RP1 for Melanoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Yana Najjar
Must not be taking: Immunosuppressants, Live vaccines
Disqualifiers: Hepatitis, HIV, Herpetic infections, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This early-phase study will examine Vusolimogene Oderparepvec, a genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, vusolimogene oderparepvec specifically targets, infects and replicates in tumor cells and does not infect healthy cells. This results in tumor cell lysis and the release of virus particles which infect and replicate within nearby tumor cells, resulting in tumor cel death. The immune system is activated by the released tumor-associated antigens (TAAs) from the tumor cells creating an anti-tumor immune response against the tumor cells, thereby further killing the tumor cells. The virus itself also elicits a tumor-specific systemic immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected tumor cells.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on immunosuppressive doses of corticosteroids or have received a live vaccine within 30 days before the study starts.
What data supports the effectiveness of the treatment Vusolimogene Oderparepvec (RP1) for melanoma?
Research on a similar treatment, Talimogene laherparepvec (T-VEC), which is also an oncolytic herpes virus encoding GM-CSF, shows it can effectively target melanoma cells, leading to tumor cell death and boosting the immune response. T-VEC has demonstrated promising results in clinical trials, improving response rates and showing potential when combined with other immune therapies.12345
Is RP1 (Vusolimogene Oderparepvec) safe for humans?
The research does not provide specific safety data for RP1 (Vusolimogene Oderparepvec), but it discusses a similar treatment, talimogene laherparepvec, which is a modified herpes virus used for melanoma. This treatment has been approved by the FDA, suggesting it has been evaluated for safety in humans.12678
Eligibility Criteria
This trial is for individuals with primary melanoma, specifically to reduce the risk of cancer spreading to sentinel lymph nodes. Participants must meet certain health criteria not specified here.Inclusion Criteria
I am not pregnant, as confirmed by sensitive blood and urine tests.
I am fully active or restricted in physically strenuous activity but can do light work.
My organ functions are within normal ranges as per recent tests.
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Exclusion Criteria
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
Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study
I haven't taken high doses of steroids, except for replacement therapy, in the last 14 days.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 3 doses of RP1 injected into the skin at the tumor biopsy site at baseline (day 1), day 15, and day 21
4-5 weeks
3 visits (in-person)
Surgery
Definitive surgery including wide local excision and sentinel lymph node biopsy
1 week
Follow-up
Participants are monitored for recurrence of disease and adverse events
Up to 3 years
Treatment Details
Interventions
- Vusolimogene Oderparepvec (RP1) (Virus Therapy)
Trial OverviewThe study tests Vusolimogene Oderparepvec (RP1), a modified herpes virus designed to target and kill melanoma cells while boosting the immune system's response against the tumor.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Vusolimogene oderparepvec (RP1)Experimental Treatment1 Intervention
Patients will receive 3 doses of RP1 (1.0 mL/injection; 10e6 PFU/mL for the first dose, and 10e7 mL for the subsequent 2 doses). The drug will be injected into the skin at the tumor biopsy site at baseline (day 1), day 15, and day 21, 4-5 weeks prior to SOC WLE and SLNB. Definitive surgery will occur up to 28-35 (± 2 days) days from first injection, to avoid treatment delay.
Vusolimogene Oderparepvec (RP1) is already approved in United States for the following indications:
🇺🇸 Approved in United States as RP1 for:
- Advanced melanoma (under review)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Yana NajjarLead Sponsor
Replimune Inc.Industry Sponsor
References
Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. [2021]We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions.
In vitro Characterization of Enhanced Human Immune Responses by GM-CSF Encoding HSV-1-Induced Melanoma Cells. [2022]We studied the innate and adaptive immune response against melanoma cells after JS-1 (wild-type herpes simplex virus 1, wt HSV-1) or Talimogene laherparepvec (T-VEC) infection and evaluated the antitumoral efficacy in human melanoma cells. We analyzed the putative synergistic biological and immunological effects of JS-1 or T-VEC combined with cytostatic drugs in human tumor and immune cells. T-VEC is a genetically modified strain of HSV-1. Genetic modifications (insertion of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene) were made to attenuate the virus and increase selectivity for cancer cells. In addition to the direct oncolytic effect, we investigated the immune stimulatory effects of T-VEC by comparing it with JS-1. JS-1 is identical T-VEC except for the inserted GM-CSF gene.
Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. [2020]Melanoma often spreads to cutaneous or subcutaneous sites that are amenable to direct, intralesional injection. As such, developing effective injectable agents has been of considerable interest. Talimogene laherperepvec (T-VEC) is an injectable modified oncolytic herpes virus being developed for the treatment of advanced melanoma. Pre-clinical studies have shown that T-VEC preferentially infects melanoma cells and exerts antitumor activity through directly mediating cell death and by augmenting local and even distant immune responses. T-VEC has now been assessed in Phase II and III clinical trials and has demonstrated a tolerable side-effect profile and promising efficacy, showing an improved durable response rate and a trend toward superior overall survival compared to granulocyte-macrophage colony-stimulating factor. Despite these promising results, responses have been uncommon in patients with visceral metastases. T-VEC is currently being evaluated in combination with other immune therapies (ipilimumab and pembrolizumab) with early signs of activity. In this review, we discuss the preclinical rationale, the clinical experience, and future directions for T-VEC in advanced melanoma.
Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. [2021]An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte-macrophage colony-stimulating factor (GMCSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.
Oncolytic Viruses for the Treatment of Metastatic Melanoma. [2021]There is an unmet need for additional treatments for metastatic melanoma, besides anti-PD1 antibodies which are FDA approved for adjuvant therapy for stage III or resected stage IV melanoma. Talimogene laherparepvec (T-VEC) is the first and only FDA-approved oncolytic virus for the treatment of melanoma. New viral vectors including coxsackieviruses, HF-10, adenovirus, reovirus, echovirus, and newcastle disease virus are currently under active development and investigation with varying degrees of efficacy in targeting melanoma. The use of T-VEC as a neoadjuvant therapy is emerging, but more data is needed at this point. T-VEC has also shown promise for use in combination therapy with ipilimumab, as T-VEC plus ipilimumab has a significantly higher objective response compared to ipilimumab alone. Data comparing T-VEC in combination with PD-1 checkpoint inhibitors is awaited, and a phase III trial is underway. It is likely that oncolytic viruses will have long-term application in the treatment of melanoma and that T-VEC in particular will continue to have a role in the treatment of patients with readily accessible cutaneous lesions both for local control and synergistic induction of antitumor immunity as part of combination therapies.
First oncolytic virus approved for melanoma immunotherapy. [2021]On 2015, October 27th, the US Food and Drug Administration (FDA) has officially approved talimogene laherparepvec (T-VEC, also known as OncoVEXGM-CSF) for use in melanoma patients with injectable but non-resectable lesions in the skin and lymph nodes. T-VEC (which is commercialized by Amgen, Inc. under the name of Imlygic®) becomes therefore the first oncolytic virus approved for cancer therapy in the US.
Local Delivery of OncoVEXmGM-CSF Generates Systemic Antitumor Immune Responses Enhanced by Cytotoxic T-Lymphocyte-Associated Protein Blockade. [2021]Purpose: Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus, we characterized local and systemic antitumor immune responses driving efficacy in murine syngeneic models.Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEXmGM-CSF (talimogene laherparepvec with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone or in combination with checkpoint blockade was characterized in A20 and CT-26 contralateral murine tumor models. CD8+ depletion, adoptive T-cell transfers, and Enzyme-Linked ImmunoSpot assays were used to study the mechanism of action (MOA) of systemic immune responses.Results: Treatment with OncoVEXmGM-CSF cured all injected A20 tumors and half of contralateral tumors. Viral presence was limited to injected tumors and was not responsible for systemic efficacy. A significant increase in T cells (CD3+/CD8+) was observed in injected and contralateral tumors at 168 hours. Ex vivo analyses showed these cytotoxic T lymphocytes were tumor-specific. Increased neutrophils, monocytes, and chemokines were observed in injected tumors only. Importantly, depletion of CD8+ T cells abolished all systemic efficacy and significantly decreased local efficacy. In addition, immune cell transfer from OncoVEXmGM-CSF-cured mice significantly protected from tumor challenge. Finally, combination of OncoVEXmGM-CSF and checkpoint blockade resulted in increased tumor-specific CD8+ anti-AH1 T cells and systemic efficacy.Conclusions: The data support a dual MOA for OncoVEXmGM-CSF that involves direct oncolysis of injected tumors and activation of a CD8+-dependent systemic response that clears injected and contralateral tumors when combined with checkpoint inhibition. Clin Cancer Res; 23(20); 6190-202. ©2017 AACR.
OncoVEXmGM-CSFexpands tumor antigen-specific CD8+ T-cell response in preclinical models. [2023]Label="BACKGROUND">Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) have demonstrated clinical efficacy in advanced melanoma, but only a subset of patients with inflamed tumors are responsive. Talimogene laherparepvec (T-VEC), a modified herpes simplex virus type 1 (HSV-1) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF), is a first-in-class oncolytic immunotherapy approved for the treatment of melanoma and has been shown to inflame the tumor microenvironment. To evaluate the potential and mechanisms of T-VEC to elicit systemic antitumor immunity and overcome resistance to checkpoint inhibitors in murine tumor models, OncoVEXmGM-CSF was developed similarly to T-VEC, except the human GM-CSF transgene was replaced with murine GM-CSF. Previous work had demonstrated that OncoVEXmGM-CSF generated systemic antitumor immunity dependent on CD8+ T cells in an immune checkpoint-sensitive tumor cell model.