Squamous Cell Carcinoma of the SkinPhase 1NCT06014086
Intratumoral PH-762 for Cutaneous Carcinoma
A Phase 1 study testing PH-762 in people with Squamous Cell Carcinoma of the Skin and Malignant Melanoma of Skin, run by Phio Pharmaceuticals Inc. at 5 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Skin, Malignant Melanoma of Skin, Merkel Cell Carcinoma of Skin
- What is being tested?
- PH-762
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesUnited States
- Study dates
- 7 Nov 2023to 17 Mar 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Centricity Research
Columbus, Ohio, 43213
Integrity Research
Delray Beach, Florida, 33445
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Skin Cancer and Dermatology Institute
Reno, Nevada, 89509
Paradigm Clinical Research
San Diego, California, 92108
About this study
Official title: Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma
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.
Read the detailed description
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.
- Conditions
- Squamous Cell Carcinoma of the Skin, Malignant Melanoma of Skin, Merkel Cell Carcinoma of Skin
- Being tested
- PH-762
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PH-762Drug
PH-762 is a potent RNAi molecule targeting PD-1.
| Study group | Role | What they receive |
|---|---|---|
| Sequential escalating doses of PH-762. | Experimental | Escalating doses of PH-762 are to be tested, with an observation period between doses. Receives: Drug: PH-762 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events.
Measured: 16 weeks
Secondary outcomes (5)
Pharmacokinetics: maximum plasma concentration (Cmax)
Maximum concentration of PH-762 following intratumoral injection.
Measured: 3.5 weeks
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Time to maximum concentration of PH-762 following intratumoral injection.
Measured: 3.5 weeks
Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
Exposure to PH-762 through last quantifiable concentration following intratumoral injection.
Measured: 3.5 weeks
Pathologic response
Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion.
Measured: 5 weeks
Tumor burden
Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2023
- Study start7 Nov 2023
- Primary completion29 Dec 2025
- Study completion17 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of the SkinStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phio Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Prosoft Clinical
- Responsible party
- Sponsor
- Investigators
- Linda Mahoney, Study director, Phio Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06014086
- Sponsor's protocol ID
- PHIO-762-2301
- Status last verified
- Sep 2026
- First submitted
- 22 Aug 2023
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cuiffo B, Maxwell M, Yan D, Guemiri R, Boone A, Bellet D, Rivest B, Cardia J, Robert C, Fricker SP. Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy. Front Immunol. 2024 Dec 4;15:1501679. doi: 10.3389/fimmu.2024.1501679. eCollection 2024.
PubMed 39697325
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06014086
- Acronym / sponsor ID
- PHIO-762-2301
- Conditions
- Squamous Cell Carcinoma of the Skin, Malignant Melanoma of Skin, Merkel Cell Carcinoma of Skin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Phio Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- Prosoft Clinical
- Study start
- 7 Nov 2023 (actual)
- Primary completion
- 29 Dec 2025 (actual)
- Study completion
- 17 Mar 2026 (actual)
- First posted
- 28 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sequential escalating doses of PH-762. | Experimental | Drug: PH-762Escalating doses of PH-762 are to be tested, with an observation period between doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically confirmed cutaneous squamous cell carcinoma (cSCC), melanoma, or Merkel cell carcinoma, meeting one of the following criteria:
- 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 (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PH-762PH-762 is a potent RNAi molecule targeting PD-1. | Drug | Sequential escalating doses of PH-762. |
Primary outcome
Adverse Events
Time frame: 16 weeks
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events.
5 secondary outcomes
Pharmacokinetics: maximum plasma concentration (Cmax)
Time frame: 3.5 weeks
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Time frame: 3.5 weeks
Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
Time frame: 3.5 weeks
Pathologic response
Time frame: 5 weeks
Tumor burden
Time frame: 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 39697325Cuiffo B, Maxwell M, Yan D, Guemiri R, Boone A, Bellet D, Rivest B, Cardia J, Robert C, Fricker SP. Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy. Front Immunol. 2024 Dec 4;15:1501679. doi: 10.3389/fimmu.2024.1501679. eCollection 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda Mahoney study director
Phio Pharmaceuticals Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PH-762 in people with Squamous Cell Carcinoma of the Skin and Malignant Melanoma of Skin, run by Phio Pharmaceuticals Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06014086, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.