Replimune : RP1 IGNYTE Injected and Non-injected Lesions Response Analysis Poster at ASCO 2025 (1c2bcf)

Published: 2025-06-01 20:50:43 ET REPL

Published on 06/01/2025 at 20:50

Gino K. In1, Michael K. Wong2, Joseph J. Sacco3, Eva Muñoz Couselo4, Dirk Schadendorf5, Georgia M. Beasley6, Jiaxin Niu7, Bartosz Chmielowski8, Trisha M. Wise-Draper9, Mohammed M. Milhem10, Tawnya Lynn Bowles11, Katy K. Tsai12, Céleste Lebbé13, Caroline Gaudy-Marqueste14, Adel Samson15, Junhong Zhu16, Marcus Viana16, Jeannie W. Hou16, Caroline Robert17

Immune checkpoint inhibitors have improved outcomes for patients with advanced melanoma, but the majority of patients experience disease progression on anti-programmed cell death protein 1 (PD-1) therapy1-6

Outcomes following progression are poor, with a median overall survival (OS) of approximately 1 year in real-world clinical practice7,8

There is no generally established standard of care following progression, and available treatment options are limited by suboptimal efficacy and/or high toxicity9-13

RP1 (vusolimogene oderparepvec) is a selectively replication-competent herpes simplex virus type 1-based oncolytic immunotherapy that expresses human granulocyte-macrophage colony-stimulating factor and the fusogenic GALV-GP-R- glycoprotein14

In the registrational cohort from the IGNYTE trial, patients with advanced anti-PD-1-failed melanoma were treated with RP1 + nivolumab:

The objective response rate (ORR) was 32.9% by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

The complete response rate was 15.0%

Landmark OS rates at 1, 2, and 3 years were 75.3%, 63.3%, and

54.8%, respectively; median OS was not reached

Background

Safety in superficial a

Patients with deep/visceral comparable rates of treatm

Table 3. Safety by injec

nd/or deep/visceral inj

(± superficial) injections and ent-related adverse events (T

tion type (most comm

Superficial only (n = 104)

ections

patients with only superficial i

able 3)

on TRAEs related to

Deep/visceral

(n =

Deep/visceral plus superficial

(n = 14)

njections experienced

RP1 or nivolumab)

± superficial 36)

Deep/visceral only (n = 22)

TRAEs, n (%)

All grades

Grades 3/4

All grades

Grades 3/4

All grades

Grades 3/4

Total

93 (89.4)

15 (14.4)

12 (85.7)

2 (14.3)

21 (95.5)

1 (4.5)

Fatigue

33 (31.7)

1 (1.0)

6 (42.9)

7 (31.8)

Pyrexia

31 (29.8)

3 (21.4)

9 (40.9)

Chills

30 (28.8)

5 (35.7)

10 (45.5)

Nausea

22 (21.2)

3 (21.4)

6 (27.3)

Diarrhea

14 (13.5)

1 (1.0)

2 (14.3)

4 (18.2)

Vomiting

14 (13.5)

1 (7.1)

4 (18.2)

Headache

13 (12.5)

1 (7.1)

4 (18.2)

Influenza-like illness

13 (12.5)

2 (14.3)

10 (45.5)

Injection-site pain

13 (12.5)

3 (21.4)

5 (22.7)

1University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; 2Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; 3The Clatterbridge Cancer Centre, Wirral, UK and University of Liverpool, Liverpool, UK; 4Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron Hospital Medical Oncology Department, Barcelona, Spain; 5Department of Dermatology, West German Cancer Center, University Hospital Essen, Essen & National Center for Tumor Diseases (NCT-West), Campus Essen & University Alliance Ruhr, Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Campus Essen, Essen, Germany; 6Duke Cancer Institute, Duke University, Durham, NC, USA; 7Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 8Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; 9University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati, OH, USA; 10Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA; 11Intermountain Medical Center, Murray, UT, USA; 12Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; 13Université Paris Cité, AP-HP Dermato-Oncology and CIC, Cancer Institute APHP. Nord-Université Paris Cité, INSERM U976, Saint Louis Hospital, Paris, France; 14Aix-Marseille Université, APHM, Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM, U1068, CNRS, UMR7258, UM105, Hôpital Timone, CEPCM, Dermatology and Skin Cancer Department, Marseille, France; 15Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK; 16Replimune, Inc., Woburn, MA, USA; 17Gustave Roussy and Paris-Saclay University, Villejuif, France

Table 1. Efficacy by injection type by BICR using RECIST

1.1 (patient-level data)

Confirmed BOR,

n (%)

Total (N = 140)

Superficial only

(n = 104)

Deep/visceral ± superficial (n = 36)

Deep/ visceral plus superficial (n = 14)

Deep/ visceral only (n = 22)

21 (15.0)

18 (17.3)

3 (13.6)

25 (17.9)

13 (12.5)

6 (42.9)

6 (27.3)

31 (22.1)

19 (18.3)

4 (28.6)

8 (36.4)

54 (38.6)

46 (44.2)

3 (21.4)

5 (22.7)

ORR

46 (32.9)

31 (29.8)

6 (42.9)

9 (40.9)

Objective

Evaluate the efficacy of RP1 + nivolumab in injected and non-injected lesions

Assess the safety and efficacy in patients receiving superficial and/or deep/visceral RP1 injections

RP1*

Cycle 1

RP1** + Nivo†

Cycles 2-8

Nivo†

Cycle 9

Nivo‡

Cycles 10-30b

Weeks

100-day safety follow-up

Anti-PD-1-failed cutaneous melanomaa (N = 140 patients)

Weeks

Methods

aLDH level was unknown in 1 (0.7%) patient. bPD-L1 status was undetermined or missing in 17 (12.1%) patients. cPrimary resistance: Progressed within 6 months of starting the immediate prior course of anti-PD-1 therapy.

Eight (7.7%) patients in the superficial only group and 1 (7.1%) patient in the deep/visceral plus superficial group were not evaluable (discontinued prior to the first efficacy assessment).

Patients

A "real-world" anti-PD-1-failed melanoma population was enrolled (N = 140; data cutoff, March 8, 2024)

Median (range) age was 62 (21-91) years

The median (range) follow-up at the time of the primary analysis was 15.5 (0.5-47.6) months

Due to the requirement that patients must have confirmed progressive disease on an immediate prior anti-PD-1-based therapy, most patients had 1 or 2 prior lines of therapy

Patient clinical characteristics are summarized below

Sixty-eight (48.6%) patients had stage IVM1b-d disease

Lactate dehydrogenase (LDH) levels were above the upper limit of normal in 47 (33.6%) patientsa

Seventy-nine (56.4%) patients had PD-L1-negative tumorsb

Sixty-one (43.6%) patients had prior anti-PD-1 combined with anti-CTLA-4 and 4 (2.9%) received both therapies sequentially

Most patients (92 [65.7%]) had primary resistance to anti-PD-1 therapyc

RP1 lung and liver injections

RP1 injections to lung and liver lesions were feasible and resulted in responses (Figures 4 and 5)

Among 7 patients with lung injections, pneumothorax events were reported in 5.8% (3/52) of injections

One event was grade 1 and two events were grade 2; these events self-resolved, and further RP1 injections were given without additional events

For both grade 2 events, resolution occurred within 4 days

One (1.9%) lung injection led to pneumothorax requiring invasive intervention (chest tube insertion)

All events occurred within 7 days after RP1 injection

Results

permission from ASCO® or the author of this poster.

contact [email protected] or +1 (781) 222 9570.

Additional information can be obtained by visiting ClinicalTrials.gov (NCT03767348).

Overall, these data support the safety and efficacy of deep/visceral injections and demonstrate the development of a robust systemic anti-tumor response following RP1 treatment

The confirmatory phase 3 IGNYTE-3 trial (NCT06264180) is currently underway (see poster TPS9599)

Wolchok JD, et al. J Clin Oncol. 2021;40:127-37.

