A Phase 1/2/3 Multicenter Study Evaluating the PRV Platform of Localized Nanoengineered Therapies for Oral Cavity and Lung Cancers

Summary

Arm 1 ( Phase 2/3 Run in ): PRV111: Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017) Arm 2 (Phase 1) PRV211: Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting Arm 3 (Phase 1/2) PRV131: Intratumoral Injectable delivery into the Tumor Primary Endpoint: Safety and Objective Response Rate (ORR) Primary objective: Determine a safe and effective dose for PRV131 intratumoral injectable Subject Assignment: Subjects will be assigned to Arm 1, Arm 2, or Arm 3 of this study based on disease staging Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity Arm 3a: Histologically confirmed squamous cell carcinoma (SCC) of the oral cavity, classified as clinical stage T1-T3, N0-1, M0 Arm 3b: Histologically confirmed malignant tumor in the lungs (primary or secondary), classified as clinical stage T1-2, N0, M0

Detailed description

Privo's PRV111 \& PRV211 \& PRV131 Product Description: PRV111 (Cisplatin Transmucosal System) is a thin, 2-layer, matrix-type, transmucosal patch consisting of a chitosan matrix layer embedded with cisplatin loaded chitosan particles (CLPs) and a non-woven fabric adhesive unidirectional backing, which is applied to the matrix layer during manufacturing. The patch is self-adhesive. In addition to the PRV111 patch, a separately packaged Permeation Enhancer (PE) Powder for Reconstitution is used in conjunction with PRV111. The reconstituted PE Solution is intended to improve the absorption of the cisplatin active ingredient and will be applied prior to patch application. PRV211 is a nanoengineered delivery system intended for intraoperative chemotherapy treatment for all solid tumor surgeries immediately following surgical excision. The goal is to treat the tumor bed locally, eliminating any remaining micrometastases or close margins that are unable to be fully resected while avoiding system circulation. PRV131 is a nanoparticle-based cisplatin formulation designed for intratumoral administration. The product is reconstituted with a separately packaged diluent to form a suspension for injection. Upon intratumoral administration, the nanoparticles facilitate deep tumor penetration and localized drug release, enabling high local drug concentrations while minimizing systemic exposure. ARM 1 Study Details PRV111 Topical Treatment Screening: A screening period of up to 7 days is needed to evaluate subject eligibility for study participation. All subjects will undergo a baseline histopathological assessment at screening (confirming CIS of the oral cavity for inclusion), if an existing diagnosis does not exist. Also at screening, the investigator will determine if the patient requires surgery, and will assess the rest of the inclusion/exclusion criteria to check for eligibility. Dose limiting Toxicity (DLT): DLT is defined as a clinically significant treatment-emergent AE (TEAE) or laboratory abnormality unrelated to surgery and/or disease progression, concurrent illness, or concomitant therapy within 1-month post-surgery Note: The dosing of 1.5 mg/cm2 per visit in this protocol is comparable to the one used in the prior completed phase 1/2 CLN-001 study, which has shown safety and efficacy causing no dose limiting toxicities (DLTs), related severe adverse events (SAEs) or systemic side effects. Photo documentation: Tumors will be photographed including anatomic landmarks at each visit, prior to treatment at treatment visits for the ability to compare between visits. Photos are also required for documenting the location of biopsies taken. Additional details are provided in the Lab Manual. Minimum Required Treatments for Efficacy Assessment: For assessing efficacy, each subject must complete at least 3 treatment visits. Assessment for Postponement of Surgery: Response Assessment Criteria: If disease is not improved compared to baseline biopsy, subject proceeds to scheduled surgery, otherwise the subject will continue on with the PRV111 treatment regimen. ARM 2 Study Details PRV211 Intraoperative Treatment Screening: A screening period of up to 7 days is needed to evaluate subject eligibility for study participation. All subjects will be screened based on the SOC biopsy to obtain baseline histopathology. This biopsy will confirm the stage of the disease to be T1-T3, Nx, M0 of the oral cavity, amenable to surgery. Based on this confirmation, the rest of the inclusion/exclusion criteria will be checked for eligibility. Safety and Efficacy of PRV211 Treatment: The safety of PRV211 treatment will be determined in the Safety Run-in study described below. Once the safety is determined, a second expansion study can be initiated in another study. The efficacy of PRV211 is determined in the expansion study. This efficacy will be assessed by the incidence of locoregional recurrence at 12 months. Initial Safety Lead-in Study: This is an open label, safety lead-in phase 1b dose confirmation study in patients with T1-T3, Nx, M0 oral cancer, followed by an expansion phase 2 single arm study as an intraoperative chemotherapy with PRV211. For the purpose of safety detection, if greater than 33% of subjects being evaluated for safety present with dose-limiting toxicities (DLTs), the study is deemed unsafe. For the Safety Lead-in Study, 3 subjects will be initially enrolled. If more than 1 subject has dose limiting toxicity (DLT), the study stops. Otherwise, 3 additional subjects will be enrolled and if more than 2 DLTs are detected in the total of 6 subjects, the study is deemed unsafe and the study stops. If 2 or less DLTs are observed, the treatment will be considered safe. At the conclusion of the Safety Lead-in portion (6 patients), if PRV211 is determined to be safe, an expansion study can be initiated. The 6 subjects from the Safety Lead-in study will be included in the expansion study and these patients will be monitored for efficacy. ARM 3 Study Details PRV131 Intratumoral Injectable Screening: A screening period of up to 7 days is needed to evaluate subject eligibility for study participation. All subjects will undergo baseline histopathological confirmation prior to enrollment. For subjects assigned to Arm 3a, disease must be confirmed as squamous cell carcinoma (SCC) of the oral cavity, classified as T1-T3, N0-1, M0. For subjects assigned to Arm 3b, disease must be confirmed as a malignant tumor in the lungs (primary or secondary), classified as T1-T2, N0, M0. Baseline imaging and clinical assessments will be performed per standard of care (SOC) to confirm tumor accessibility for intratumoral injection and surgical eligibility. Safety and Efficacy of PRV131 Treatment: The safety and preliminary efficacy of PRV131 will be evaluated in a Phase 1/2 run-in study designed to determine a safe and effective dose for intratumoral administration. Safety will be assessed based on the incidence of dose-limiting toxicities (DLTs), adverse events, and clinical laboratory findings. Efficacy will be evaluated based on Objective Response Rate (ORR), as determined by clinical, radiologic, and histopathological assessment of tumor response following treatment. Dose Escalation and Optimization: This is an open-label, dose escalation and dose optimization study utilizing a standard 3+3 design. Three subjects will initially be enrolled in the medium dose cohort. If no DLTs are observed, dose escalation will proceed. If one DLT is observed, the cohort will be expanded to 6 subjects. If two or more DLTs are observed at any dose level, escalation will be halted and the prior dose level may be considered the maximum tolerated dose (MTD). If one or fewer DLTs are observed among 6 subjects, escalation may continue. Following dose escalation, additional subjects may be enrolled in a dose optimization phase to further evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy. Treatment Administration: Treatment is customized based on tumor size and delivered directly into the tumor to maximize local drug concentration while minimizing systemic exposure. Subjects in Arm 3a will receive 2 to 3 intratumoral injections approximately 1 to 2 weeks apart prior to surgical resection. Subjects in Arm 3b will receive a single intratumoral injection, which may be administered during diagnostic bronchoscopy or at a subsequent visit following confirmation of malignancy. Surgical resection will occur approximately 2 to 4 weeks following treatment. Post-Treatment and Surgical Assessment: All subjects will proceed to standard-of-care surgical resection following PRV131 treatment. Resected tumor tissue will undergo histopathological evaluation to assess treatment response. Imaging and clinical findings will be compared with histopathological outcomes to evaluate the consistency and predictability of treatment effect. Subjects will be followed per SOC to monitor safety, recurrence, and durability of response.

