SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON)
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ClinicalTrials.gov Identifier: NCT04291079 |
Recruitment Status :
Recruiting
First Posted : March 2, 2020
Last Update Posted : January 10, 2023
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Condition or disease | Intervention/treatment | Phase |
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Cancer | Biological: SRK-181 Biological: anti-PD-(L)1 antibody therapy | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 200 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1, Open-Label, Dose-Escalation, and Dose-Expansion Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of SRK-181 Alone and in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) |
Actual Study Start Date : | April 23, 2020 |
Estimated Primary Completion Date : | December 2023 |
Estimated Study Completion Date : | December 2024 |

Arm | Intervention/treatment |
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Experimental: Part A1: Dose Escalation
Part A1 will determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of SRK-181 as a single agent and will determine the recommended Phase 2 dose (RP2D) of SRK-181 as a single-agent.
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Biological: SRK-181
anti-latent TGFβ1 monoclonal antibody |
Experimental: Part A2: Dose Escalation
Part A2 will determine the MTD or MAD of SRK-181 in combination with anti-PD-(L)1 antibody therapy and will determine the RP2D of SRK-181 in combination with anti-PD-(L)1 antibody therapy for use in Part B.
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Biological: SRK-181
anti-latent TGFβ1 monoclonal antibody Biological: anti-PD-(L)1 antibody therapy approved anti-PD-(L)1 antibody therapy for each tumor type |
Experimental: Part B: Dose Expansion
In Part B, parallel cohorts of patients with Non-small cell lung cancer (NSCLC), Urothelial Carcinoma (UC), Cutaneous melanoma (MEL), clear cell Renal cell carcinoma (ccRCC) or other advanced or metastatic solid tumor type that is not NSCLC, UC, MEL, or ccRCC will be enrolled to confirm the tolerability of the RP2D of SRK-181 (determined in Part A2) and to evaluate the anti-tumor activity of SRK-181 in combination with an anti-PD-(L)1 antibody therapy.
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Biological: SRK-181
anti-latent TGFβ1 monoclonal antibody Biological: anti-PD-(L)1 antibody therapy approved anti-PD-(L)1 antibody therapy for each tumor type |
Experimental: Long Term Extension Phase (LTEP)
Patients may continue treatment in a LTEP:
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Biological: SRK-181
anti-latent TGFβ1 monoclonal antibody Biological: anti-PD-(L)1 antibody therapy approved anti-PD-(L)1 antibody therapy for each tumor type |
- Safety and tolerability of single agent SRK-181 [ Time Frame: The first 21 days of study treatment ]Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness
- Safety and tolerability of SRK-181 in combination with anti-PD-(L)1 antibody therapy [ Time Frame: The first 21 days of study treatment ]Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness
- PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy [ Time Frame: Cycle 1 and Cycle 3 (each cycle is 21 days) ]Maximum drug concentration (Cmax)
- PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy [ Time Frame: Cycle 1 and Cycle 3 (each cycle is 21 days) ]Time to Cmax (Tmax)
- PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy [ Time Frame: Cycle 1 and Cycle 3 (each cycle is 21 days) ]Last validated plasma concentration (Clast)
- PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy [ Time Frame: Cycle 1 and Cycle 3 (each cycle is 21 days) ]Time to Clast (Tlast)
- PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy [ Time Frame: Cycle 1 and Cycle 3 (each cycle is 21 days) ]Half-life (t1/2)
- Anti-tumor activity of SRK-181, alone or in combination wit anti-PD-(L)1 antibody therapy as potential indicators of clinical response [ Time Frame: 6 months ]Objective response, defined as a CR or PR, as determined by RECIST v1.1 or iRECIST v1.1

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Patient has a histologically documented solid tumor that is metastatic or locally advanced, for which SoC therapy does not exist, has failed in the patient, or is not tolerated by the patient, or for which the patient has been assessed by the Investigator as not being a suitable candidate or otherwise ineligible for the SoC therapy.
