RP2

Sturlimogene erparepvec

DEVELOPMENT STEP phase-2

MECHANISM TARGET // UNMAPPED_TARGET

[THERAPEUTIC_PROFILE]

Target Indications

Metastatic Uveal Melanoma, Hepatocellular Carcinoma

Mechanism Abstract

A genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, expressing the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and an antibody-like molecule directed against the human inhibitory T-cell-expressed receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4;CTLA4), with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, sturlimogene erparepvec specifically infects and replicates in tumor cells causing viral-mediated tumor cell lysis. The released virus particles, in turn, infect and replicate in neighboring tumor cells. Tumor antigens released from the lysed tumor cells also activate the immune system to induce a tumor-specific systemic immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected tumor cells. Sturlimogene erparepvec expresses a fusogenic protein, GALV-GP R-, for optimal tumor cell infection and killing. In addition, this agent promotes the secretion of GM-CSF and anti-CTLA-4 antibody-like molecule by the tumor cells. GM-CSF attracts dendritic cells (DCs) and may further stimulate a CTL-mediated immune response against tumor cells. Anti-CTLA-4 antibody-like molecule targets and binds to CTLA-4 expressed on T cells, and inhibits the CTLA-4-mediated downregulation of T-cell activation. This leads to a CTL-mediated immune response against tumor cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), plays a key role in the downregulation of the immune system.

[3D_INTERACTIVE_CONFORMATION]

 // NO_VALID_STRUCTURAL_ASSET_IDENTIFIERS 

[CLINICAL_TRIALS_REGISTRY]

TOTAL EXTRACTED7

RECRUITING STATUS4

COMPLETED RUNS0

REGISTRY & PHASE

TESTED CONDITION

STUDY TITLE & LIFECYCLE TIMELINES

STATUS

➔

P-2NCT07059611

Gastric AdenocarcinomaEsophageal Adenocarcinoma+1 more

N=34Est. Finish: 2029-11-01

Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma

not yet recruiting

ENROLLMENT PATIENT CAPACITY34 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2026-09-01(estimated)

Primary End:2027-11-01(estimated)

Study Finish:2029-11-01(estimated)

OFFICIAL PROTOCOL TITLE

Phase II Study of Neoadjuvant RP2 in Combination With Preoperative Flot for Patients With Stage II or Higher, Non-metastatic Gastroesophageal Adenocarcinoma

[INVESTIGATORS_&_FACILITY_ROSTER]

William Chapin, MD, MSCEPRINCIPAL INVESTIGATOR — Abramson Cancer Center at the University of Pennsylvania

Jennifer WalshCONTACT — Abramson Cancer Center at the University of Pennsylvania

Jennifer Eads, MDCONTACT — Abramson Cancer Center at Penn Medicine

[PRIMARY_SUCCESS_ENDPOINTS]

Pathologic complete response

Analysis Window: Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.

[SECONDARY_SUCCESS_ENDPOINTS]

Adverse event profile

Analysis Window: The adverse event reporting period first RP2 intratumoral injection until 30 days post-surgical resection or 56 days after the last administration of RP2 (if no resection or or consent withdrawal).

R0 resection rate

Disease-free Survival (DFS)

Analysis Window: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.

Overall Survival (OS)

Analysis Window: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

RP2 and FLOT

EXPERIMENTAL

No descriptive logs found.

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2BIOLOGICAL

Upper endoscopy with RP2 intra-tumoral injection of 1 x 10(6) plaque forming units (PFU)/mL for first intra-tumoral injection, up to 10mL of 1x107 PFU/mL of RP2 for subsequent intra-tumoral injections. Injection will occur within 4 days prior of each cycle FLOT.

5-FluorouracilCOMBINATION_PRODUCT

5-Fluorouracil as part of the FLOT regimen 2,600mg/m2 intravenous infusion over 24 hours on day 1 of each 14-day cycle for 4 cycles.

