Clinical trial NCT04291079: SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Solid Tumor
Metastatic
Melanoma
Urothelial
Non-Small Cell Lung Carcinoma
ccRCC
Head and Neck Squamous Cell Carcinoma
Lead sponsor: Scholar Rock, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-02
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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 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.

Primary outcomes:
measure: Safety and tolerability of single agent SRK-181
timeFrame: The first 21 days of study treatment
measure: Safety and tolerability of SRK-181 in combination with anti-PD-(L)1 antibody therapy
timeFrame: The first 21 days of study treatment
Secondary outcomes:
measure: PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy
timeFrame: Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy
timeFrame: Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy
timeFrame: Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy
timeFrame: Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy
timeFrame: Cycle 1 and Cycle 3 (each cycle is 21 days)
measure: Anti-tumor activity of SRK-181, alone or in combination wit anti-PD-(L)1 antibody therapy as potential indicators of clinical response
timeFrame: 6 months
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St. Jude Crosson Cancer Institute
state: California
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: Los Angeles
country: United States
facility: The Oncology Institute
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Celebration
country: United States
facility: Advent Health
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute - South Broward Hospital District
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center& Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology, Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: BUMC Mary Crowley Cancer Research Centers
state: Texas
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ansan-Si
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University - Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Scholar Rock, Inc.
name: Lu Gan, MD
role: STUDY_DIRECTOR
References: