The combination of SRK-181 and pembrolizumab demonstrated improvements in objective response rate among patients with clear cell renal cell carcinoma in a phase 1 proof-of-concept study.
SRK-181, a selective latent TGFβ1 inhibitor, continues to show promise as a treatment option for patients with clear cell renal cell carcinoma (ccRCC) resistant to anti-PD-1 therapy, according to findings from the phase 1 proof-of-concept DRAGON trial (NCT04291079) presented at the Society for Immunotherapy of Cancer Annual Meeting.1
As of the data cutoff date of August 29, 2023, 6 of 28 evaluable patients treated with SRK-181 and pembrolizumab (Keytruda) who were heavily pretreated had confirmed partial responses and best tumor reduction of 33% to 93%. Stable disease was observed in 10 patients, the disease control rate was 57%, and the objective response rate (ORR) was 21.4%. In the difficult-to-treat ccRCC population, anti-PD-1 retreatment generally results in single-digit ORR or no response, according to Scholar Rock.
Safety was evaluable in 30 patients, and SRK-181 appeared to be well-tolerated in combination with pembrolizumab. There were no observed dose-limiting toxicities (DLTs). One grade 4 treatment-related adverse event (TRAE) of dermatitis exfoliative generalized was seen, and no grade 5 TRAEs were observed. Pemphigoid and rash were observed in 1 patient, immune-related hepatitis was observed in 1 patient, and diarrhea, nausea, and vomiting were all observed in 1 patient.
“The DRAGON trial has successfully delivered on its objective of demonstrating proof of concept for SRK-181 by showing promising anti-tumor activity. These data, along with biomarker results that support proof of mechanism, highlight the immunosuppressive role of TGFβ as a mechanism of anti-PD-1 resistance in patients,” said Jay Backstrom, MD, MPH, president and chief executive officer of Scholar Rock, SRK-181’s manufacturer, in a press release.1
The phase 1, open-label, dose-escalation, and dose-expansion DRAGON trial has an estimated enrollment of 74 patients and an estimated study completion date of December 2024. The primary end points are safety and tolerability of SRK-181 as a monotherapy and in combination with an anti-PD-(L)1 antibody therapy as evaluated by DLTs assessed by investigators. Secondary end points include pharmacokinetics of SRK-181 alone and in combination with anti-PD(L)1 antibody therapy as measured by maximum drug concentration (Cmax), time to Cmax, last validated plasma concentration (Clast), time to Clast, half-life, and objective response.2
SRK-181 is also being investigated in other solid tumor types, including non–small cell lung cancer, urothelial carcinoma, and head and neck squamous cell carcinoma.1
FDA Accepts BLA for Subcutaneous Nivolumab Across Various Solid Tumors
May 6th 2024The FDA is considering a subcutaneous nivolumab formulation for various solid tumors based on promising data from the phase 3 CheckMate -67T trial. A target action date has been set for February 28, 2025.
Read More
Enhancing Precision in Immunotherapy: CD8 PET-Avidity in RCC
March 1st 2024In this episode of Emerging Experts, Peter Zang, MD, highlights research on baseline CD8 lymph node avidity with 89-Zr-crefmirlimab for the treatment of patients with metastatic renal cell carcinoma and response to immunotherapy.
Listen
Tolerability Helps Decide Third-Line Treatment in Advanced RCC
April 30th 2024During a Case-Based Roundtable® Chandler H. Park, MD, led a discussion on the considerations physicians have when deciding on their treatment approach in the third line for patients with advanced renal cell carcinoma in the first article of a 2-part series.
Read More
Sustained Treatment-Free Survival in RCC Seen With Nivolumab and Ipilimumab
April 30th 2024Nivolumab monotherapy plus salvage nivolumab/ipilimumab demonstrated superior treatment-free survival rates among patients with advanced renal cell carcinoma, especially in patients with favorable risk profiles.
Read More