CAN1012 in Pre-malignant Oral Dysplasia

A Phase I/Ib Study Evaluating Intralesional TLR7 Agonist, CAN1012, in Pre-malignant Oral Dysplasia

The primary objective of this trial is to examine the safety of CAN1012 delivered by intralesional injection ahead of planned surgical resection.

Study Overview

• Status: Not yet recruiting
• Conditions: Oral Epithelial Dysplasia (OED)
• Intervention / Treatment: Drug: CAN1012

Detailed Description

This is not a dose finding study, and therefore patients may be enrolled to any of the four arms in any order, based on clinical considerations (e.g. OR scheduling). No arm, per specific disease type, may expand beyond the first 3 patients, until 30-day post-op safety evaluation has been completed. Study analysis is planned after a single dose of intralesional CAN1012.

The Safety Analysis Set will consist of all subjects who receive at least one dose of study treatment. The Safety Analysis Set will be used for safety analyses.

The Intent-to-treat (ITT) Analysis Set will consist of all subjects who receive at least one dose of study treatment and have at least one post-Baseline assessment of tumor response.

The disposition of subjects will be summarized by presenting the number of subjects enrolled, the number and percentage of subjects in each analysis population, the number for whom the study drug was discontinued with the reasons for discontinuation, and the number of subjects who discontinued participation in the study with the reason(s) for withdrawal.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Isa Ngirailemesang, RN; Phone Number: 503-215-1979; Email: canrsrchstudies@providence.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinically-identified oral epithelial dysplasia (OED)
2. Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 deemed suitable by investigator or designee for requirements of study.

4. Laboratory values within 72 hours of Day 0:

   1. WBC ≥ 2.0 K/µL, ANC ≥ 1.0 K/µL
   2. Hgb ≥ 10 g/dL
   3. Platelets ≥ 100,000 K/µL
   4. Creatinine Clearance (using Cockcroft-Gault)
   5. AST/ALT ≤ 2.5 x ULN
   6. Total bilirubin ≤ 3 x ULN, (except subjects with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
   7. Negative pregnancy test (bHCG urine or serum, people of childbearing potential only)
5. Patients and their partners who are capable of conceiving must agree to use effective methods of during the course of treatment and for 165 days after last dose of CAN1012.

Exclusion Criteria:

