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

Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04291079
• Other study ID #: SRK-181-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 23, 2020
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Scholar Rock, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

• 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.

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• SRK-181
anti-latent TGFß1 monoclonal antibody
• anti-PD-(L)1 antibody therapy
approved anti-PD-(L)1 antibody therapy for each tumor type

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan-Si
Korea, Republic of	Seoul National University - Bundang Hospital	Seongnam-si
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
United States	University of Michigan	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Advent Health	Celebration	Florida
United States	University of Chicago	Chicago	Illinois
United States	BUMC Mary Crowley Cancer Research Centers	Dallas	Texas
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Fort Wayne Medical Oncology and Hematology, Inc	Fort Wayne	Indiana
United States	St. Jude Crosson Cancer Institute	Fullerton	California
United States	Memorial Cancer Institute - South Broward Hospital District	Hollywood	Florida
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of California - San Diego	La Jolla	California
United States	The Oncology Institute	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology, Sarah Cannon Research Institute	Nashville	Tennessee
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	H. Lee Moffitt Cancer Center& Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Scholar Rock, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy	Maximum drug concentration (Cmax)	Cycle 1 and Cycle 3 (each cycle is 21 days)
Secondary	PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy	Time to Cmax (Tmax)	Cycle 1 and Cycle 3 (each cycle is 21 days)
Secondary	PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy	Last validated plasma concentration (Clast)	Cycle 1 and Cycle 3 (each cycle is 21 days)
Secondary	PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy	Time to Clast (Tlast)	Cycle 1 and Cycle 3 (each cycle is 21 days)
Secondary	PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy	Half-life (t1/2)	Cycle 1 and Cycle 3 (each cycle is 21 days)
Secondary	Anti-tumor activity of SRK-181, alone or in combination wit anti-PD-(L)1 antibody therapy as potential indicators of clinical response	Objective response, defined as a CR or PR, as determined by RECIST v1.1 or iRECIST v1.1	6 months