Combination treatment with MEDI1191 and durvalumab has demonstrated activity in certain patients with advanced solid tumors, according to study results presented at the AACR Annual Meeting 2023.
The combination produced responses in multiple tumor types, and some responses were durable, according to study presenter Eduardo Castañón, MD, of the Clínica Universidad de Navarra in Pamplona, Spain.
Dr Castañón explained that MEDI1191 is an intratumoral interleukin-12 (IL-12) mRNA therapy that promotes local IL-12 production in tumors and drives antitumor immunity via multiple mechanisms.
Researchers evaluated MEDI1191 in combination with durvalumab in an open-label, phase 1 trial (ClinicalTrials.gov Identifier: NCT03946800). The trial enrolled patients with melanoma and breast, colorectal, gastric, pancreatic, head and neck, bladder, non-small cell lung, vulvar, and other cancers.
The trial consisted of a few parts with different treatment regimens and/or lesion locations. In part 1A, 25 patients with subcutaneous or cutaneous lesions received several different doses of MEDI1191 (range, 0.1 µg to 12 µg) on days 1 and 22, followed by durvalumab on days 43, 71, and 99.
In part 1B, 27 patients with subcutaneous or cutaneous lesions received different doses of MEDI1191 (range, 1 µg to 12 µg) concurrently with durvalumab on days 1, 29, 57, and 113, with an additional dose of durvalumab alone on day 85.
In part 1D, 9 patients with deep-seated lesions received 2 different doses of MEDI1191 (0.1 µg or 3 µg) concurrently with durvalumab on days 1, 29, 57, and 113, with an additional dose of durvalumab alone on day 85.
The median age at baseline was 60 years in part 1A, 62 years in part 1B, and 57 years in part 1D. The median number of prior therapies was 6, 4, and 3, respectively.
Safety and Efficacy Results
There were no dose-limiting toxicities, and the maximum tolerated dose was not identified. There were no treatment-related discontinuations or deaths.
Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 41% of patients overall, 44% of those in part 1A, 29.6% of those in part 1B, and 66.7% of those in part 1D. Across all arms, the most common grade 3-4 TEAE was anemia (6.6%).
The objective response rate was 8.2% overall, 4.0% in part 1A, 14.8% in part 1B, and 0% in part 1D. All responses were partial responses. The median duration of response was not reached (range, 1.9-22.3 months).
The disease control rate was 27.9% in the overall cohort, 32.0% for part 1A, and 33.3% for part 1B. None of the patients in part 1D achieved disease control.
Dr Castañón noted that responses were observed in a variety of tumor types. The 7 patients who achieved a partial response had head and neck squamous cell carcinoma, triple-negative breast cancer, pleomorphic sarcoma, nasal neuroendocrine carcinoma, anal melanoma, mucosal/lip melanoma, and acral-lentiginous melanoma.
Dr Castañón also noted that antitumor activity was observed in injected, uninjected, local, and distant lesions. In addition, responses were observed in patients who had received prior anti-PD-1/PD-L1 treatment or anti-CTLA4 treatment.
Disclosures: This research was supported by MedImmune, an AstraZeneca company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Castañón E, Zamarin D, Carneiro BA, et al. Intratumoral (IT) MEDI1191 + durvalumab (D): Update on the first-in-human study in advanced solid tumors. AACR 2023. April 14-19, 2023. Abstract CT004.