Larkin J, et al. N Engl J Med. 2015;373:23-34.

Lim SY, et al. Nat Commun. 2023;14:1516.

Liver and lung injections had a tolerable safety profile

No bleeding events were reported after liver injection

Lung injections were associated with low rates of pneumothorax events, which were typically of low grade and manageable

The safety and efficacy profiles of deep/visceral injections were generally comparable to those of superficial injections

Numerically higher rates of response were observed after deep/visceral injections vs superficial injections only

Deep/visceral injections can be safely and reproducibly performed

Both lesion-level and patient-level responses were seen independent of the injection status of individual lesions or their anatomical site

The overall response to RP1 was driven by the response of both injected and non-injected lesions

Conclusions

RP1 injections directly into the lung and liver were generally well tolerated and resulted in few organ-specific adverse events that were easily managed.

Patients experienced numerically higher ORRs after receiving deep/visceral injections (± superficial) compared with superficial injections only.

Deep responses were observed in injected and non-injected, including visceral, lesions.

Injected

48 liver injections in 8 patients

No elevated liver function tests

No liver or abdominal cavity bleeding events

One patient was not included because lesions were not measurable by BICR.

aPatient had a CR as a radical resection of all 3 lesions on the skin of the left foot confirmed full regression. bThe sum of diameters of 4 target lesions met the criteria for a PR. cPatient only had non-injected lesions measured.

BICR, blinded independent central review; CR, complete response; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

RP1 administration

RP1 was injected into superficial and/or deep/visceral tumors

Superficial tumors: defined as those that could be visualized or palpated and accessed with standard-sized needles and syringes

Deep/visceral tumors: defined as those that could not be directly observed or palpated and required imaging guidance (eg, ultrasound, computed tomography, endoscopy, bronchoscopy) to inject

Visceral tumors are deep tumors associated with visceral organs

Both superficial and deep/visceral lesions could be injected on the same day (volume dependent on lesion size; ≤10 mL total/day)

Recommended needle gauges are 25-27 for superficial lesions and 20-23 for deep/visceral lesions

27 months

4 months

Baseline

The primary analysis was conducted when all patients had ≥12 months of follow-up.

aConfirmed progression while being treated with ≥8 weeks of anti-PD-1 therapy, alone or in combination; anti-PD-1 must be the last prior therapy. Patients on prior adjuvant therapy must have confirmed progression while being treated with adjuvant treatment (PD can be confirmed by biopsy). bRP1 can be reinitiated beyond 8 cycles if protocol-specified criteria are met. cFor mRECIST, PD must be confirmed by further progression ≥4 weeks after initial PD; this is intended to better allow for pseudoprogression than RECIST 1.1.

BICR, blinded independent central review; CR, complete response; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; mRECIST, modified RECIST; nivo, nivolumab; ORR, objective response rate; OS, overall survival; PD, progressive disease; PD-1, programmed cell death protein 1; PFS, progression-free survival; PFU, plaque-forming units; Q2W, every 2 weeks; Q4W, every 4 weeks; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

CR, complete response; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

Study design

Efficacy in superficial and/or deep/visceral lesions

Patients with deep/visceral (± superficial) injections had numerically higher response rates vs those who received superficial injections only (Table 1)

The ORR was 40.0% (6/15) in patients receiving deep/visceral (± superficial) lung and liver injections

The median number of RP1 injections in the lung and liver was 8 and 6.5, respectively

Responses in injected vs non-injected lesions

In an analysis of injected vs non-injected lesions, up to 10 lesions per patient were analyzed by BICR

Among RECIST 1.1 responders (N = 46), robust responses were observed in both injected and non-injected lesions (Table 2 and Figure 1)

There was a ≥30% reduction in 93.6% (73/78) of injected lesions and 79.0% (94/119) of non-injected lesions

The kinetics of response were similar in injected vs non-injected lesions (Figure 2)

Of the non-injected visceral lesions in responding patients, 96.2% (50/52) showed reduction from baseline, with 65.4% reduced by ≥30% (Figure 3)

Cowey CL, et al. Medicine. 2019;98:28(e16328).

