Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Phase 2

Recruiting

• Conditions: Non-melanoma Skin Cancer; Microsatellite Instability; Cancer; Mismatch Repair Deficiency; Cutaneous Melanoma; NSCLC; Melanoma (Skin)
• Interventions: Biological: RP1; Biological: nivolumab

• Registration Number: NCT03767348
• Lead Sponsor: Replimune Inc.

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.

Study Timeline

• Study Start: 2017-09-20
• Study First Submitted: 2018-12-05
• Study First Submitted QC: 2018-12-05
• Study First Posted: 2018-12-06
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 340

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors	RP1	Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
RP1 (IT) and nivolumab (IV) in melanoma	RP1	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors	RP1	Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors
Dose expansion of RP1 and nivolumab (IV) in superficial tumors	nivolumab	Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma	RP1	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
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC	RP1	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC	RP1	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
RP1 (IT) and nivolumab (IV) in NMSC	RP1	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors	RP1	Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
Dose expansion of RP1 and nivolumab (IV) in superficial tumors	RP1	Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors	RP1	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 anti-PD1/PD-L1 Failed NSCLC	nivolumab	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
RP1 (IT) and nivolumab (IV) in melanoma	nivolumab	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors	nivolumab	Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma	nivolumab	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
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors	nivolumab	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	nivolumab	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC	nivolumab	Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy

Primary Outcome Measures

Name	Time	Method
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
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 overall response rate (ORR)	26 months	Percentage of overall response rate (ORR) for all participants
Percentage of dose limiting toxicities (DLTs)	26 months	Percentage of subjects with dose limiting toxicities (DLTs)

Secondary Outcome Measures

Name	Time	Method
Median duration of response	26 months	Median duration of response of subjects
Percentage of complete response (CR)	26 months	Percentage of subjects with a complete response (CR)
Median overall survival	26 months	Median overall survival rate of subjects
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
Median progression-free survival	26 months	Median duration of progression-free survival of subjects
Percentage of biologic activity	20 weeks	Percentage of subjects with biological activity determined by tumor biopsies and biomarker data

Trial Locations

Locations (52)

Hospital Clinic Barcelona; 🇪🇸 Barcelona, Spain

University of Birmingham Alabama; 🇺🇸 Birmingham, Alabama, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Carti Cancer Center; 🇺🇸 Little Rock, Arkansas, United States

UC San Diego; 🇺🇸 La Jolla, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

University of California, Irvine; 🇺🇸 Orange, California, United States

University of California- San Francisco; 🇺🇸 San Francisco, California, United States

Sylvester Comprehensive Cancer Center- University of Miami; 🇺🇸 Miami, Florida, United States

University of Iowa-Cancer Center Research; 🇺🇸 Iowa City, Iowa, United States

James Graham Brown Cancer Center- University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Atlantic Health System; 🇺🇸 Morristown, New Jersey, 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 Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

MUSC Health; 🇺🇸 Charleston, South Carolina, United States

West Cancer Center; 🇺🇸 Germantown, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Eccles Outpatient Care Center- Oncology Clinical Trials; 🇺🇸 Murray, Utah, United States

Intermountain Cancer Center- Saint George Cancer Center; 🇺🇸 Saint George, Utah, United States

Seattle Cancer Care Alliance- University of Washington; 🇺🇸 Seattle, Washington, United States

University of Wisconsin-Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States

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, France

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, Germany

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, Spain

University of Leeds- Teaching Hospital; 🇬🇧 Leeds, England, United Kingdom

Oxford University Hospitals NHS Trust; 🇬🇧 Oxford, Oxfordshire, United Kingdom

Beatson West of Scotland Cancer Center; 🇬🇧 Glasgow, Scotland, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Bebington, Wirral, United Kingdom

Royal Marsden Hospital; 🇬🇧 London, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom