Clinical Trials /

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

NCT04291079

Description:

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).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: SRK-181-001
  • NCT ID: NCT04291079

Conditions

  • Cancer

Interventions

DrugSynonymsArms
SRK-181Long Term Extension Phase (LTEP)
anti-PD-(L)1 antibody therapyLong Term Extension Phase (LTEP)

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Part A1: Dose EscalationExperimentalPart 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.
  • SRK-181
Part A2: Dose EscalationExperimentalPart 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.
  • SRK-181
  • anti-PD-(L)1 antibody therapy
Part B: Dose ExpansionExperimentalIn 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.
  • SRK-181
  • anti-PD-(L)1 antibody therapy
Long Term Extension Phase (LTEP)ExperimentalPatients 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
  • SRK-181
  • anti-PD-(L)1 antibody therapy

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of single agent SRK-181
Time Frame:The first 21 days of study treatment
Safety Issue:
Description:Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Maximum drug concentration (Cmax)
Measure: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)
Safety Issue:
Description:Time to Cmax (Tmax)
Measure: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)
Safety Issue:
Description:Last validated plasma concentration (Clast)
Measure: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)
Safety Issue:
Description:Time to Clast (Tlast)
Measure: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)
Safety Issue:
Description:Half-life (t1/2)
Measure: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
Safety Issue:
Description:Objective response, defined as a CR or PR, as determined by RECIST v1.1 or iRECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Scholar Rock, Inc.

Trial Keywords

  • Solid Tumor
  • Metastatic
  • Melanoma
  • Urothelial
  • Non-Small Cell Lung Carcinoma

Last Updated

February 27, 2020