LeucovorinCOMBINATION_PRODUCT

Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

OxaliplatinCOMBINATION_PRODUCT

Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

DocetaxelCOMBINATION_PRODUCT

Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

PegfilgrastimDRUG

Pegfilgrastim or Filgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

FilgrastimDRUG

Filgrastim or Pegfilgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

Surgical Resection of Primary TumorPROCEDURE

Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.

➔

P-2NCT05733598

Hepatocellular CarcinomaBiliary Tract Cancer

N=60Est. Finish: 2028-07-01

Study of RP2 in Combination With Second-line Therapy in Patients With Locally Advanced or Metastatic HCC

recruiting

ENROLLMENT PATIENT CAPACITY60 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2024-08-01(actual)

Primary End:2027-12-01(estimated)

Study Finish:2028-07-01(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 2, Open-label, Multicenter Study Investigating RP2 Oncolytic Immunotherapy in Combination With Second-line Therapy in Patients With Locally Advanced Unresectable, Recurrent and/or Metastatic Hepatocellular Carcinoma

[INVESTIGATORS_&_FACILITY_ROSTER]

Gary Vanasse, MDSTUDY DIRECTOR — Replimune, Inc.

Afshin Eli Gabayan, MDCONTACT — Beverly Hills Cancer Center

Adam Burgoyne, MDCONTACT — UC San Diego Moores Cancer Center

Lynn Goy Feun, MDCONTACT — Sylvester Comprehensive Cancer Center (University of Miami Hospital and Clinics)

Richard Kim, MDCONTACT — Moffitt Cancer Center

Kevin"Hyun" Kim, MDCONTACT — University of Maryland Medical Center

Renuka Iyer, MDCONTACT — Roswell Park Comprehensive Cancer Center

Yvonne Saenger,, MDCONTACT — Montefiore Medical CenterMontefiore Medical Park

William Chapin, MDCONTACT — University of Pennsylvania, Abramson Cancer Center

Anwaar Saeed, MD.CONTACT — UPMC Hillman Cancer Center

+3 more registered trial investigators

[PRIMARY_SUCCESS_ENDPOINTS]

Overall Response Rate per modified RECIST 1.1

Analysis Window: From Day 1 up to 3 years after first RP2 dose of last patient.

[SECONDARY_SUCCESS_ENDPOINTS]

Number of patients with treatment-emergent adverse events (TEAEs)

Analysis Window: From Day 1 up to 135 days after last dose.

ORR per RECIST modified for HCC (HCC mRECIST) for HCC cohort only

Analysis Window: From Day 1 up to 3 years after first RP2 dose of last patient

Duration of response (DOR)

Analysis Window: From Day 1 up to 3 years after first RP2 dose of last patient.

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

RP2+Bevacizumab and Atezolizumab

EXPERIMENTAL

HCC Cohort 1a and 1b: Patients with locally advanced unresectable, recurrent and/or metastatic HCC who have progressed on 1 prior systemic treatment, which must have included anti-programmed cell death 1 (PD-1)/anti-PD-L1 therapy. Patients will receive atezolizumab plus bevacizumab therapy combined with RP2. In cohort 1a, patients will receive RP2 intratumorally every 2 weeks (Q2W) for 4 doses, then every 3 weeks (Q3W) for 4 doses combined with atezolizumab plus bevacizumab. In cohort 1b, patients will receive RP2 intratumorally every 2 weeks (Q2W) for 8 doses combined with atezolizumab plus bevacizumab.

RP2 Monotherapy

EXPERIMENTAL

HCC Cohort 2: Patients with locally advanced unresectable, recurrent and/or metastatic HCC who have progressed on 1 prior systemic treatment, which must have included anti-programmed cell death 1 (PD-1)/anti-PD-L1 therapy. Patients will receive RP2 monotherapy every 2 weeks (Q2W).

