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

• ClinicalTrials.gov Identifier: NCT04291079
• Recruitment Status: Recruiting
• First Posted: March 2, 2020
• Last Update Posted: January 10, 2023
• Sponsor: Scholar Rock, Inc.
• Information provided by (Responsible Party): Scholar Rock, Inc.

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

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

Locations

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

Sponsors and Collaborators

Scholar Rock, Inc.

Investigators

• Study Director: Lu Gan, MD; Scholar Rock, Inc.

More Information

• Responsible Party: Scholar Rock, Inc.
• ClinicalTrials.gov Identifier: NCT04291079
• Other Study ID Numbers: SRK-181-001
• First Posted: March 2, 2020
• 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

Keywords provided by Scholar Rock, Inc.:

Solid Tumor; Metastatic; Melanoma; Urothelial; Non-Small Cell Lung Carcinoma; ccRCC

Additional relevant MeSH terms:

Antibodies; Immunologic Factors; Physiological Effects of Drugs