Intratumoral Vusolimogene Oderparepvec (VO) in Combination With Pembrolizumab for Angiosarcoma

NCT06898970 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 25871NCI-2025-02056
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label study of Intratumoral Vusolimogene Oderparepvec (VO) to investigate safety and estimate when used in combination with pembrolizumab for treating participants with angiosarcoma. This is the first study evaluating this novel combination in participants with advanced angiosarcoma who have progressed after prior immunotherapy.

Conditions

Angiosarcoma; Angiosarcoma, Adult

Keywords

Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Percentage of participants with reported treatment-emergent adverse events (Safety Lead-In)

  Safety and tolerability will be reported as the percentage of the first 6 participants (the safety-lead in participants) who received at least one dose of study treatment with any reported treatment-emergent adverse events (TEAEs), \>= Grade 3 TEAEs, serious adverse events (SAEs), and TEAEs requiring discontinuation of VO. Adverse events will be classified using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 1 year

• Proportion of participants who experience an objective response (Phase 2 participants)

  Objective response will be measured per RECIST v. 1.1 and is defined as complete response (CR) or partial response (PR) and confirmed by repeat imaging \>=4 weeks after assessment for participants who completed at least 4 of the planned 8 intratumoral injections.

  Up to 1 year

• Percentage of participants with reported treatment-emergent adverse events

  The percentage of all participants who received at least one dose of study treatment with any treatment-emergent adverse events (TEAEs), ≥ Grade 3 TEAEs, serious adverse events (SAEs), and TEAEs requiring discontinuation of VO. Adverse events will be classified using NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.

  Up to 1 year

Secondary Outcomes (6)

• Median Duration of Response (DOR)

  Up to 1 year

• Percentage of participants with documented Complete Response (CRR)

  Up to 1 year

• Percentage of participants with documented Clinical Benefit (CBR)

  Up to 1 year

• Median Progression-Free Survival (PFS)

  Up to 2 years

• Median Overall Survival

  Up to 2 years

Study Arms (1)

Treatment (Vusolimogene Oderparepvec (VO), Pembrolizumab)

EXPERIMENTAL

All participants receive a single dose of VO on Day -14. On Cycle 1 Day 1 (C1D1), participants receive second dose of VO, and subsequent doses occur every 3 weeks for 7 cycles in combination with 200 mg pembrolizumab every 3 weeks for 8 cycles starting C1D1. After 8 cycles of pembrolizumab, participants may have the pembrolizumab dose schedule altered to a single 400 mg dose every 6 weeks, and treatment with pembrolizumab may continue for up to 2 years after starting first dose on C1D1. Participants may receive up to eight additional doses of VO after progression for a total of 16 dosing days. Safety follow up visits occur 30 and 90 days after last dose of either treatment (whichever drug was taken last) or after the participant has taken 2 years of pembrolizumab as a part of this study.

Biological: Vusolimogene Oderparepvec (VO); Drug: Pembrolizumab

Interventions

Vusolimogene Oderparepvec (VO) BIOLOGICAL

Given intratumorally

Also known as: RP1

Treatment (Vusolimogene Oderparepvec (VO), Pembrolizumab)

Pembrolizumab DRUG

Given IV

Also known as: Keytruda

Treatment (Vusolimogene Oderparepvec (VO), Pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with biopsy proven cutaneous angiosarcoma that is locally advanced and unresectable or metastatic and has received and progressed on at least one prior immunotherapy based regimen within 6 months prior to screening.
• At least one measurable tumor of ≥ 1 cm in longest diameter or ≥ 1.5 cm in shortest diameter (for lymph nodes) and injectable lesions which in aggregate comprise \>= 1 cm in longest diameter.
• Participants must have received and progressed following first-line standard of care, including a taxane or anthracycline based chemotherapy regimen.
• Measurable disease based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Life expectancy of at least 3 months, in the opinion of the treating investigator.
• Females of childbearing potential must have a negative beta-human chorionic gonadotropin (beta-hCG) test at screening within 7 days of Cycle 1 Day 1.
• Female participants of reproductive potential must agree to avoid becoming pregnant and adhere to a highly effective contraception method until 90 days after last dose of VO alone or 120 days after last dose of VO and pembrolizumab.
• Male participants of reproductive potential must agree to avoid impregnating a partner and adhere to a highly effective contraception method until 90 days after last dose of VO study agent and refrain from donating sperm during this period.
• Age \<=18 years on the day of signed informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky ≥ 70%)
• Adequate hematologic function including:
• White blood cell count (WBC) \>= 2.0 × 109/L
• Absolute neutrophil count (ANC) \>= 1.5 × 109/L
• Platelet count \>=100 × 109/L
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks of dosing)

You may not qualify if:

• Prior treatment with an oncolytic therapy.
• Currently receiving antiviral drug therapy (e.g. valacyclovir or acyclovir).
• Has acute or chronic active hepatitis B and C virus infection or known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA \[qualitative\]) or HIV infection.Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or if clinically indicated.
• Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
• Has active significant herpetic infections or prior complications of herpes simplex 1 (HSV-1) infection (e.g., herpetic keratitis or encephalitis).
• Systemic anticancer therapy within 4 weeks prior to enrollment or five half-lives, whichever is shorter, before the first administration of VO. Note: programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) directed therapy is allowed.
• Has not recovered from adverse events due to prior anti-cancer therapy to \<= grade 1 or baseline. Note: participants with toxicities after prior anticancer therapies that are not considered a likely safety risk such as Grade ≤ 2 neuropathy or alopecia, or immune mediated AEs that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis, stable endocrine insufficiencies such as thyroid and adrenal insufficiency), are an exception to this criterion and may qualify for the study in discussion with the Principal Investigator.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within four weeks prior to the first dose of study treatment. Note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been four weeks since the last dose of the previous investigational agent.
• Has received prior radiotherapy within two weeks of start of study treatment. Note: participants who are eligible must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-CNS disease.
• History of interstitial lung disease.
• History of documented allergic reactions or acute hypersensitivity attributed to VO and pembrolizumab or any of its excipients.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Available Coronavirus disease of 2019 (COVID-19) vaccines do not contain live virus and are allowed.
• Conditions requiring treatment with immunosuppressive doses (\> 10 mg daily prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment. For the definition of replacement therapy.
• Undergo major surgery ≤ 2 weeks prior to starting VO. Note: participants who undergo major surgery requiring general anesthesia such as exploratory laparotomy or thoracotomy and are eligible for the study must adequately recover prior to starting study treatment. Procedures such as central line placement, endoscopies and tooth extractions under local anesthesia do not meet criteria for major surgery.
• Has a history of (non-infectious) pneumonitis that required corticosteroids or has current pneumonitis.

Sponsors & Collaborators

• Varun Monga, MBBS: lead
• Replimune Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Hemangiosarcoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Study Officials

• Varun Monga, MBBS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Tan

CONTACT

(415) 866-7866; Lisa.Tan@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: March 27, 2025
• Study Start: January 9, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)