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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)

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ClinicalTrials.gov Identifier: NCT04291079
Recruitment Status : Recruiting
First Posted : March 2, 2020
Last Update Posted : June 11, 2020
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 : 183 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 2021
Estimated Study Completion Date : July 2022

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), or other advanced or metastatic solid tumor type that is not NSCLC, UC, or MEL, 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 and Part B:

    • Patient must have a history of primary 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 an anti-PD-(L)1 antibody therapy (alone or in combination with chemotherapy) approved for that tumor type.
    • Patient must have received their most recent dose of anti-PD-(L)1 antibody therapy within 6 months of enrollment.
    • For NSCLC patients who have genomic tumor aberrations for which a targeted therapy is available (e.g., anaplastic lymphoma kinase, EGFR), these patients 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.
  • 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 pregnancy test within 72 hours prior to first administration of SRK-181 and a negative urine pregnancy test on the first day of dosing.
  • WOCBP and males with female partners of child-bearing 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 enrollment.
    • Patient is receiving concurrent anticancer treatment, including anti-PD-(L)1 antibody therapy, either approved or investigational, within 28 days prior to administration of SRK-181.
  • For Part A2 and Part B only:

    • Patient is receiving concurrent anticancer 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 administration 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 administration of SRK-181.
    • Patient has received systemic cytotoxic chemotherapy (except for in combination with anti-PD-(L)1 antibody therapy) <28 days prior to administration of SRK-181.
    • Patient has received targeted small molecule therapy within 5 half-lives of the compound prior to administration 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, Tennessee
Tennessee Oncology, Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37201
Contact: Study Coordinator    615-329-7413      
Principal Investigator: Johanna Bendell, 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         
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: June 11, 2020
Last Verified: June 2020
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
Additional relevant MeSH terms:
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Antibodies
Immunologic Factors
Physiological Effects of Drugs