sturlimogene erparepvec (RP2) / Replimune - LARVOL DELTA

A multicenter, open-label study of RP2 oncolytic immunotherapy expressing anti–CTLA-4 in combination with second-line atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (HCC) or in combination with first-line durvalumab in advanced biliary tract cancer (BTC). (ASCO-GI 2026) - P2 | "Funded by Replimune, Inc., Woburn, MA, USA Clinical Trial Registration Number: NCT05733598 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • Metastases • Oncolytic virus • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

RP2 (GlobeNewswire) - "The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD-1/PD-L1 progressed hepatocellular carcinoma is currently enrolling. The protocol is being amended to include RP2 as monotherapy with data planned by the end of 2026. The trial is being conducted under a collaboration and supply agreement with Roche. The Company also expects to enroll its first patient in the fourth quarter of 2025 in a cohort evaluating RP2 in patients with biliary tract cancer. This cohort will evaluate RP2 combined with durvalumab."

P2 data • Trial status • Biliary Tract Cancer • Hepatocellular Cancer

RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Study of RP2 in Combination With Second-line Therapy in Patients With Locally Advanced or Metastatic HCC (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Replimune Inc. | N=30 ➔ 60

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Oncology • Solid Tumor

Replimune Reports Fiscal First Quarter 2026 Financial Results and Provides Corporate Update (The Manila Times) - "RP2 in hepatocellular carcinoma (HCC): The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is currently enrolling with data anticipated in the first half of 2026. This trial will evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab and is expected to enroll 30 patients....RP2 in biliary tract cancer (BTC): As previously reported, the Company expects to dose its first patient in the second half of 2025 in a cohort evaluating RP2 in patients with biliary tract cancer. This trial will evaluate RP2 combined with durvalumab and is expected to enroll 30 patients."

New trial • P2 data • Biliary Tract Cancer • Hepatocellular Cancer

RPx: A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 (clinicaltrials.gov) - P=N/A | N=50 | Not yet recruiting | Sponsor: Replimune Inc. | Initiation date: Jun 2025 ➔ Nov 2025

Trial initiation date • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine

New P2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor-naïve patients with metastatic uveal melanoma. (ASCO 2025) - P2/3 | "Tebentafusp is FDA approved for mUM based on survival benefit; however, its use is restricted to pts who are HLA-A*02:01 positive, and only ~10% of pts achieve an objective response. The co-primary endpoints are OS and progression-free survival by independent central review using RECIST 1.1. Secondary endpoints are overall response rate, duration of response, disease control rate, clinical benefit rate, duration of clinical benefit, and safety, including incidence of treatment-emergent adverse events (AEs), serious AEs, and immune-mediated AEs."

Checkpoint inhibition • Clinical • Metastases • P2/3 data • Eye Cancer • Herpes Simplex • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CSF2 • HLA-A

Replimune Reports Fiscal Fourth Quarter and Year End 2025 Financial Results and Provides Corporate Update (TradingView) - "RP2 in uveal melanoma: The registration-directed REVEAL trial of RP2 in metastatic uveal melanoma is currently enrolling. The clinical trial is expected to enroll approximately 280 patients with metastatic uveal melanoma who are immune checkpoint inhibitor-naïve and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab....RP2 in hepatocellular carcinoma (HCC): The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is currently enrolling. The clinical trial will evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab and is expected to enroll 30 patients."

Trial status • Hepatocellular Cancer • Uveal Melanoma

INTERCEPT: Phase II Study of RP2 as Immunoprevention in High-Risk Oral Precancerous Disease (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Glenn J. Hanna | Trial completion date: Jan 2028 ➔ Jan 2029 | Trial primary completion date: Jan 2026 ➔ Jan 2027 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Oncology • Oral Cancer

RPx: A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 (clinicaltrials.gov) - P=N/A | N=50 | Not yet recruiting | Sponsor: Replimune Inc.

New trial • Hepatocellular Cancer • Hepatology • Melanoma • Oncology • Solid Tumor

Replimune Reports Fiscal Third Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Completed a public offering of shares of the Company’s common stock and pre-funded warrants, raising approximately $156.0 million net of issuance costs. Proceeds from the financing will be used to fund the continued development of our RPx platform, including expanding our ongoing studies within RP1 and broadening clinical development plans for RP2...Research and development expenses were $48.0 million for the fiscal third quarter ended December 31, 2024, as compared to $42.8 million for the fiscal third quarter ended December 31, 2023."

Financing • Hepatocellular Cancer • Melanoma • Uveal Melanoma

A multicenter, open-label study investigating RP2 oncolytic immunotherapy in combination with second-line systemic atezolizumab plus bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma (HCC). (ASCO-GI 2025) - P2 | "The primary endpoint is overall response rate (ORR), defined as the proportion of pts achieving a best overall response of complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as modified for this study. Secondary endpoints include safety, ORR using HCC-modified RECIST, duration of response, complete response rate, and progression-free survival."

Clinical • Combination therapy • IO biomarker • Metastases • Oncolytic virus • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CSF2

Replimune Announces RP2 Development Program Advances with First Patients Enrolled in Metastatic Uveal Melanoma and Hepatocellular Carcinoma Clinical Trials (GlobeNewswire) - "Replimune Group, Inc...announced that the first patients have been enrolled in studies evaluating RP2 in two different settings: checkpoint naïve metastatic uveal melanoma; and second-line recurrent or metastatic hepatocellular carcinoma (HCC)....The RP2-202 trial (NCT06581406) is a randomized, phase 2/3 study that will enroll approximately 280 patients and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab in immune checkpoint inhibitor-naïve adult patients with metastatic uveal melanoma....The RP2-003 trial (NCT05733598) is an open label trial that will enroll 30 patients and evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab in patients with locally advanced unresectable, recurrent and/or metastatic HCC."

