IGNYTE: Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Sponsor

Replimune Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03767348

Collaborator

(none)

300

Enrollment

Locations

Arms

85.4

Anticipated Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Melanoma (Skin) Mismatch Repair Deficiency Microsatellite Instability Non-melanoma Skin Cancer Cutaneous Melanoma NSCLC	Biological: RP1 Biological: nivolumab	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 20, 2017

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors	Biological: RP1 Genetically modified herpes simplex type 1 virus
Experimental: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors	Biological: RP1 Genetically modified herpes simplex type 1 virus
Experimental: Dose expansion of RP1 and nivolumab (IV) in superficial tumors Doses of RP1 (IT) in superficial tumors with nivolumab (IV)	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in melanoma Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in NMSC Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma 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	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC 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	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC 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	Biological: RP1 Genetically modified herpes simplex type 1 virus Biological: nivolumab anti-PD-1 monoclonal antibody Other Names: Opdivo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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) for whom anti PD-1 therapy is indicated, or have refused, become intolerant to or have no further therapy options available
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) for whom anti-PD1/PD-L1 therapy is indicated, or have refused, become intolerant to or have no further therapy options available
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: has confirmed progressive disease after no more than two prior systemic treatments including anti-PD1/PD-L1 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Birmingham Alabama	Birmingham	Alabama	United States	35294
2	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
3	Mayo Clinic	Phoenix	Arizona	United States	85054
4	Carti Cancer Center	Little Rock	Arkansas	United States	72205
5	UC San Diego	La Jolla	California	United States	92093
6	University of Southern Californi	Los Angeles	California	United States	90033
7	UCLA	Los Angeles	California	United States	90095
8	University of California, Irvine	Orange	California	United States	92868
9	University of California- San Francisco	San Francisco	California	United States	94115
10	Sylvester Comprehensive Cancer Center- University of Miami	Miami	Florida	United States	33136
11	University of Iowa-Cancer Center Research	Iowa City	Iowa	United States	52242
12	James Graham Brown Cancer Center- University of Louisville	Louisville	Kentucky	United States	40202
13	Mayo Clinic	Rochester	Minnesota	United States	55905
14	Atlantic Health System	Morristown	New Jersey	United States	07960
15	New York University Clinical Cancer Center	New York	New York	United States	10016
16	Weill Cornell Medical College	New York	New York	United States	10065
17	University of Rochester Medical Center	Rochester	New York	United States	14642
18	Duke Cancer Center	Durham	North Carolina	United States	27710
19	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
20	Providence Portland Medical Center	Portland	Oregon	United States	97213
21	MUSC Health	Charleston	South Carolina	United States	29425
22	West Cancer Center	Germantown	Tennessee	United States	38138
23	Eccles Outpatient Care Center- Oncology Clinical Trials	Murray	Utah	United States	84107
24	Intermountain Cancer Center- Saint George Cancer Center	Saint George	Utah	United States	84790
25	Seattle Cancer Care Alliance- University of Washington	Seattle	Washington	United States	98109
26	University of Wisconsin-Carbone Cancer Center	Madison	Wisconsin	United States	53792
27	Institut Bergonié	Bordeaux		France	33076
28	CHU Dijon	Dijon		France	21079
29	CHU de Nice Hôpital l'Archet	Nice		France	06200
30	Hôpital Saint Louis APHP	Paris		France	75010
31	Institut Gustave Roussy	Villejuif		France	94800
32	Charité (Campus Benjamin Franklin)	Berlin		Germany	12203
33	University Hospital Essen, Klinik für Dermatologie	Essen		Germany	45147
34	University of Kiel (UKSH), Dep. of Dermatology	Kiel		Germany	24105
35	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
36	Hospital Clinic Barcelona	Barcelona		Spain	08036
37	Institut Catala D'Oncologia - Hospital Duran I	Barcelona		Spain	08908
38	Clínica Universidad de Navarra (Madrid)	Madrid		Spain	28027
39	Hospital Universitario Virgen de la Arrixaca	Murcia		Spain	30120
40	Clinica Universitaria de Navarra	Pamplona		Spain	31008
41	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
42	Hospital General Universitario de Valencia	Valencia		Spain	46014
43	University of Leeds- Teaching Hospital	Leeds	England	United Kingdom	LS97TF
44	Oxford University Hospitals NHS Trust	Oxford	Oxfordshire	United Kingdom
45	Beatson West of Scotland Cancer Center	Glasgow	Scotland	United Kingdom	G12 0YN
46	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral	United Kingdom	CH634JY
47	Royal Marsden Hospital	London		United Kingdom
48	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD