NextCure Shares Phase 1b Data on NC410 and Pembrolizumab Combo at ASCO 2024

NextCure, Inc., a clinical-stage biopharmaceutical company, has announced promising results from the Phase 1b portion of its Phase 1b/2 clinical study on NC410, a LAIR-2 fusion protein, in combination with pembrolizumab. These findings will be shared at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

The study targeted immune checkpoint inhibitor (ICI) naïve and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer patients. The combination therapy demonstrated noteworthy clinical activity in these challenging cancer types. Dr. Eric S. Christenson, Assistant Professor of Oncology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, will present the data during a poster session.

Key points from the study include the safety and tolerability of NC410 at doses ranging from 30-200 mg combined with 400 mg of pembrolizumab. The combination therapy yielded partial responses (PR) and stable disease in both CRC and ovarian cancer. Most adverse events were mild, classified as Grades 1 and 2.

Michael Richman, President and CEO of NextCure, remarked on the significance of these results. He noted that the combination therapy showed clinical activity against MSS/MSI-L CRC and ovarian cancer, which are typically resistant to immunotherapy. For MSS/MSI-L CRC patients who attained clinical benefits such as partial responses or stable disease after the first scan at nine weeks, disease control was maintained with a median duration of 5.5 months. Richman also highlighted that biomarker data supported NC410's proposed mechanism of action, which involves remodeling the extracellular matrix (ECM) and enhancing immune cell infiltration and activation within the tumor microenvironment (TME). Further results from the ongoing ovarian cancer cohort expansion are anticipated later this year.

Detailed findings from the study are as follows:

- Among 37 evaluable ICI-naïve MSS/MSI-L CRC patients without liver metastasis treated with 100 mg of NC410, there were 2 confirmed ongoing partial responses (lasting 12.5 months and 7.4 months) and 17 patients with stable disease. The median duration of disease control for this cohort was 5.5 months, with a disease control rate (DCR) of 51.3% and an overall response rate (ORR) of 5.4%.
- Of the 7 evaluable ovarian cancer patients in the 100 mg and 200 mg cohorts, there were 3 partial responses. One patient in the 200 mg cohort had a partial response continuing for 7.9 months, while two patients in the 100 mg cohort had partial responses lasting 4.1 months and 5.1 months (ongoing). The DCR and ORR for this cohort were both 43%.
- The most commonly reported adverse events were diarrhea and fatigue. Across all dose levels of NC410 in the Phase 1b portion, 39.5% of patients experienced Grade 3 or higher treatment-emergent adverse events (TEAEs), and 4.9% had Grade 3 or higher treatment-related adverse events (TRAEs). One participant discontinued the study due to Grade 3 myocarditis.

These findings will be presented under the title: "A Phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer," on June 1, 2024, from 9:00 am to 12:00 pm CT during the Developmental Therapeutics—Immunotherapy poster session.

NextCure continues to focus on developing innovative therapies for cancer patients who do not respond to current treatments, leveraging their core strengths in understanding biological pathways and cell interactions within the tumor microenvironment.