CAN1012 in Pre-Malignant DCIS and LCIS

A Phase I/Ib Study Evaluating Intralesional TLR7 Agonist, CAN1012, in Pre-malignant Ductal Carcinoma in Situ and Lobular Carcinoma in Situ

This is a Phase I/Ib study evaluating CAN1012 in patients with ductal carcinoma in situ and lobular carcinoma in situ.

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 primary objective of this trial is to examine the safety of CAN1012 delivered by intralesional injection ahead of planned surgical resection. The study will be stopped early for patient safety according to stopping rules below. The sample size for the study is not based on any statistical assumptions. The number of subjects is based on the number of cohorts tested and the size of each cohort.

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.

Inclusion Criteria:

1. Male or female patients with DCIS or LCIS found on core biopsy.

2. Tumor types allowed:

   Biopsy-identified DCIS or LCIS comprising a single lesion ≥ 1 cm and ≤ 5 cm in size by imaging (mammogram or MRI or ultrasound (US)) without evidence of invasive disease on the biopsy and US negative for suspicious ipsilateral lymph nodes.

3. Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 deemed suitable by investigator or designee for requirements of study.

5. 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) ≥ 60.
   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 for people of childbearing potential (bHCG urine or serum)

6. Patients and their partners who are capable of conceiving must agree to use effective methods of contraception (non-hormonal only) 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 known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known history of Hepatitis C virus (defined as HCV RNA) infection. Testing for Hepatitis B and Hepatitis C is not required unless mandated by local health authority.
9. 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.
10. 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.