Arms & interventions

• DrugPRV211 (Intraoperative Cisplatin System)

  PRV211 system is comprised of two parts, a liquid permeation enhancer (PE) and cisplatin patch. The permeation is brushed onto the resected tumor bed and after 5 minutes the patch can be applied directly over the same area. Apply up to 2 layers of the PRV211 system to the tumor bed post-resection. The duration of the PRV211 treatment takes approximately 10-20 minutes and then the surgeon can continue as planned with the rest of the standard of care procedure. The proposed starting dose is 0.5 mg/cm2 of cisplatin on the tumor bed. This approach can be safe and effective in preventing locoregional recurrence after surgery and eliminating high-risk factors for local recurrence, such as dysplasia at the margins.

• DrugPRV111 (Cisplatin Transmucosal System)

  PRV111 (Cisplatin Transmucosal System) is a thin, 2-layer, matrix-type, transmucosal patch consisting of a chitosan matrix layer embedded with cisplatin loaded chitosan particles (CLPs) and a non-woven fabric adhesive unidirectional backing, which is applied to the matrix layer during manufacturing. The patch is self-adhesive. In addition to the PRV111 patch, a separately packaged Permeation Enhancer (PE) Powder for Reconstitution used in conjunction with PRV111. The reconstituted PE Solution is intended to improve the absorption of the cisplatin active ingredient and will be applied prior to patch application.

• DrugPRV131 (Cisplatin Intratumoral Injectable)

  PRV131 is a nanoparticle-based cisplatin formulation designed for intratumoral administration. The product is supplied as a lyophilized powder and reconstituted with a separately packaged diluent to form a suspension for injection. The reconstituted suspension is administered directly into the tumor, with dosing customized based on tumor size and injection site distribution. Upon intratumoral administration, the nanoparticles facilitate deep tumor penetration and localized drug release, enabling high local cisplatin concentrations while minimizing systemic exposure.

Outcome measures

Eligibility criteria