Transmucosal Patch Yields Pathologic Responses in Non-Invasive Oral Cancer

PRV111, a nanoengineered, cisplatin-releasing transmucosal patch, achieved a 95.5% pathologic complete response (pCR) rate in patients with non-invasive oral cancer or high-grade dysplasia (HGD), eliminating the need for standard-of-care surgery in 100% of evaluable patients and demonstrating durable local control with no recurrences observed, according to a news release from the developer, Privo Technologies.¹ The run-in findings emerged from the phase 2/3 CLN-004 trial (NCT05893888).

What were the key efficacy results from the PRV111 phase 2 trial?

Among 22 evaluable patients enrolled in cohort 1 of the CLN-004 phase 2 study, 21 (95.5%) achieved a centrally confirmed pCR, defined as the absence of any residual dysplastic cells in post-treatment punch biopsy specimens as determined by histopathology. The remaining patient was downstaged from oral carcinoma in situ (CIS) to low-grade dysplasia, also avoiding the need for planned surgical excision. Treated mucosal surfaces healed completely with normal appearance and no scarring.

At a median follow-up of approximately 14 months (range, 8–21), no recurrences were observed in the treated areas. Several patients have maintained responses beyond 14 months, and the longest ongoing CR exceeds 21 months, according to the developers.

“The [pCR] rate of 95.5% and the treatment durability achieved with PRV111 is among the highest reported for localized therapies in this setting. Patients typically [have] repeated surgical resections, which can lead to scar formation, anatomic distortion, and functional impairments that can permanently affect speech and swallowing,” stated Eric Lamarre, MD, an investigator in the study and chief of head and neck surgical oncology at Cleveland Clinic, in the press release.¹ “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.”

What is the safety profile of PRV111?

PRV111 demonstrated a favorable tolerability profile. No systemic toxicities or dose-limiting toxicities (DLTs) were reported. Systemic cisplatin exposure remained negligible. Treatment-related adverse events (AEs) were predominantly mild, with 85% of events classified as grade 1, and none were serious. The most common treatment-related events were transient and primarily consisted of mild oral symptoms at the site of patch application. No clinically meaningful changes in standard laboratory parameters were observed.

What is the CLN-004 trial design?

CLN-004 is an open-label, multi-arm, phase 2/3 study evaluating PRV111 and PRV211, 2 nanoengineered cisplatin delivery systems, in patients with oral cavity cancers at distinct stages of disease.² The study is being conducted across 4 major US cancer centers specializing in head and neck oncology and is enrolling adults aged 18 years and older. Arm 1, which generated the current results, is evaluating PRV111 as a stand-alone, non-surgical topical therapy for patients with pathologically proven and clinically confirmed oral CIS (Tis) or HGD of the lip or oral cavity.

The primary objective of Arm 1 is to demonstrate safety and efficacy of PRV111, with the overall response rate (ORR) as the primary efficacy end point. Arm 2 of the study is separately evaluating PRV211, an intraoperative cisplatin delivery system, in patients with T1 to T3, Nx, M0 invasive oral cavity cancer who are candidates for surgery. With phase 2 data now complete, the developers are preparing to submit the CLN-004 dataset to the FDA to inform the design of a pivotal phase 3 trial.

What is PRV111 and how does it work?

PRV111 (Cisplatin Transmucosal System) is a thin, 2-layer, matrix-type polymeric patch that adheres directly to the oral lesion. Used in conjunction with a separately packaged permeation enhancer powder, the patch is designed to achieve rapid drug permeation of cisplatin into dysplastic epithelial tissue and adjacent regional lymphatics. By delivering high local concentrations of cisplatin directly into abnormal tissue, PRV111 aims to eliminate malignant and premalignant cells while maintaining negligible systemic drug exposure, avoiding the immunosuppression, nephrotoxicity, and other systemic harms associated with intravenous cisplatin administration.

The CLN-004 study builds on data from the earlier first-in-human phase 1/2 CLN-001 trial (NCT03502148), which showed promising local tumor responses with no systemic toxicity; those results were published in Nature Communications.³

What is the unmet need in oral carcinoma in situ and high-grade dysplasia?

Non-invasive oral cancer and HGD are common, frequently recurring conditions for which surgical excision remains the established standard of care. However, repeated surgical resection carries significant morbidity, including scar formation, anatomic distortion, and functional impairment affecting speech and swallowing. Recurrence rates after surgery remain high, requiring patients to undergo multiple procedures over their lifetimes.

Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent malignancies worldwide, and early-stage oral lesions, including CIS and HGD, represent critical intervention targets before invasive disease develops. No FDA-approved non-surgical therapy currently exists for this patient population, representing a meaningful unmet clinical need.

“[Privo Technologies] and the investigators in our CLN-004 study are excited by these encouraging results,” stated Manijeh Goldberg, PhD, MBA, chief executive officer, president, and founder of Privo Technologies, in the press release.¹ “We are one step closer to providing patients with a non-surgical alternative to repeated operative procedures.”

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 7, 2026. https://tinyurl.com/3yh927b3
2. A study evaluating the safety and efficacy of PRV111, PRV211, and PRV131 in subjects with oral and lung cancers. ClinicalTrials.gov. Updated April 20, 2026. Accessed October 7, 2026. https://tinyurl.com/495z2byn
3. Goldberg M, Manzi A, Birdi A, et al. A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. Nat Commun. 2022;13:4829. doi:10.1038/s41467-022-31859-3