RP1 for Skin Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Sherrif Ibrahim
Must not be taking: Antivirals, Immunosuppressants, Antibiotics, others
Disqualifiers: Visceral metastases, Autoimmune disease, Cardiovascular disease, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a Phase 1b, single-center, open-label study, evaluating efficacy and safety of RP1 for the treatment of resectable cutaneous Squamous Cell Carcinoma in up to 12 evaluable patients. In this study, patients will receive RP1 via direct intratumoral (IT) injection into superficial cutaneous solid tumors to assess the safety and tolerability as well efficacy of RP1 treatment. The primary efficacy population is up to 12 evaluable patients with resectable CSCC. The enrollment of patients with CSCC will determine study duration.
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 use antiviral medications with antiherpetic activity or botanical preparations during the study.
What data supports the effectiveness of the treatment RP1, vusolimogene oderparepvec, for skin cancer?
Research on a similar treatment, talimogene laherparepvec (T-VEC), shows it can help treat advanced melanoma by directly killing cancer cells and boosting the immune system's response. T-VEC has been approved by the FDA for treating melanoma that cannot be surgically removed, suggesting potential effectiveness for similar treatments like RP1.
12345How is the treatment RP1 (vusolimogene oderparepvec) for skin cancer different from other treatments?
RP1 (vusolimogene oderparepvec) is an oncolytic viral therapy, similar to talimogene laherparepvec (T-VEC), which works by directly destroying cancer cells and stimulating the immune system to attack tumors. This approach is unique compared to traditional treatments like chemotherapy or radiation, as it uses a virus to target cancer cells specifically.
34678Eligibility Criteria
This trial is for adults over 18 with resectable cutaneous Squamous Cell Carcinoma who haven't had treatment on the target lesion. They should be in good health, have a life expectancy over 2 years, and tumors between 1.0 and 3.0 cm in size that are visible and can be measured.Inclusion Criteria
My targeted cancer area has not received any treatment.
I am 18 years old or older.
My blood clotting levels are within a normal range.
+8 more
Exclusion Criteria
My tumor's edges are not clearly defined.
Documented history of allergic reactions or acute hypersensitivity reaction attributed to RP1 or to any of the excipients
Patients with a history of any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating the presence of the virus, or human immunodeficiency virus (HIV) positive
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive RP1 via direct intratumoral injection into superficial cutaneous solid tumors to assess safety, tolerability, and efficacy
16 weeks
Multiple visits for intratumoral injections
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Long-term follow-up
Participants are monitored for progression-free survival and other secondary outcomes
2 years
Participant Groups
The study tests RP1, an investigational drug given by direct injection into the tumor of patients with Squamous Cell Carcinoma. It aims to evaluate its safety, tolerability, and effectiveness in up to 12 participants.
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment1 Intervention
Patients will receive RP1 via direct intratumoral (IT) injection into superficial cutaneous solid tumors to assess the safety and tolerability as well efficacy of RP1 treatment. The primary efficacy population is up to 12 evaluable patients with resectable CSCC.
RP1 is already approved in United States for the following indications:
🇺🇸 Approved in United States as vusolimogene oderparepvec for:
- Advanced melanoma in patients who have previously received an anti-PD1 containing regimen
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rochester Dermatologic SurgeryVictor, NY
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Who Is Running the Clinical Trial?
Sherrif IbrahimLead Sponsor
References
Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2). [2022]Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.
Triple threat to cancer: rationale for combining oncolytic viruses, MEK inhibitors, and immune checkpoint blockade. [2021]In a recent edition of Science Translational Medicine, we identified an enhanced therapeutic activity when talimogene laherparepvec (T-VEC) was combined with MEK inhibition in murine melanoma tumor models. MEK inhibition increased viral replication independent of mutation status. Combination therapy increased PD-1/PD-L1 expression and PD-1 blockade further enhanced tumor regression. Further clinical development of this strategy for treating melanomas warranted.
Talimogene Laherparepvec for the Treatment of Advanced Melanoma. [2021]Talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus that mediates local and systemic antitumor activity by direct cancer cell lysis and an "in situ vaccine" effect. Based on an increased durable response rate compared with granulocyte macrophage-colony stimulating factor in a randomized phase III trial, it was approved by the FDA for the treatment of melanoma metastatic to skin or lymph nodes. The drug is currently in clinical trials as monotherapy and in combination with immune-checkpoint inhibitors and radiotherapy in melanoma and other cancers. The mechanism of action, toxicity, and efficacy as well as its role in current clinical practice and potential future applications are reviewed. Clin Cancer Res; 22(13); 3127-31. ©2016 AACR.
First Oncolytic Viral Therapy for Melanoma. [2017]The FDA has approved talimogene laherparepvec, or T-VEC, to treat surgically unresectable skin and lymph node lesions in patients with advanced melanoma. T-VEC is the first oncolytic viral therapy to gain regulatory endorsement, based on data from the OPTiM study.
MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation. [2021]Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in delayed tumor growth and improved survival in mouse models. Tumor regression was dependent on activated CD8+ T cells and Batf3+ dendritic cells. We also observed antigen spreading and induction of an inflammatory gene signature, including increased expression of PD-L1. Triple therapy with the combination of T-VEC, MEK inhibition, and anti-PD-1 antibody further augmented responses. These data support clinical development of combination oncolytic viruses, MEK inhibitors, and checkpoint blockade in patients with melanoma.
Clinical Challenges with Talimogene Laherparepvec: Cured Lymph Nodes Masquerading as Active Melanoma. [2020]Talimogene laherparepvec is a novel, genetically engineered, oncolytic herpes virus approved for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. It is administered as an intralesional injection. However, if the lesion continues to persist, it presents with a clinical challenge as when to stop treatment. Herein, we present two cases from our institution wherein the disease appeared to be persistent radiologically; however, on pathological excision, there was no evidence of disease and patients continue to be in durable remission after stopping treatment.
Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. [2021]Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB-IV melanoma.
Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas. [2023]Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.