RP2+Durvalumab

EXPERIMENTAL

BTC Cohort (Cohort 3): Patients with locally advanced or metastatic BTC (intrahepatic or extrahepatic cholangiocarcinoma or gall bladder carcinoma), who have received treatment with combination gemcitabine, platinum-containing chemotherapy, and checkpoint inhibitor for a minimum of 12 weeks (4 to 8 cycles) and maximum of 24 weeks, and who have had stable disease or partial response on 2 on treatment scans and no progressive disease. After the last combination chemotherapy treatment, checkpoint inhibitor treatment must be limited to 2 doses (8 weeks). Patients will receive durvalumab combined with RP2.

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2BIOLOGICAL

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.

BevacizumabBIOLOGICAL

Anti-VEGF therapy.

AtezolizumabBIOLOGICAL

Anti-PD-L1 monoclonal antibody.

DurvalumabBIOLOGICAL

Anti-PD-L1 monoclonal antibody

RP2 MonotherapyBIOLOGICAL

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.

➔

P-2NCT06581406

Metastatic Uveal Melanoma

N=280Est. Finish: 2031-10

A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma

recruiting

ENROLLMENT PATIENT CAPACITY280 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2024-12-17(actual)

Primary End:2030-01(estimated)

Study Finish:2031-10(estimated)

OFFICIAL PROTOCOL TITLE

A Randomized, Phase 2/3, Open-Label Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab Versus Ipilimumab in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma

[INVESTIGATORS_&_FACILITY_ROSTER]

Rahul Marpadga, MD MPHSTUDY DIRECTOR — Replimune, Inc.

Justin Moser, MDCONTACT — HonorHealth Research Insisute

Gregory Daniels, MDCONTACT — UC San Diego Moores Cancer Center

Inderjit Mehmi, MDCONTACT — The Angeles Clinic and Research Institute

Bartosz Chmielowski, MDCONTACT — University of California Los Angeles

Allison Betof Warner, MDCONTACT — Stanford Cancer Institute

Sapna Pradyuman Patel, MDCONTACT — University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Ryan Weight, DO, MSCONTACT — The Melanoma & Skin Cancer Institute

Suthee Rapisuwon, MDCONTACT — Georgetown University Medical Center

Roxana S. Dronca, MDCONTACT — Mayo Clinic - Jacksonville FL

+25 more registered trial investigators

[PRIMARY_SUCCESS_ENDPOINTS]

Overall Survival (OS)

Analysis Window: From Day 1 up to 3 years after last dose.

Progression Free Survival (PFS)

Analysis Window: From Day 1 up to 3 years after last dose.

[SECONDARY_SUCCESS_ENDPOINTS]

Number of patients with treatment-emergent adverse events (TEAEs)

Analysis Window: From first dose up to 100 days after last dose.

Overall Response Rate (ORR)

Analysis Window: Every 12 weeks from Day 1 up to 3 years after last dose.

Disease Control Rate (DCR)

Analysis Window: Every 12 weeks from Day 1 up to 3 years after last dose.

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Test Arm: RP2 + nivolumab

EXPERIMENTAL

RP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor)

Control Arm (Active Comparator): ipilimumab + nivolumab

EXPERIMENTAL

Immune Checkpoint inhibitor combination

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2BIOLOGICAL

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.

IpilimumabBIOLOGICAL

Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody

NivolumabBIOLOGICAL

Nivolumab: Anti-PD-1 Monoclonal antibody

➔

P-2NCT05733611

Refractory Metastatic Colorectal CancerpMMR+1 more

N=5Est. Finish: 2025-08-18

RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC

terminated

ENROLLMENT PATIENT CAPACITY5 Patients(actual)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2023-06-29(actual)

Primary End:2025-08-18(actual)

Study Finish:2025-08-18(actual)

OFFICIAL PROTOCOL TITLE

A Phase 2 Clinical Trial Investigating Oncolytic Immunotherapy in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With Advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma

[INVESTIGATORS_&_FACILITY_ROSTER]

Gary Vanasse, MDSTUDY DIRECTOR — Replimune, Inc.

