PH-762 intratumoral para carcinoma cutâneo
Estudo de escalonamento de dose de PH-762 intratumoral neoadjuvante para carcinoma de células escamosas cutâneo, melanoma ou carcinoma de células de Merkel
The goal of this clinical trial is to evaluate the safety and tolerability of intratumoral injections of PH-762 in squamous cell carcinoma, melanoma, or Merkel cell carcinomas of the skin, to understand what the body does to the PH-762, and to observe how the tumor responds to the drug. Participants will receive four injections of PH-762 at weekly intervals, into a single tumor, followed by surgical removal of the tumor approximately two weeks later.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
PH-762 is a potent RNAi molecule targeting PD-1. PH-762 can inhibit the immune checkpoint PD-1 in the tumor and thereby impede tumor growth. As a preoperative therapy, it may decrease the lesion size and has the potential to improve surgical morbidity. Intratumoral immunotherapy aims to use the tumor as a 'self-vaccine'. The local immune stimulation can induce robust priming of an anti-tumor immune response while generating systemic (abscopal) tumor responses, mediated by properly activated anti-tumor immune cells in the circulation. Local delivery of immunotherapy is expected to minimize systemic exposure and off-target toxicities.
This is a non-comparative study of neoadjuvant monotherapy using PD-1 targeting self-delivering RNAi (PH-762) in adult subjects with cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma. The study treatment consists of four intratumoral injections of PH-762 at weekly intervals, into a single tumor lesion. Excision of the tumor will occur approximately two weeks following the fourth dose of IT PH-762, and the subjects will be followed for an additional 11 weeks.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Arizona
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Gilbert, Arizona, Estados Unidos, 85234
- Banner MD Anderson Cancer Center
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California
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San Diego, California, Estados Unidos, 92108
- Paradigm Clinical Research
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Florida
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Delray Beach, Florida, Estados Unidos, 33445
- Integrity Research
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Nevada
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Reno, Nevada, Estados Unidos, 89509
- Skin Cancer and Dermatology Institute
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Ohio
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Columbus, Ohio, Estados Unidos, 43213
- Centricity Research
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Key Inclusion Criteria:
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Histologically confirmed cutaneous squamous cell carcinoma (cSCC), melanoma, or Merkel cell carcinoma, meeting one of the following criteria:
- cSCC, resectable local tumors: must be Stage II or lower, amenable to curative resection and in a location where acceptable surgical margins are anticipated
- cSCC, unresectable local tumors: must be Stage II or lower, tumor has been unresponsive to prior radiation therapy or is not a candidate for curative radiation therapy
- cSCC, metastatic disease: disease has progressed during or following prior checkpoint inhibitor therapy (anti-PD-1 or anti-PD-L1 antibody)
- Melanoma, metastatic disease: Stage IV disease with a cutaneous lesion that has progressed during or following checkpoint inhibitor therapy (anti-PD-1/-PD-L1), and if BRAF-mutation is present, has progressed during or following prior treatment with anti-BRAF + MEK therapy
- Merkel cell carcinoma, metastatic disease: Stage IV disease with a cutaneous lesion that has progressed during or following checkpoint inhibitor therapy (anti-PD-1/PD-L1)
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A minimum of one tumor of ≥ 1.0 cm and < 3.0 cm in longest dimension that is accessible (with or without imaging guidance) for intratumoral injection and for biopsy and surgical excision must be present. The tumor is not necrotic, hemorrhagic, or friable, and is not within 2 cm of the eye or within 0.5 cm of or on the lip (including the vermilion border) and is not in a mucosal or visceral location.
Key Exclusion Criteria:
- Other malignancy within prior 3 years, with certain exceptions.
- Current cancer chemotherapy, radiation therapy, immunotherapy, or biologic therapy.
- Any serious or uncontrolled medical disorder including auto-immune disease that may increase the risk associated with study participation or study drug administration, or interfere with the interpretation of study results.
- Females who are pregnant or are breastfeeding.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Sequential escalating doses of PH-762.
Escalating doses of PH-762 are to be tested, with an observation period between doses. |
PH-762 is a potent RNAi molecule targeting PD-1. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Adverse Events
Prazo: 16 weeks
|
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events. |
16 weeks
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Pharmacokinetics: maximum plasma concentration (Cmax)
Prazo: 3.5 weeks
|
Maximum concentration of PH-762 following intratumoral injection. |
3.5 weeks
|
|
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Prazo: 3.5 weeks
|
Time to maximum concentration of PH-762 following intratumoral injection. |
3.5 weeks
|
|
Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
Prazo: 3.5 weeks
|
Exposure to PH-762 through last quantifiable concentration following intratumoral injection. |
3.5 weeks
|
|
Pathologic response
Prazo: 5 weeks
|
Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion. |
5 weeks
|
|
Tumor burden
Prazo: 5 weeks
|
Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion. |
5 weeks
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Diretor de estudo: Linda Mahoney, Phio Pharmaceuticals Inc.
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- PHIO-762-2301
Plano para dados de participantes individuais (IPD)
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