Scholar Rock Reveals SRK-181 Phase 1 DRAGON Trial Data at ASCO 2024

Scholar Rock, a biopharmaceutical company based in Cambridge, Massachusetts, has revealed promising data from its Phase 1 DRAGON proof-of-concept trial of SRK-181. This trial investigates SRK-181, a selective inhibitor of latent TGFβ1 activation, in combination with pembrolizumab for patients with advanced solid tumors. The data was unveiled during an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 3 in Chicago.

The study reported encouraging responses in patients who had already undergone extensive treatments and were resistant to anti-PD-(L)1 therapy. Scholar Rock's President and CEO, Jay Backstrom, M.D., MPH, highlighted the significance of these findings, noting the potential of SRK-181 to become a crucial component in overcoming immune checkpoint inhibitor resistance. Specifically, the anti-tumor activity in clear cell renal cell carcinoma (ccRCC) and melanoma patients showed considerable promise.

Safety data from the trial indicated that SRK-181 was generally well tolerated when combined with pembrolizumab. Out of 78 patients in the dose expansion phase, the most notable treatment-related adverse event was a Grade 4 case of generalized dermatitis exfoliative in one patient. No Grade 5 treatment-related adverse events were reported, and the most common side effects included rash, pruritis, fatigue, and diarrhea.

The trial's findings provided objective evidence of anti-tumor activity across multiple tumor types, assessed by principal investigators using RECIST 1.1 criteria. The objective response rates (ORR) were particularly notable in ccRCC, with a response rate of 23.3%, and melanoma, with an ORR of 27.3%. These results support the potential of SRK-181 in treating various solid tumors, even in patients who have not responded to other therapies.

Biomarker analyses were conducted on multiple tumor types, focusing on CD8+ T-cell infiltration and regulatory T-cell (Treg) levels. In ccRCC patients, a positive correlation was observed between baseline CD8+ T-cell infiltration and increased response rates. The ORR increased from 23.3% to 40% when patients with baseline CD8+ T-cell infiltration were considered. Additionally, elevated baseline Treg levels in ccRCC patients were associated with an ORR increase to 50%.

These biomarker findings suggest that baseline CD8+ status and Treg levels could serve as potential indicators for selecting patients likely to respond to SRK-181 and anti-PD-(L)1 combination therapy. The ability to predict which patients would benefit most from this treatment could significantly enhance clinical outcomes.

The DRAGON Phase 1 trial also explored various cohorts, including urothelial carcinoma, cutaneous melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, and ccRCC. Scholar Rock's SRK-181 has shown the potential to address the immunosuppressive tumor microenvironment, which is a significant hurdle in cancer therapy.

Scholar Rock continues to engage with the FDA and potential partners to advance this program. The company's commitment to innovative treatments extends beyond oncology, with a focus on neuromuscular diseases, cardiometabolic disorders, and other conditions where protein growth factors are pivotal. Scholar Rock leverages its proprietary platform to develop novel monoclonal antibodies that target protein growth factors selectively, aiming to transform patient care in historically underserved disease areas.

In conclusion, the Phase 1 DRAGON trial data for SRK-181 presents a compelling case for its use in combination with pembrolizumab for treating advanced solid tumors, particularly in anti-PD-(L)1 resistant patients. The promising safety profile and significant anti-tumor activity, supported by biomarker analyses, underscore its potential as a breakthrough in cancer therapy.