[PRIMARY_SUCCESS_ENDPOINTS]

Objective Response Rate (ORR)

Analysis Window: From Day 1 to documented progression of disease (up to 3 years)

[SECONDARY_SUCCESS_ENDPOINTS]

Frequency, Nature, and Severity of TEAEs and SAEs

Analysis Window: From Screening through 60 days after last dose of RP2/RP3, or 135 days after last dose of atezolizumab/bevacizumab

Overall Survival

Analysis Window: From Day 1 to date of death by any cause (up to 3 years)

Progression-free Survival

Analysis Window: From Day 1 to documented progression of disease (up to 3 years)

Duration of Response

Analysis Window: From documented response to documented progression of disease (up to 3 years)

Duration of Clinical Benefit

Analysis Window: From Day 1 to loss of clinical benefit (up to 3 years)

Complete Response Rate

Analysis Window: From Day 1 to documented progression of disease (up to 3 years)

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

EXPERIMENTAL

RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

EXPERIMENTAL

RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2BIOLOGICAL

Genetically modified herpes simplex type 1 virus

RP3BIOLOGICAL

Genetically modified herpes simplex type 1 virus

atezolizumabBIOLOGICAL

anti-PD-L1 monoclonal antibody

bevacizumabBIOLOGICAL

anti-VEGF therapy

➔

P-2NCT06623110

High-Risk Oral Precancerous Disease

N=25Est. Finish: 2029-01-01

Phase II Study of RP2 as Immunoprevention in High-Risk Oral Precancerous Disease

recruiting

ENROLLMENT PATIENT CAPACITY25 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2025-01-01(actual)

Primary End:2027-01-01(estimated)

Study Finish:2029-01-01(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 2 Study of Intralesional RP2 as Immunoprevention for High-Risk Oral Precancerous Disease (INTERCEPT)

[INVESTIGATORS_&_FACILITY_ROSTER]

Glenn Hanna, MDPRINCIPAL INVESTIGATOR — Dana-Farber Cancer Institute

Glenn J Hanna, MDCONTACT — Brigham and Women's Hospital

[PRIMARY_SUCCESS_ENDPOINTS]

Best Overall Response

Analysis Window: Up to 1 year

[SECONDARY_SUCCESS_ENDPOINTS]

Adverse Event Rate

Analysis Window: Up to 1 year

Median Cancer-free Survival (CFS)

Analysis Window: Up to 1 year

Median Overall Survival (OS)

Analysis Window: Up to 3 years

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

RP2 Injection

EXPERIMENTAL

Enrolled participants will complete the following: * A 3 subject safety run-in will be conducted with participants enrollment staggered. If \> 1 subject experiences a grade 4-5 adverse event (AE), study enrollment will pause for review by PI and study sponsor. If there are 0 grade 4-5 AEs, enrollment will proceed. * Baseline in-clinic visit with assessments, oral mucosal punch biopsy, and RP2 injection (week 1). * In-clinic visits on weeks 3, 5, 7, 8, 9, 11, 13, 15, and 16. * RP2 injections on weeks 1, 3, 5, 7, 9, 11, 13, and 15. * Repeat oral mucosal punch biopsy at week 8. * Follow up: every 3 months for up to 2 years.

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2 InjectionBIOLOGICAL

Genetically modified live HSV-1 virus, 3.0 mL single-use glass vials, via intralesional (into a lesion) injection per protocol.

➔

P-1NCT04336241

Cancer

N=36Est. Finish: 2026-10-31

Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors

active not recruiting

ENROLLMENT PATIENT CAPACITY36 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2019-10-17(actual)

Primary End:2026-10-31(estimated)

Study Finish:2026-10-31(estimated)

OFFICIAL PROTOCOL TITLE

An Open-Label, Multicenter, Phase 1 Study of RP2 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors

[INVESTIGATORS_&_FACILITY_ROSTER]

Gary Vanasse, MDSTUDY DIRECTOR — Replimune, Inc.

