KEY TAKEAWAYS
- The phase 1 DRAGON study assessed SRK-181 and SRK-181+anti-PD-(L)1 in dose escalation (Part A) and SRK-181 (1500mg q3w)+pembrolizumab in anti-PD-1 resistant patients across various cancers (Part B).
- As of May 26, 2023, SRK-181 combined with pembrolizumab showed a 25% objective response rate and 69% clinical benefit in anti-PD-1-refractory ccRCC patients.
SRK-181 is a fully human IgG4 monoclonal antibody focused on latent TGFβ1. It is being studied alone or in conjunction with anti-PD-(L)1 therapy to counteract resistance to immune checkpoint inhibition.
The DRAGON study (NCT04291079), an open-label phase 1 trial, assessed SRK-181’s efficacy. Part A examined SRK-181 and SRK-181+anti-PD-(L)1. Part B administered SRK-181 (1500mg q3w)+pembrolizumab to anti-PD-1 resistant patients (pts) with various cancers.
As of May 26, 2023, the study enrolled 20 metastatic ccRCC pts who were resistant to anti-PD-1 therapy (2 in Part A2, 18 in Part B). They had undergone a median of 3 prior treatment lines (ranging from 1 to 6), including both tyrosine kinase inhibitors and anti-PD-1 therapy.
Previous responses to anti-PD-1 therapy ranged from stable disease (SD) to disease progression (PD), with all pts showing progression later. Among the 20 patients (16 males, 4 females; median age 59), the most common treatment-related side effects (>10%) were pruritus (15%, n=3), maculo-papular rash (15%, n=3), and rash (10%, n=2). No severe (grade 4 or 5) treatment-related side effects occurred, though immune-mediated hepatitis, pemphigoid, and rash were noted as serious adverse events (n=1 each).
Sixteen patients were evaluated for response, with 4 achieving confirmed partial response (PR) as per RECIST1.1 criteria by PI assessment (Overall Response Rate = 25%).
These 4 pts, previously treated with 2 to 5 therapies, experienced tumor reduction ranging from -50% to -84% and continued the study for 5+ to 14+ months. Seven patients had stable disease (SD), with four still participating for 2+ to 8+ months.
While biomarker data will be further shared, initial findings suggest that the treatment decreased levels of circulatory myeloid-derived suppressor cells below baseline by Day 30 post-treatment.
In the initial findings, the combination therapy involving SRK-181 and anti-PD-1 drug (pembrolizumab) showed good tolerance among heavily treated ccRCC patients resistant to anti-PD-1 therapy, achieving a 25% Overall Response Rate (ORR) and a clinical benefit rate of 69%. Enrollment for all patient groups is still ongoing.
Source: https://jitc.bmj.com/content/11/Suppl_1/A756
Clinical Trial: https://clinicaltrials.gov/study/NCT04291079
Yap T, Vaishampayan UN, Kilari D, et al666 Safety, efficacy, and biomarker results of SRK-181, a latent TGFβ1 inhibitor, in anti-PD-1 resistant metastatic ccRCC patientsJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0666.