Enrollment open • Hepatocellular Cancer • Uveal Melanoma

New Funding Awards October 2024 (Duke University School of Medicine) - "April Salama of Oncology has received an award from Replimune, Inc. for a project entitled 'Replimune RP2-202: 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-Naive Adult Patients with Inoperab.' Total funding will be $828,581....Mitchell Horwitz of Cell Therapy has received an award (2UG1-HL069274-24) from the National Institutes of Health for a project entitled 'Blood and Marrow Transplant Clinical Trials Network.' Total funding will be $1,199,830."

Grant

Replimune Reports Fiscal Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Study start-up activities are underway for a registration-directed study of RP2 in metastatic uveal melanoma in patients who are immune checkpoints inhibitor-naïve. The study plans to enroll the first patient in a randomized trial of RP2 in combination with nivolumab vs. ipilimumab and nivolumab, or nivolumab for those ineligible for ipilimumab in the first quarter of 2025...A Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is actively screening patients...As of September 30, 2024, cash, cash equivalents and short-term investments were $432.1 million....Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of September 30, 2024 will enable the Company to fund operations into the second half of 2026 which includes scale up for the commercialization of RP1 in skin cancers and for working capital and general corporate purposes."

Commercial • Trial status • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Skin Cancer • Solid Tumor • Uveal Melanoma

RP2-202: 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 (clinicaltrials.gov) - P2/3 | N=280 | Recruiting | Sponsor: Replimune Inc. | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Combination therapy • Enrollment open • Metastases • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Study of RP2 in Combination With Second-line Therapy in Patients With Locally Advanced Unresectable or Metastatic HCC (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Replimune Inc. | Not yet recruiting ➔ Recruiting | N=60 ➔ 30 | Trial completion date: Jul 2027 ➔ Jul 2028 | Trial primary completion date: Apr 2027 ➔ Dec 2027

Combination therapy • Enrollment change • Enrollment open • Metastases • Oncolytic virus • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

INTERCEPT: Phase II Study of RP2 As Immunoprevention in High-Risk Oral Precancerous Disease (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Glenn J. Hanna

New P2 trial • Oncology • Oral Cancer

RP2-202: 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 (clinicaltrials.gov) - P2/3 | N=280 | Not yet recruiting | Sponsor: Replimune Inc.

Checkpoint inhibition • Combination therapy • Metastases • New P2/3 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Replimune Reports Fiscal First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "RP2 in Hepatocellular Carcinoma (HCC): A Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is expected to dose its first patient in 2H 2024."

Trial status • Hepatocellular Cancer • Liver Cancer

An open-label, multicenter study investigating RP2 oncolytic immunotherapy in combination with second-line systemic atezolizumab combined with bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma. (ASCO 2024) - P2 | "The primary endpoint is overall response rate (ORR), defined as the proportion of pts achieving a best overall response of complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as modified for this study. Secondary endpoints are safety, ORR using HCC-modified RECIST, duration of response, complete response rate, and progression-free survival."

Clinical • Combination therapy • Metastases • Oncolytic virus • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Malignancies • Hepatocellular Cancer • Herpes Simplex • Leukemia • Oncology • Solid Tumor • CSF2

Safety, efficacy, and biomarker results from an open-label, multicenter, phase 1 study of RP2 alone or combined with nivolumab in a cohort of patients with uveal melanoma. (ASCO 2024) - P1 | "RP2 alone or combined with nivo demonstrated a favorable safety profile and meaningful antitumor activity in pts with previously treated MUM. Biomarker data indicated immune cell infiltration and increased PD-L1 expression in tumors and changes in the peripheral T-cell repertoire following RP2 ± nivo therapy. Based on these results, a randomized, controlled clinical development plan is being planned."

Biomarker • Clinical • IO biomarker • P1 data • Dermatology • Eye Cancer • Fatigue • Genito-urinary Cancer • Hypotension • Melanoma • Oncology • Pruritus • Solid Tumor • Uveal Melanoma • CD8 • PD-L1

Replimune Presents Positive Data from RP1 and RP2 Clinical Programs at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1 | N=36 | NCT04336241 | Sponsor: Replimune Inc. | "Replimune Group...presented two oral presentations highlighting promising clinical data from its RP1 and RP2 programs at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....The data suggest that RP2, which expresses an anti-CTLA-4 antibody, dosed both alone and in combination with an anti-PD-1 agent in metastatic uveal melanoma patients (n=17), including those with both liver and extra-hepatic metastases, had a favorable safety profile and durable anti-tumor activity. RP2 administered as monotherapy or in combination with nivolumab demonstrated an ORR of 29.4%, with a disease control rate (DCR) of 58.8%. Biomarker data indicate immune cell infiltration and increased PD-L1 expression in tumors, together with changes in the systemic T cell repertoire following RP2 plus nivolumab."

Biomarker • P1 data • Uveal Melanoma

Replimune to Present at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Replimune Group Inc...announced multiple presentations at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago from May 31-June 4, 2024....The Company has two abstracts selected for oral presentation, including an updated presentation of investigator-assessed 12-month data from the IGNYTE clinical trial of RP1 (vusolimogene oderparepvec) plus nivolumab in anti-PD-1 failed melanoma, and another presentation showcasing data from the Phase 1 trial of RP2 combined with nivolumab in advanced uveal melanoma. In addition, RP1 and RP2 are also featured in three trial-in-progress posters."

Clinical data • Trial status • Eye Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Uveal Melanoma