On September 9, 2020 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported that the first patient has been dosed with SRK-181 in combination with anti-PD-(L)1 therapy in Part A2 of the DRAGON Phase 1 proof-of-concept trial (Press release, Scholar Rock, SEP 9, 2020, View Source [SID1234564845]). Part A1 of the DRAGON trial has successfully progressed dose escalation of SRK-181 monotherapy through 800 mg and continues to advance dose escalation . Part A1 and Part A2 are being conducted in a parallel but staggered fashion and will each evaluate doses up to 2400 mg. SRK-181 is a potent and highly selective inhibitor of latent TGFβ1 activation and is being developed to increase responses to immunotherapy by overcoming primary resistance to anti-PD-1 or anti-PD-L1 antibody therapy.
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"We are encouraged by the dose escalation progress-to-date in Part A1 of the DRAGON trial, which has enabled us to begin the evaluation of SRK-181 in combination with anti-PD-(L)1 therapy," said Yung Chyung, M.D., Chief Medical Officer of Scholar Rock. "While checkpoint inhibitor therapies have become standard of care for a large number of cancer patients, there is still significant unmet need as many patients demonstrate resistance to this therapeutic class. It is our belief that SRK-181 could help overcome this immune exclusion and has the potential to increase the therapeutic benefit of this class of drugs."
The DRAGON Phase 1 open-label, dose escalation and dose expansion clinical trial consists of two parts to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SRK-181 in adult patients with locally advanced or metastatic solid tumors enrolled across multiple sites in the U.S. The Part A dose escalation portion of the trial is evaluating SRK-181 as both a single agent (Part A1) and in combination with approved anti-PD-(L)1 therapy (Part A2). The Part B dose expansion portion of the trial is expected to initiate in the first quarter of 2021 and will evaluate SRK-181 in combination with approved anti-PD-(L)1 therapy in multiple tumor-specific cohorts, including urothelial carcinoma, cutaneous melanoma, non-small cell lung cancer, and other solid tumors. As is the case in Part A2, Part B of the trial will enroll patients with locally advanced or metastatic solid tumors who had a lack of response to anti-PD-(L)1 therapy. These patients will be treated with SRK-181 in combination with anti-PD-(L)1 therapy to evaluate if they are able to achieve an anti-tumor response. Intravenous (IV) SRK-181 is administered every 3 weeks (Q3W) and additional dosing regimens may be explored. An update on Part A dose escalation is expected in the fourth quarter of 2020 and efficacy and safety data from Part B of the trial is anticipated starting in 2021.
About SRK-181
SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, data suggests TGFβ1 is a key contributor to excluding immune cell entry into the tumor microenvironment, thereby preventing normal immune function. Scholar Rock believes SRK-181 has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy. By specifically targeting the latent TGFβ1 isoform, Scholar Rock hypothesizes that SRK-181 can increase the therapeutic window by potentially avoiding toxicities associated with non-selective TGFβ inhibition. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.