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Proffered Paper session

1O - Safety, pharmacokinetics, efficacy, and biomarker results of SRK-181 (a latent TGFβ1 inhibitor) from a phase I trial (DRAGON trial)


07 Mar 2023


Proffered Paper session


Clinical Research;  Immunotherapy

Tumour Site


Timothy Yap


Annals of Oncology (2023) 8 (1suppl_2): 100899-100899. 10.1016/esmoop/esmoop100899


T.A. Yap1, J. Gainor2, M. McKean3, B. Bockorny4, M. Barve5, R. Sweis6, U.N. Vaishampayan7, A. Tarhini8, D. Kilari9, A. Chand10, R. Abdul-Karim11, D. Park12, S. Babu13, Y. Ju14, S. Dewall14, L. Liu14, A.M. Kennedy14, J. Marantz14, L. Gan14

Author affiliations

  • 1 The University Of Texas, MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Massachusetts General Hospital, Harvard Medical School, 02114 - Boston/US
  • 3 Drug Development Unit, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 4 Beth Israel Deaconess Medical Center, Harvard University, 02215 - Boston/US
  • 5 Mary Crowley Cancer Research Center, Texas Oncology, 75201 - Dallas/US
  • 6 Department Of Medicine, The University of Chicago, 60637 - Chicago/US
  • 7 Division Of Hematology/ Oncology, Michigan Medicine University of Michigan, 48109 - Ann Arbor/US
  • 8 Cutaneous Oncology And Immunology, H. Lee Moffitt Cancer Center & Research Institute - Magnolia Campus, 33612 - Tampa/US
  • 9 Department Of Medicine, Froedtert Hospital & Medical College of Wisconsin, 53226 - Milwaukee/US
  • 10 Medical Oncology, Innovative Clinical Research Institute, 90033 - Los Angeles/US
  • 11 Department Of Medicine, Henry Ford Cancer Institute-Henry Ford Health, 48202 - Detroit/US
  • 12 Department Of Medicine, Providence St. Jude Medical Center, 92835 - Fullerton/US
  • 13 Medical Oncology, Fort Wayne Medical Oncology and Hematology, 46825 - Fort Wayne/US
  • 14 Clinical Development Dept., Scholar Rock, 02139 - Cambridge/US


This content is available to ESMO members and event participants.

Abstract 1O


SRK-181 is an investigational, fully human, IgG4 monoclonal antibody that selectively binds to latent transforming growth factor-beta 1 (TGFβ1). TGFβ1 activation has been associated with primary resistance to PD-1/PD-L1 [PD-(L)1] blockade. Compared to broad TGFβ inhibitors, SRK-181 was observed to have an improved safety profile (no cardiotoxicities) in 4-week GLP toxicology studies.


NCT04291079 is a multicenter ongoing phase I study with a 3+3 dose escalation design to evaluate SRK-181 in patients (pts) with advanced solid tumors at 80-3000mg q3w and 2000mg q2w (Part A1), and SRK-181 + anti-PD-(L)1 in pts with no response to prior anti-PD-(L)1 therapy at 240-2400mg q3w (Part A2). In Part B, SRK-181 (1500mg q3w or 1000mg q2w) + anti-PD-(L)1 are expanded in anti-PD-(L)1-resistant pts with non-small cell lung cancer, urothelial carcinoma, melanoma, clear cell renal cell carcinoma (ccRCC), or other advanced solid tumors.


As of Dec 2, 2022, the study enrolled 19 pts in Part A1 and 15 in Part A2 with no DLTs observed. The median prior lines of therapies were 4 (range 1-10). In Part A1, the most common treatment-related AEs (TRAEs, >10%) of any grade were fatigue (16%, n=3), decreased appetite and nausea (each 11%, n=2). Best response of stable disease (SD) was observed in 8 pts. All 3 ovarian cancer pts were stable for 25 to 42 weeks. In Part A2, the TRAEs (>10%) of any grade were rash maculo-papular (33%, n=5), pruritus (27%, n=4), rash (20%, n=3), diarrhea and pemphigoid (each 13%, n=2). One confirmed RECIST 1.1 partial response (cPR) was observed at 800mg in a pt with anti-PD-1 resistant ccRCC who stayed on study for 30 weeks. Of 9 pts with best response of SD, 5 were stable >16 weeks. SRK-181 treatment resulted in increased levels of circulatory TGFβ1, indicating target engagement. Part B enrollment is ongoing (N=9 in ccRCC cohort); two cPR were observed in pts with anti-PD-1 resistant ccRCC.


SRK-181 has been tolerated as monotherapy and in combination with anti-PD-(L)1. No DLTs were observed up to 3000mg q3w/2000mg q2w as monotherapy and up to 2400mg q3w as combination treatment. Early signs of efficacy were observed with 3 cPR in pts with anti-PD-1 resistant ccRCC.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Scholar Rock, Inc.


Scholar Rock, Inc.


All authors have declared no conflicts of interest.

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