[PRIMARY_SUCCESS_ENDPOINTS]

Percentage of adverse events (AEs)

Analysis Window: From Day 1 up to 60 days after last dose

Percentage of serious adverse events (SAEs)

Analysis Window: From Day 1 up to 60 days after last dose

Percentage of dose limiting toxicities (DLTs)

Analysis Window: From Day 1 up to 30 days after last dose.

Percentage of treatment emergent adverse events (TEAEs)

Analysis Window: From Day 1 up to 60 days after last dose.

[SECONDARY_SUCCESS_ENDPOINTS]

Percentage of biologic activity

Analysis Window: 20 weeks

Percentage of subjects with detectable RP2

Analysis Window: 20 weeks

Change in HSV-1 antibody levels

Analysis Window: From Day 1 up to last dose (up to 4 months for dose escalation phase and up to 5.5 months for expansion phase)).

Percentage of overall response rate (ORR)

Analysis Window: 3 years

Median duration of response

Analysis Window: 3 years

Median progression-free survival

Analysis Window: 3 years

Median overall survival

Analysis Window: 3 years

Percentage of complete response (CR)

Analysis Window: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Dose escalation of RP2 - superficial tumors

EXPERIMENTAL

Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors.

Dose escalation of RP2 - deep/visceral tumors

EXPERIMENTAL

Dose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors.

Dose expansion of RP2 and nivolumab - superficial tumors

EXPERIMENTAL

Doses of RP2 (IT) in superficial tumors with nivolumab (IV).

Dose expansion of RP2 and nivolumab - deep/visceral tumors

EXPERIMENTAL

Imaging guided doses of RP2 (IT) in deep/visceral tumors.

Seronegative cohort

EXPERIMENTAL

Doses of RP2 (IT) in HSV seronegative participants.

[DOSING_&_INTERVENTION_SPECIFICITIES]

RP2BIOLOGICAL

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

nivolumabBIOLOGICAL

Programmed death receptor (PD-1) blocking antibody

➔

P-N/ANCT06887348

MelanomaMetastatic Melanoma+2 more

N=50Est. Finish: 2035-12

A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3

recruiting

ENROLLMENT PATIENT CAPACITY50 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2025-12-12(actual)

Primary End:2030-12(estimated)

Study Finish:2035-12(estimated)

OFFICIAL PROTOCOL TITLE

Long-term Safety Outcomes in Patients Treated With Replimune Oncolytic Immunotherapy Products

[INVESTIGATORS_&_FACILITY_ROSTER]

Soo Park, MDPRINCIPAL INVESTIGATOR — UC San Diego Moores Cancer Center

Andrew Hill, MDPRINCIPAL INVESTIGATOR — Tasman Oncology Research

[PRIMARY_SUCCESS_ENDPOINTS]

Evaluate the long-term safety of patients treated with an RPx product

Analysis Window: Every 3 months (Q3M) (± 30 days) for 5 years from enrollment on this study to assess potential delayed risks

Identify any delayed adverse event(s) related to treatment with an RPx product

Analysis Window: Every 3 months (Q3M) (± 30 days) for 5 years from enrollment on this study to assess potential delayed risks

Identify systemic HSV-1 infection related to treatment with an RPx product

Analysis Window: Every 3 months (Q3M) (± 30 days) for 5 years from enrollment on this study to assess potential delayed risks

[SECONDARY_SUCCESS_ENDPOINTS]

// NO_EXPLICIT_SECONDARY_OUTCOMES_DUMPED

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Patients who received at least 1 dose of an RPx [RP1, RP2, RP3]

N/A

This is an observational study and there will be no clinical interventions.

[DOSING_&_INTERVENTION_SPECIFICITIES]

Observational study with no interventionsOTHER

This is an observational study and there will be no clinical interventions.

[BIOCHEMICAL_STRUCTURE_REGISTRY]

// SYSTEM_REGISTRY_LOG: PUBCHEM_SID_REJECTION_ERR_503 (Input: "518034848")