1. Any serious underlying medical or psychiatric condition that, in the opinion of the investigator, would pose a risk to patient safety or interfere with the study procedures, completion, or evaluation.
2. Need for corticosteroids ≥ 10mg prednisone daily equivalent; inhaled steroids are acceptable.
3. Need for hormonal contraception including oral contraceptives, implant, injectable depots, vaginal rings, skin patches, and the progestin IUD; or any medication that is a sensitive substrate of the major CYPs.
4. History of or current active autoimmune diseases which, in the judgment of the investigator, pose an active and significant risk. Vitiligo, lichen planus or lichenoid inflammation, and adequately controlled endocrine deficiencies such as hypothyroidism/ hyperthyroidism are not exclusionary.
5. Previous history of bone marrow transplantation or oral Graft Versus Host Disease (GVHD).
6. Has an active infection requiring systemic therapy. Investigator may allow if deemed not clinically significant.
7. Has active or uncontrolled Hepatitis B, Hepatitis C, or HIV with AIDS (acquired immunodeficiency syndrome)- defined opportunistic infection.
8. Has a baseline electrocardiogram (ECG) with a prolonged QTc interval > 480 msec. Medications which have a known and clinically significant risk of QT prolongation may be allowed per investigator discretion.
9. Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation, and in the judgment of the investigator still pose an active risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Day 2-3; Injection of CAN1012 into target lesion will occur on Day 0. Specimens collected during Standard of Care (SOC) resection will be evaluated for immunologic changes compared to baseline on Days 2-3.	Drug: CAN1012; CAN1012 is an IFN-α biased, long-acting, highly selective TLR7 agonist, which acts as an immune modulator capable of priming both innate and adaptive immunity against tumors. It has previously been shown on intralesional injection to turn "cold" tumors "hot" through several mechanisms: CAN1012 activates plasmacytoid dendritic cells (pDCs), producing robust IFN-α but minimal IL-6 or TNF;; IFN-α primes NK and CD8+ T cell maturation and release of cytotoxic granules to kill tumor cells;; IFN-α promotes mature cDCs to migrate to tumor draining lymph nodes and present tumor antigens to CD4+ T cells;; Chemokines induced by TLR7 stimulation recruit inflammatory cells into the tumor microenvironment (TME).
Experimental: Arm B: Day 5-7; Injection of CAN1012 into target lesion will occur on Day 0. Specimens collected during Standard of Care (SOC) resection will be evaluated for immunologic changes compared to baseline on Days 5-7.	Drug: CAN1012; CAN1012 is an IFN-α biased, long-acting, highly selective TLR7 agonist, which acts as an immune modulator capable of priming both innate and adaptive immunity against tumors. It has previously been shown on intralesional injection to turn "cold" tumors "hot" through several mechanisms: CAN1012 activates plasmacytoid dendritic cells (pDCs), producing robust IFN-α but minimal IL-6 or TNF;; IFN-α primes NK and CD8+ T cell maturation and release of cytotoxic granules to kill tumor cells;; IFN-α promotes mature cDCs to migrate to tumor draining lymph nodes and present tumor antigens to CD4+ T cells;; Chemokines induced by TLR7 stimulation recruit inflammatory cells into the tumor microenvironment (TME).
Experimental: Arm C: Day 9-11; Injection of CAN1012 into target lesion will occur on Day 0. Specimens collected during Standard of Care (SOC) resection will be evaluated for immunologic changes compared to baseline on Days 9-11.	Drug: CAN1012; CAN1012 is an IFN-α biased, long-acting, highly selective TLR7 agonist, which acts as an immune modulator capable of priming both innate and adaptive immunity against tumors. It has previously been shown on intralesional injection to turn "cold" tumors "hot" through several mechanisms: CAN1012 activates plasmacytoid dendritic cells (pDCs), producing robust IFN-α but minimal IL-6 or TNF;; IFN-α primes NK and CD8+ T cell maturation and release of cytotoxic granules to kill tumor cells;; IFN-α promotes mature cDCs to migrate to tumor draining lymph nodes and present tumor antigens to CD4+ T cells;; Chemokines induced by TLR7 stimulation recruit inflammatory cells into the tumor microenvironment (TME).
Experimental: Arm D: Day 13-15; Injection of CAN1012 into target lesion will occur on Day 0. Specimens collected during Standard of Care (SOC) resection will be evaluated for immunologic changes compared to baseline on Days 13-15.	Drug: CAN1012; CAN1012 is an IFN-α biased, long-acting, highly selective TLR7 agonist, which acts as an immune modulator capable of priming both innate and adaptive immunity against tumors. It has previously been shown on intralesional injection to turn "cold" tumors "hot" through several mechanisms: CAN1012 activates plasmacytoid dendritic cells (pDCs), producing robust IFN-α but minimal IL-6 or TNF;; IFN-α primes NK and CD8+ T cell maturation and release of cytotoxic granules to kill tumor cells;; IFN-α promotes mature cDCs to migrate to tumor draining lymph nodes and present tumor antigens to CD4+ T cells;; Chemokines induced by TLR7 stimulation recruit inflammatory cells into the tumor microenvironment (TME).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Assess safety & tolerability of intralesional CAN1012 injection in subjects with OED by monitoring for adverse events and delays in surgery. Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v6.0 and the Clavien-Dindo grading tool will be used for surgical complications.	Post-operative follow-up visit (30 days after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunologic Monitoring	Flow cytometric analysis on pre/post whole blood, and tandem pre/post Multiplex IF for quantitative immunophenotyping, will be performed to ascertain if TLR7 agonists deplete immunosuppressive immune populations within the tumor and if the multiplex immunofluorescence (mIF) changes in the tumor will not be detectable in peripheral blood.	5 years
LINE-1 Expression	LINE-1 (L1) expression at the protein level will be evaluated using multiplex IF. Paraffin-embedded tissue blocks will be utilized for multiplex IF using the Lunaphore COMET platform.	5 years
Relapse Free Survival (RFS)	Assess whether recurrence of OED or invasive disease (relapse free survival, RFS) within the 5 years of the trial.	5 years

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: CanWell Pharma Inc.
• Investigators: Principal Investigator: Sasha Stanton, MD, PhD, Providence Health & Services

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2033

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2026000210

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No