In a single-institution phase I trial reported in JAMA Oncology, Ramalingam et al found that intratumoral injection of pembrolizumab and mRNA-2752 (a combination of interleukin [IL]-23, IL-36γ, and OX40L mRNAs) was active in patients with high-risk ductal carcinoma in situ (DCIS).
Study Details
Ten women were enrolled in the trial at the University of California, San Francisco, between June 2021 and December 2022. Patients had a median tumor size of 5.3 cm (range = 1.0–10.0 cm). Five tumors were hormone receptor [HR]-negative/HER2-positive, two were HR-negative/HER2-negative, two were HR-positive/HER2-negative, and one was HR-positive/HER2-positive. Patients received pembrolizumab at 2 mg to 8 mg and mRNA-2752 at 1 mg to 4 mg intratumorally, with two to four doses given 2 to 3 weeks apart.
Key Findings
Objective response was observed in 8 (80%) of 10 patients, including complete response in 3. All patients with objective response had HER2-positive or HR-negative disease. Three patients with negative posttreatment biopsy results declined surgery and remained disease-free for 1 to 2 years. One patient with a complete response had a 5-mm recurrence at 2 years and was successfully retreated.
High baseline levels of tumor-infiltrating lymphocytes and PD-L1–positive cells were associated with better treatment response.
Adverse events of any grade experienced by all patients up to 1 week after administration included fever, malaise, flu-like symptoms, axillary adenopathy, erythema, injection site swelling, and swelling in the breast. One patient had intermittent urticaria for 3 months. No serious adverse events were observed.
The final recommended combination dose was pembrolizumab at 4 mg with mRNA-2752 at 1 mg.
The investigators concluded: “In this phase 1 nonrandomized clinical trial, the results suggest that intratumoral injections of pembrolizumab and mRNA-2752 are safe and may induce rapid regression of high-risk DCIS with high immune infiltrates. These findings warrant additional investigation, and studies are ongoing.”
Laura J. Esserman, MD, MBA, of the University of California, San Francisco, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, National Cancer Institute, and Moderna. For full disclosures of the study authors, visit jamanetwork.com.
