PH-762 intratumorale per carcinoma cutaneo
Studio di incremento della dose del PH-762 intratumorale neoadiuvante per il carcinoma cutaneo a cellule squamose, melanoma o carcinoma a cellule di 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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Arizona
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Gilbert, Arizona, Stati Uniti, 85234
- Banner MD Anderson Cancer Center
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California
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San Diego, California, Stati Uniti, 92108
- Paradigm Clinical Research
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Florida
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Delray Beach, Florida, Stati Uniti, 33445
- Integrity Research
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Nevada
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Reno, Nevada, Stati Uniti, 89509
- Skin Cancer and Dermatology Institute
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Ohio
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Columbus, Ohio, Stati Uniti, 43213
- Centricity Research
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Adverse Events
Lasso di tempo: 16 weeks
|
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events. |
16 weeks
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Pharmacokinetics: maximum plasma concentration (Cmax)
Lasso di tempo: 3.5 weeks
|
Maximum concentration of PH-762 following intratumoral injection. |
3.5 weeks
|
|
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Lasso di tempo: 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)
Lasso di tempo: 3.5 weeks
|
Exposure to PH-762 through last quantifiable concentration following intratumoral injection. |
3.5 weeks
|
|
Pathologic response
Lasso di tempo: 5 weeks
|
Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion. |
5 weeks
|
|
Tumor burden
Lasso di tempo: 5 weeks
|
Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion. |
5 weeks
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Direttore dello studio: Linda Mahoney, Phio Pharmaceuticals Inc.
Pubblicazioni e link utili
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Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- PHIO-762-2301
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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