Center	Little Rock	Arkansas
United States	UCLA	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	James Graham Brown Cancer Center- University of Louisville	Louisville	Kentucky
United States	University of Wisconsin-Carbone Cancer Center	Madison	Wisconsin
United States	Sylvester Comprehensive Cancer Center- University of Miami	Miami	Florida
United States	Atlantic Health System	Morristown	New Jersey
United States	Eccles Outpatient Care Center- Oncology Clinical Trials	Murray	Utah
United States	New York University Clinical Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	University of California, Irvine	Orange	California
United States	Mayo Clinic	Phoenix	Arizona
United States	Providence Portland Medical Center	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Intermountain Cancer Center- Saint George Cancer Center	Saint George	Utah
United States	University of California- San Francisco	San Francisco	California
United States	Seattle Cancer Care Alliance- University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Replimune Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of adverse events (AEs)	Percentage of subjects with adverse events (AEs)	26 months
Primary	Percentage of serious adverse events (SAEs)	Percentage of subjects with serious adverse events (SAEs)	26 months
Primary	Percentage of dose limiting toxicities (DLTs)	Percentage of subjects with dose limiting toxicities (DLTs)	26 months
Primary	Percentage of overall response rate (ORR)	Percentage of overall response rate (ORR) for all participants	26 months
Primary	Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1	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	20 weeks
Secondary	Percentage of biologic activity	Percentage of subjects with biological activity determined by tumor biopsies and biomarker data	20 weeks
Secondary	Percentage subjects with detectable RP1	Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1	20 weeks
Secondary	Percentage of complete response (CR)	Percentage of subjects with a complete response (CR)	26 months
Secondary	Median duration of response	Median duration of response of subjects	26 months
Secondary	Median progression-free survival	Median duration of progression-free survival of subjects	26 months
Secondary	Median overall survival	Median overall survival rate of subjects	26 months