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

NCT04291079 | Completed Phase 1 FDA Drug

• 1 other identifier: SRK-181-001
• Study Type: interventional
• Target: 112
• Locations: 2 countries
• Sites: 22

Brief Summary

This was 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 was divided into 3 treatment parts (Part A1, Part A2, and Part B) and a Long-Term Extension Phase (LTEP).

Conditions

Cancer

Keywords

Solid Tumor; Metastatic; Melanoma; Urothelial; Non-Small Cell Lung Carcinoma; ccRCC; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of single agent SRK-181

  Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness

  The first 21 days of study treatment

• Safety and tolerability of SRK-181 in combination with anti-PD-(L)1 antibody therapy

  Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness

  The first 21 days of study treatment

Secondary Outcomes (6)

• PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy

  Cycle 1 and Cycle 3 (each cycle is 21 days)

• PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy

  Cycle 1 and Cycle 3 (each cycle is 21 days)

• PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy

  Cycle 1 and Cycle 3 (each cycle is 21 days)

• PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy

  Cycle 1 and Cycle 3 (each cycle is 21 days)

• PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy

  Cycle 1 and Cycle 3 (each cycle is 21 days)

Study Arms (4)

Part A1: Dose Escalation

EXPERIMENTAL

Part A1 determined the maximum tolerated dose (MTD) or maximum administered dose (MAD) of SRK-181 as a single agent and the recommended Phase 2 dose (RP2D) of SRK-181 as a single-agent.

Biological: SRK-181

Part A2: Dose Escalation

EXPERIMENTAL

Part A2 determined the MTD or MAD of SRK-181 in combination with anti-PD-(L)1 antibody therapy and the RP2D of SRK-181 in combination with anti-PD-(L)1 antibody therapy for use in Part B.

Biological: SRK-181; Biological: anti-PD-(L)1 antibody therapy

Part B: Dose Expansion

EXPERIMENTAL

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), Head and Neck Squamous Cell Carcinoma (HNSCC), or other advanced or metastatic solid tumor type that is not NSCLC, UC, MEL, or ccRCC were 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; Biological: anti-PD-(L)1 antibody therapy

Long Term Extension Phase (LTEP)

EXPERIMENTAL

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; Biological: anti-PD-(L)1 antibody therapy

Interventions

SRK-181 BIOLOGICAL

anti-latent TGFβ1 monoclonal antibody

Long Term Extension Phase (LTEP); Part A1: Dose Escalation; Part A2: Dose Escalation; Part B: Dose Expansion

anti-PD-(L)1 antibody therapy BIOLOGICAL

approved anti-PD-(L)1 antibody therapy for each tumor type

Long Term Extension Phase (LTEP); Part A2: Dose Escalation; Part B: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 HNSCC:
• Patients must have a histologically confirmed diagnosis of recurrent or metastatic HNSCC that is non-amendable to curative therapy (e.g., radiation or surgery).
• The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible.
• Patients must have received one prior line of anti-PD-1 treatment (alone or in combination with other therapy) and have had disease progression clinically or radiographically on the anti-PD-1 treatment.
• Up to one line of treatment are allowed between the last dose of anti-PD-1 and enrollment.
• For patients with primary oropharyngeal cancer, patients must have results from testing of human papillomavirus (HPV) or P16 status.
• For Part B Cohort Any Other (enrollment complete): 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Scholar Rock, Inc.: lead

Study Sites (22)

St. Jude Crosson Cancer Institute

Fullerton, California, 92835, United States

Location

University of California - San Diego

La Jolla, California, 92093, United States

Location

The Oncology Institute

Los Angeles, California, 90603, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Advent Health

Celebration, Florida, 34747, United States

Location

Memorial Cancer Institute - South Broward Hospital District

Hollywood, Florida, 33021, United States

Location

H. Lee Moffitt Cancer Center& Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02155, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794, United States

Location

Tennessee Oncology, Sarah Cannon Research Institute

Nashville, Tennessee, 37201, United States

Location

BUMC Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Korea University Ansan Hospital

Ansan-si, 92093, South Korea

Location

Seoul National University - Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Related Publications (1)

• Yap TA, Sweis RF, Vaishampayan U, Kilari D, Gainor JF, McKean M, Barve M, Tarhini AA, Bockorny B, Sonpavde G, Park D, Babu S, Ju Y, Liu L, Henry S, Tirucherai GS, DeWall S, Qatanani M, Marantz JL, Gan L. Linavonkibart and pembrolizumab in immune checkpoint blockade-resistant advanced solid tumors: a phase 1 trial. Nat Med. 2026 Jan 13. doi: 10.1038/s41591-025-04157-w. Online ahead of print.

  PMID: 41530380 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

SRK-181

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Study Officials

• Lu Gan, MD

  Scholar Rock, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 2, 2020
• Study Start: April 23, 2020
• Primary Completion: April 14, 2025
• Study Completion: April 14, 2025
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4); US (18)