PH-762 intratumoral pour le carcinome cutané
Étude sur l'augmentation de la dose du PH-762 intratumoral néoadjuvant pour le carcinome épidermoïde cutané, le mélanome ou le carcinome à cellules 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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Arizona
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Gilbert, Arizona, États-Unis, 85234
- Banner MD Anderson Cancer Center
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California
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San Diego, California, États-Unis, 92108
- Paradigm Clinical Research
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Florida
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Delray Beach, Florida, États-Unis, 33445
- Integrity Research
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Nevada
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Reno, Nevada, États-Unis, 89509
- Skin Cancer and Dermatology Institute
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Ohio
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Columbus, Ohio, États-Unis, 43213
- Centricity Research
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Adverse Events
Délai: 16 weeks
|
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events. |
16 weeks
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Pharmacokinetics: maximum plasma concentration (Cmax)
Délai: 3.5 weeks
|
Maximum concentration of PH-762 following intratumoral injection. |
3.5 weeks
|
|
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Délai: 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)
Délai: 3.5 weeks
|
Exposure to PH-762 through last quantifiable concentration following intratumoral injection. |
3.5 weeks
|
|
Pathologic response
Délai: 5 weeks
|
Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion. |
5 weeks
|
|
Tumor burden
Délai: 5 weeks
|
Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion. |
5 weeks
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Linda Mahoney, Phio Pharmaceuticals Inc.
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- PHIO-762-2301
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
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