Cisplatin-Releasing PRV111 Patch Elicits High pCR Rate in Early-Stage Oral Cancer

A single cycle of PRV111, a nanoengineered, cisplatin-releasing topical patch, drove centrally confirmed pathologic complete responses (pCRs) in patients with noninvasive oral cancer or high-grade dysplasia, according to updated data from cohort 1 of the phase 2 portion of the ongoing CLN-004 trial (NCT05893888).¹

Findings showed that evaluable patients (n = 22) achieved a pCR rate of 95.5%, and the lone patient who did not experience pCR was downstaged from oral carcinoma in situ (CIS) to low-grade dysplasia. All patients avoided their planned standard-of-care surgery, and treated mucosa healed completely, with a normal appearance and no scarring.

At a median follow-up of 14 months (range, 8-21), no recurrences had been observed, and the longest ongoing response exceeded 21 months.

"The [pCR] rate of 95.5% and the treatment durability achieved with PRV111 is among the highest reported for localized therapies in this setting," Eric Lamarre, MD, chief of head and neck surgical oncology at Cleveland Clinic in Ohio and a study investigator, stated in a news release. "Patients typically face repeated surgical resections, which can lead to scar formation, anatomic distortion, and functional impairments that can permanently affect speech and swallowing. This non-surgical patch not only cleared the disease but preserved native tissue function without causing significant scar formation. These results reinforce PRV111's potential to redefine the standard of care for oral carcinoma in situ and dysplasias. We are one step closer to providing patients with a non-surgical alternative to repeated operative procedures."

Systemic cisplatin exposure was negligible, and no systemic toxicities or dose-limiting toxicities (DLTs) were reported. Of the treatment-related adverse effects (AEs) observed, 85% were mild, and no serious AEs occurred; treatment-related AEs were primarily mild, transient oral symptoms.

The study is still recruiting and has an estimated primary completion date of October 2026.²

What is the CLN-004 trial design?

The multicenter phase 2/3 CLN-004 trial is evaluating 3 localized cisplatin formulations from Privo's PRV platform (PRV111, PRV211, and PRV131) in patients with oral cavity cancer and, in 1 arm, lung cancer, with a planned enrollment of 40 patients across arms.

Arm 1 is evaluating PRV111 in patients with pathologically proven and clinically confirmed CIS (Tis) of the lip or oral cavity; arm 2 is evaluating PRV211, an intraoperative formulation placed in the resected tumor bed, in patients with T1 to T3 disease; and arm 3 is evaluating PRV131, an intratumoral injectable formulation. Participating sites include City of Hope National Medical Center, Miami Cancer Institute, the University of Chicago, and Cleveland Clinic.

To be eligible for arm 1, patients needed to be at least 18 years of age and have lesions with histopathologic changes warranting surgical intervention; an accessible tumor with no evidence of infection or active bleeding; a tumor amenable to surgical resection within 8 weeks of screening; clinically and/or radiologically measurable disease; an ECOG performance status of 2 or lower; and a life expectancy of at least 3 months.

Key arm 1 exclusion criteria included a prior history of invasive squamous cell carcinoma (SCC), tumors involving the marginal gingiva, previous radiotherapy for SCC of the oral cavity, systemic chemotherapy for head and neck SCC within 2 years of screening, oral submucous fibrosis, and trismus.

PRV111 is a self-adhesive, 2-layer transmucosal patch consisting of a chitosan matrix embedded with cisplatin-loaded chitosan particles; a reconstituted permeation enhancer solution is applied before the patch is placed over the lesion. The protocol specifies a cisplatin dose of 1.5 mg/cm² per visit, and patients must complete at least 3 treatment visits to be evaluable for efficacy. Patients whose disease does not improve compared with their baseline biopsy proceed to scheduled surgery.

In cohort 1, response was confirmed by post-treatment punch biopsy and histopathology.¹

The primary end point for arm 1 is overall response rate, defined as histopathologic downgrading of disease (partial or complete response) on post-treatment biopsy compared with baseline and/or a clinically measurable tumor volume reduction of at least 30%.² Secondary end points include event-free survival, with events defined as salvage surgery, locoregional recurrence at 12 months, or death from any cause, and pharmacokinetic assessment of platinum levels in blood.

What data were previously reported for the PRV platform?

The CLN-004 study builds on the first-in-human phase 1/2 CLN-001 study (NCT03502148), which showed local tumor responses with no systemic toxicity; those findings were published in Nature Communications.¹

In arm 2 of CLN-004, PRV211 was associated with no treatment-related serious AEs, systemic toxicities, or DLTs in a phase 1/2 safety cohort (n = 8) of patients with invasive oral cavity cancer.³

References

1. Clinical update from the ongoing phase 2 trial of PRV111, the first non-surgical therapy in development for early-stage oral cancer. News release. Privo Technologies. October 5, 2026. Accessed October 5, 2026. https://www.prnewswire.com/news-releases/clinical-update-from-the-ongoing-phase-2-trial-of-prv111-the-first-non-surgical-therapy-in-development-for-early-stage-oral-cancer-302897995.html
2. A phase 1/2/3 multicenter study evaluating the PRV platform of localized nanoengineered therapies for oral cavity and lung cancers. ClinicalTrials.gov. Accessed October 5, 2026. https://clinicaltrials.gov/study/NCT05893888
3. PRV211 Generates Promising Safety Outcomes in Invasive Oral Cavity Cancer. OncLive. Published February 2, 2026. Accessed October 5, 2026. https://www.onclive.com/view/prv211-generates-promising-safety-outcomes-in-invasive-oral-cavity-cancer