Patrinely JR, et al. Cancer. 2020;126(15):3448-55.

Ribas A, et al. Lancet Oncol. 2018;19(5):e219.

Pires da Silva I, et al. Lancet Oncol. 2021;22:836-47.

14. Thomas S, et al. J Immunother Cancer. 2019;7(1):214. like to thank the site staff and principal investigators for their critical contributions to this study. Medical writing

and editorial support were provided by June F. Yang, PhD, of Red Nucleus and funded by Replimune, Inc.

RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

Nivolumab was supplied by Bristol Myers Squibb. are for personal use only and may not be reproduced without

8. Nordstrom BL, et al. Future Oncol. 2022;18(11):1343-55. 12. Ascierto PA, et al. J Clin Oncol. 2023;41:2724-35.

Contact: [email protected]

Baseline

2 months

20.5 months

52 lung injections

in 7 patients

Pneumothorax events: 3/52 (5.8%)

Grade 1: 1/52 (1.9%)

Grade 2: 2/52 (3.8%)

Grade ≥3: 0

Injected Non-injected

Management of pneumothorax

Grade 1 pneumothorax

No treatment was required

The event resolved after 13 days

Grade 2 pneumothorax

The patient underwent a chest X-ray and received an opioid analgesic

The event resolved on the same day

Grade 2 pneumothorax (prior patient example)

The patient was treated with chest tube insertion, oxygen therapy, an analgesic, an opioid analgesic, and a NSAID

The event resolved after 4 days

The patient continued to receive lung injections without recurrence of pneumothorax

Table 2. Responses in injected vs non-injected lesions from RECIST 1.1 responders (lesion-level data)

Number (%) of measured lesions for RECIST 1.1 responders (CR or PR; N = 46)

Injected lesions

(n = 78)

Non-injected lesions

(n = 119)

Number (%) of lesions with

No reduction

1 (1.3)

4 (3.4)

Any reduction

77 (98.7)

115 (96.6)

Best reduction ≥0% to <30%

4 (5.1)

21 (17.6)

Best reduction ≥30% to <100%

31 (39.7)

47 (39.5)

Best reduction of 100%

42 (53.8)

47 (39.5)

BICR, blinded independent central review; BOR, best overall response; CR, complete response; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease.

RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

TRAE, treatment-related adverse event.

Screening

RP1

*First dose = 106 PFU/mL

**Subsequent doses = 107 PFU/mL

Nivo

†240 mg (Q2W) for 8 cycles

‡480 mg (Q4W) for 21 cycles

Key eligibility

Anti-PD-1-failed advanced melanoma; measurable disease; adequate organ function; no prior oncolytic therapy; ECOG performance status 0-1

Primary Objective

Safety and efficacy using mRECISTc

by BICR (also assessed by RECIST 1.1)

Secondary Objectives

ORR by investigator assessment (mRECISTc)

DOR, CR rate, and PFS by central and investigator assessment, 1-year and 2-year OS

The IGNYTE study is currently recruiting patients with anti-PD-1-failed NMSC and

References:

Acknowledgments:

Disclosures:

Disclaimer:

anti-PD-1-failed MSI-H/dMMR solid tumors. To learn more about enrolling your patient,

1. Robert C, et al. N Eng J Med. 2015;372:2521-32.

5. Thakker S, et al. Oncologist. 2024;29:e1783-5.

9. Dixon-Douglas JR, et al. Curr Oncol Rep. 2022;24:1071-9. 13. Sarnaik AA, et al. J Clin Oncol. 2021;39:2656-66.

The authors thank the patients for their participation in the trial, as well as their family members. We would also

This study was funded by Replimune, Inc.

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Disclaimer

Replimune Group Inc. published this content on June 01, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on June 02, 2025 at 00:48 UTC.