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For Part A2:
o Patient must have a history of anti-PD-(L)1 antibody nonresponse presenting (based upon the Investigator's assessment) either as progressive disease or stable disease (e.g., not improving, but also not worsening, clinically or radiographically) after at least 3 cycles of treatment with the most recent anti-PD-(L)1 antibody therapy (alone or in combination with chemotherapy) approved for that tumor type. (Note: if the duration of prior anti-PD-1 therapy is shorter than 3 cycles and the reason for discontinuation is progressive disease, the progression should be associated with clinical deterioration.)
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For Part B Cohort NSCLC, UC, MEL and ccRCC:
- Patient must be diagnosed with one of the following disease-specific solid tumors of NSCLC, UC, or MEL, and must have a history of primary nonresponse to anti-PD-1 therapy (alone or in combination with other therapy), presenting the best response (based upon the Investigator's assessment) either as progressive disease or stable disease (e.g., not improving, but also not worsening, clinically or radiographically) after at least 3 cycles of treatment.
- For Cohort NSCLC, patients who have genomic tumor aberrations for which a targeted therapy is available (e.g., anaplastic lymphoma kinase, EGFR) must have progressed on an approved therapy for these aberrations or did not tolerate an approved therapy for these aberrations, or were not considered suitable candidates/ were otherwise ineligible for an approved therapy for these aberrations.
- For Cohort ccRCC, patients must have a histologically confirmed diagnosis of RCC with a predominant clear cell component and must have received at least 1 prior line of anti-PD-1 treatment (alone or in combination with other therapy) and have had disease progression clinically or radiographically on the most recent anti-PD-1 treatment
- Up to 3 lines of treatment are allowed between the last dose of anti-PD-1 and enrollment.
- For Part B Cohort Any Other: Patient must be diagnosed with any other solid tumor type that is not NSCLC, UC, MEL, or ccRCC for which the patient has had a history of primary anti PD (L)1 antibody nonresponse, presenting the best response (based upon the Investigator's assessment) as progressive disease, after prior anti-PD-(L)1 antibody therapy (alone or in combination with other therapy) currently approved for that tumor indication
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed at Screening.
- Patient must have an Eastern Cooperative Oncology Group performance status (PS) 0-1.
- Patient must have a predicted life expectancy of ≥ 3 months.
- Women of child-bearing potential (WOCBP) must have a negative urine or serum pregnancy test up to 24 hours prior to first dose of SRK-181.
- WOCBP and males with female partners of childbearing potential must agree to use adequate birth control throughout their participation and for 90 days following the last dose of SRK-181.
Key Exclusion Criteria:
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For Part A1 only:
- Patient has had anti-PD-(L)1 antibody therapy ≤ 28 days prior to the first dose of SRK-181.
- Patient is receiving concurrent anti-cancer treatment, including anti-PD-(L)1 antibody therapy, either approved or investigational, within 28 days prior to the first dose of SRK-181.
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For Part A2 and Part B only:
- Patient is receiving concurrent anti-cancer treatment, with the exception of an anti-PD-(L)1 antibody therapy for Part A2 or Part B, either approved or investigational, within 28 days prior to the first dose of SRK-181.
- Patient has received biologic therapy (except for anti-PD-(L)1 antibody therapy for Part A2 or Part B), <28 days prior to the first dose of SRK-181.
- Patient has received systemic cytotoxic chemotherapy (except for in combination with anti-PD-(L)1 antibody therapy) <28 days prior to the first dose of SRK-181.
- Patient has received targeted small molecule therapy within 5 half-lives of the compound prior to the first dose of SRK-181.
- Patient has a history of intolerance or treatment discontinuation due to severe irAE or other adverse reaction from prior anti-PD-(L)1 antibody therapy.
- Patient has a hypersensitivity to anti-PD-(L)1 antibody therapy.
- Patient has the documented presence of neutralizing ADA to anti-PD-(L)1 antibody therapy.
- Patient has a diagnosis of immunodeficiency, either primary or acquired.
- Patient is symptomatic or has uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
- Patient has current second malignancy at other sites (exceptions: adequately treated in situ carcinoma [e.g., cervical], non-MEL skin cancer, bilateral synchronous discordant breast cancer, or indolent prostate cancer under observation). A past history of other malignancies is allowed as long as patient has been free of recurrence for ≥ 2 years, or if the patient has been treated with curative intent within the past 2 years and, in the opinion of the Investigator, is unlikely to have a recurrence.
