Phase 1b trial — intratumoral siRNA cancer drug PH-762 in cutaneous carcinoma (NCT06014086), late-breaking session at AAD 2026 · phase 2b planned for Q1 2027
In a phase 1b trial of the siRNA cancer drug PH-762, injected directly into cutaneous squamous cell carcinoma, 13 of 20 patients (65%) had a pathologic response and 9 (45%) had no cancer cells left in the tumor removed at surgery. In the highest-dose cohort, 6 of 7 patients (85%) responded. No dose-limiting toxicities or serious adverse events were reported at any dose, and the developer is preparing a phase 2b trial for the first quarter of 2027.
How does an siRNA cancer drug work?
siRNA (small interfering RNA) is a short piece of RNA about 20 bases long. Inside a cell it finds the messenger RNA of one specific gene and cuts it, so the protein is never made. This process is called RNA interference. Because it acts on genetic instructions rather than on proteins, siRNA belongs to the nucleic acid medicine family. Since the US FDA approved the first siRNA drug, patisiran for a rare inherited nerve disease, in August 2018, several siRNA medicines have entered patient care.
PH-762 is an siRNA cancer drug developed by the US company Phio Pharmaceuticals. It targets PDCD1, the gene that makes PD-1, a brake on immune cells. Tumors use this brake to escape immune attack. PH-762 lowers PD-1 in immune cells around the tumor so they can attack the cancer again. The goal is the same as intravenous PD-1 immunotherapy, but the drug is placed only in the tumor to limit exposure to the rest of the body.
The drug uses the company's self-delivering INTASYL design. Most siRNA needs a carrier such as a lipid nanoparticle to enter cells; PH-762 is chemically modified to enter cells without one. See our nucleic acid medicine and aptamer guide and cancer gene therapy overview for background.
Which skin cancer patients were included?
Cutaneous squamous cell carcinoma (cSCC) arises from cells in the outer layer of the skin and is the second most common skin cancer after basal cell carcinoma. It often appears on sun-exposed areas such as the face, ears and backs of the hands, and most cases are treated with surgery. When a tumor is large or sits where scarring and function matter, as on the face, surgery can be extensive, so treatments that shrink the tumor before surgery are drawing interest.
The phase 1b trial accepted patients with stage 1, 2 or 4 cSCC, stage 4 melanoma and stage 4 Merkel cell carcinoma. In total, 22 patients completed treatment and tumor removal, 20 of them with cSCC. For another local treatment in skin cancer, see the melanoma oncolytic virus Tudriqev.
How is PH-762 given?
The drug is given before surgery (neoadjuvant treatment) on this schedule:
- Injections: PH-762 injected into the tumor once a week, four times
- Dose: five cohorts with stepwise escalation; the last cohort received a 20-fold higher concentration than the first
- Surgery and assessment: the tumor was removed about two weeks after the last injection and examined under the microscope for remaining cancer cells (pathologic response)
Phase 1b results: 65% response in cutaneous squamous cell carcinoma
Mary C. Spellman, MD, presented the results in a late-breaking research session at the American Academy of Dermatology annual meeting in Denver in March 2026. A response meant that more than half of the cancer cells had cleared in the removed tissue. After its first announcement in January, the company reviewed the data and issued revised figures on February 10; the table uses the revised figures.
| 20 patients with cSCC | Patients |
|---|---|
| Complete response (100% clearance) | 9 (45%) |
| Major response (over 90% clearance) | 2 |
| Partial response (over 50% clearance) | 2 |
| Overall response | 13 (65%) |
| Highest-dose cohort | 6 of 7 (85%); 4 of the 6 responders had a complete response |
Sources: Phio Pharmaceuticals announcement (2026-02-10, revised data) and Dermatology Times AAD 2026 report. Pathologic response is based on microscopic review of the surgically removed tumor.
The one patient with metastatic Merkel cell carcinoma also had a partial response, and no patient's disease progressed during the study. Because the highest dose gave the best results, the company plans to carry this dose into the next trial.
Dr. Spellman noted that inflammation or scarring after injections can confound measurements of tumor size, so pathologic response is a more reliable measure of effect. A phase 1b trial is designed to find a safe dose in a small group, and larger trials will now look at how well and how long the treatment works.
What side effects were reported?
No dose-limiting toxicities or serious adverse events were reported in any of the 22 patients. The meeting presentation also reported no immune-related adverse events, which the investigators linked to the drug staying mainly around the injected tumor. If redness or swelling at the injection site is bothersome, tell your care team so they can help manage it.
Development stage and where it is available
PH-762 is an investigational drug. The phase 1b trial finished in June 2026, and the company submitted its final study report to the US FDA with a request for a meeting on the next trial design. According to the company's November 5, 2026 update, the FDA response is expected by the end of November, and a phase 2b trial in patients with cSCC before surgery is planned to start in the first quarter of 2027.
As of November 2026 no country, including Japan, has approved the drug, so access is through clinical trials. Eligibility and sites for new trials will be listed on ClinicalTrials.gov; the phase 1b trial is NCT06014086. For human results with other nucleic acid cancer drugs, see aptamer cancer drug clinical results.
What to check and questions for your doctor
- What stage is my cSCC, and would shrinking the tumor before surgery help in my case?
- Which treatments are available now to reduce the extent of surgery?
- Is there an siRNA cancer drug trial, such as the PH-762 phase 2b, that I could join?
- How would injections into the tumor change my surgery schedule?
Frequently asked questions
How is an siRNA cancer drug different from other cancer drugs?
Most drugs bind to proteins that already exist. siRNA cuts the messenger RNA that carries the instructions, so the protein is not made. PH-762 uses this approach to reduce the PD-1 brake on immune cells.
What is the response rate of PH-762?
In the phase 1b trial, 13 of 20 patients with cSCC (65%) responded and 9 (45%) had a complete response. In the highest-dose cohort, 6 of 7 (85%) responded.
How many PH-762 injections are given?
In the phase 1b trial, the drug was injected into the tumor once a week for four weeks, and the tumor was removed about two weeks after the last injection.
When will PH-762 be available?
It is not yet approved. Patients can receive it through clinical trials, including the phase 2b trial planned for the first quarter of 2027. Approval timing will depend on later trial results and regulatory review.
Sources
- Phio Pharmaceuticals — Safety Monitoring Committee's positive wrap-up on PH-762 in skin cancer trial (revised response data, 2026-02-10)
newsfilecorp.com
Checked: 2026-11-12 - Dermatology Times — AAD 2026: Intratumoral PH762 shows early efficacy in cutaneous SCC with no immune-related adverse events
dermatologytimes.com
Checked: 2026-11-12 - Phio Pharmaceuticals — Key tumor response data from all cohorts in intratumoral PH-762 dose escalation trial (study design, 2026-01-20)
newsfilecorp.com
Checked: 2026-11-12 - Phio Pharmaceuticals — Third quarter 2026 financial results and business update: PH-762 toward phase 2b (2026-11-05)
finviz.com
Checked: 2026-11-12 - ClinicalTrials.gov — NCT06014086, intratumoral PH-762 in cutaneous carcinoma
clinicaltrials.gov
Checked: 2026-11-12 - PharmTech — FDA approves first-of-its-kind RNA therapy (patisiran, 2018)
pharmtech.com
Checked: 2026-11-12
Written by the FTH editorial team, sources checked 2026-11-12 · Medical review: none
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your care team.
