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SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04291079
Recruitment Status : Recruiting
First Posted : March 2, 2020
Last Update Posted : November 21, 2022
Sponsor:
Information provided by (Responsible Party):
Scholar Rock, Inc.

Brief Summary:
This is a multi-center, open-label, Phase 1, first-in-human (FIH), dose-escalation, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 administered alone and in combination with anti-PD-(L)1 therapy in adult patients with locally advanced or metastatic solid tumors. The study is divided into 3 treatment parts (Part A1, Part A2, and Part B) and a Long-Term Extension Phase (LTEP).

Condition or disease Intervention/treatment Phase
Cancer Biological: SRK-181 Biological: anti-PD-(L)1 antibody therapy Phase 1

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.
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.
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:

  • Part A1: Patients may continue treatment with SRK-181 as a single agent at the RP2D in the LTEP following 3 cycles of treatment with SRK-181 as a single agent in Part A1.
  • Part A2: Patients may continue treatment with SRK-181 at the RP2D in combination with anti-PD-(L)1 antibody therapy in the LTEP following 3 cycles of treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy in Part A2.
  • Part B: Patients may continue treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy following 9 cycles of treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy in Part B
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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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.)

  • 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:

  • 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.
  • 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Scholar Rock, Inc. 1-833-SCH-ROCK clinicaltrials@scholarrock.com

Locations
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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, 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         
United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Eugenia Hasenecz, RN    412-623-5253    hasenecze@upmc.edu   
Principal Investigator: Jason Luke, MD, FACP         
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         
Sponsors and Collaborators
Scholar Rock, Inc.
Investigators
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Study Director: Lu Gan, MD Scholar Rock, Inc.
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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: November 21, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Scholar Rock, Inc.:
Solid Tumor
Metastatic
Melanoma
Urothelial
Non-Small Cell Lung Carcinoma
ccRCC
Additional relevant MeSH terms:
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Antibodies
Immunologic Factors
Physiological Effects of Drugs