- Women who are pregnant or breastfeeding.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04291079
Contact: Scholar Rock, Inc. | 1-833-SCH-ROCK | clinicaltrials@scholarrock.com |
United States, California | |
St. Jude Crosson Cancer Institute | Recruiting |
Fullerton, California, United States, 92835 | |
Contact: Linda Gozar, MPH 714-446-5177 | |
Principal Investigator: David J Park, MD | |
Innovative Clinical Research Institute | Recruiting |
Los Angeles, California, United States, 90603 | |
Contact: Leslie Posadas 562-693-4477 leslieposadas@theoncologyinstitute.com | |
Principal Investigator: Arati Chand, MD | |
United States, Florida | |
H. Lee Moffitt Cancer Center& Research Institute | Recruiting |
Tampa, Florida, United States, 33612 | |
Contact: Karina Gonzalez Bonilla, MPH, BSN, BS 813-745-3246 karina.gonzalezbonilla@moffitt.org | |
Principal Investigator: Ahmad Tarhini, MD, PhD | |
United States, Illinois | |
University of Chicago | Recruiting |
Chicago, Illinois, United States, 60637 | |
Contact: Eli Gussen 773-702-4193 gussene@medicine.bsd.uchicago.edu | |
Principal Investigator: Randy Sweis, MD | |
United States, Indiana | |
Fort Wayne Medical Oncology and Hematology, Inc | Active, not recruiting |
Fort Wayne, Indiana, United States, 46804 | |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02115 | |
Contact: Justin L Gainor, MD 617-724-4000 jgainor@partners.org | |
Principal Investigator: Justin L Gainor, MD | |
Beth Israel Deaconess Medical Center | Recruiting |
Boston, Massachusetts, United States, 02155 | |
Contact: Bruno Bockorny, MD 617-667-2100 Bbockorny@bidmc.harvard.edu | |
Principal Investigator: Bruno Bockorny, MD | |
United States, Michigan | |
University of Michigan | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: MET-Referrals MET-Referrals@med.umich.edu | |
Principal Investigator: Ulka Vaishampayan, MD | |
Henry Ford Cancer Institute | Recruiting |
Detroit, Michigan, United States, 48202 | |
Contact: Andrew Anastos 313-725-7858 aanasto1@hfhs.org | |
Principal Investigator: Raghad Abdul-Karim, MD | |
United States, Pennsylvania | |
UPMC Hillman Cancer Center | Withdrawn |
Pittsburgh, Pennsylvania, United States, 15232 | |
United States, Tennessee | |
Tennessee Oncology, Sarah Cannon Research Institute | Recruiting |
Nashville, Tennessee, United States, 37201 | |
Contact: Study Coordinator 615-329-7413 | |
Principal Investigator: Meredith McKean, MD | |
United States, Texas | |
BUMC Mary Crowley Cancer Research Centers | Recruiting |
Dallas, Texas, United States, 75230 | |
Contact: Study Coordinator 214-658-1944 | |
Principal Investigator: Minal Barve, MD | |
The University of Texas - MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Timothy Yap, MD 713-563-1930 | |
Principal Investigator: Timothy Yap, MD | |
United States, Wisconsin | |
Medical College of Wisconsin | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Contact: Cassandra Kujawa 414-805-8839 ckujawa@mcw.edu | |
Contact: Jaydah Gonzalez Jaydgonzalez@mcw.edu | |
Principal Investigator: Deepak Kilari, MD |
Study Director: | Lu Gan, MD | Scholar Rock, Inc. |
Responsible Party: | Scholar Rock, Inc. |
ClinicalTrials.gov Identifier: | NCT04291079 |
Other Study ID Numbers: |
SRK-181-001 |
First Posted: | March 2, 2020 Key Record Dates |
Last Update Posted: | January 10, 2023 |
Last Verified: | January 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Solid Tumor Metastatic Melanoma |
Urothelial Non-Small Cell Lung Carcinoma ccRCC |
Antibodies Immunologic Factors Physiological Effects of Drugs |