Clinical Trials /

First-in-human Study of DRP-104 (Sirpiglenastat) as Single Agent and in Combination With Atezolizumab in Patients With Advanced Solid Tumors.

NCT04471415

Description:

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat) administered via intravenous infusion or via subcutaneous injection as a single agent and in combination with atezolizumab in patients with advanced solid tumors and to assess preliminary safety and efficacy of which route of administration (intravenous or subcutaneous) will be selected for further development for the other two expansions of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations, and advanced squamous cell carcinoma of the head and neck (SCCHN).

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Study of DRP-104 (Sirpiglenastat) as Single Agent and in Combination With Atezolizumab in Patients With Advanced Solid Tumors.
  • Official Title: Phase 1 and Phase 2a, First-in-human Study of DRP-104 (Sirpiglenastat), a Glutamine Antagonist, in Adult Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: DRA-104-001
  • SECONDARY ID: 2020-002770-27
  • NCT ID: NCT04471415

Conditions

  • Advanced Solid Tumor
  • Non-Small Cell Lung Cancer Recurrent
  • Squamous Cell Carcinoma of Head and Neck
  • Non Small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
DRP-104Part 1a & Part 1b
atezolizumabPart 3

Purpose

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat) administered via intravenous infusion or via subcutaneous injection as a single agent and in combination with atezolizumab in patients with advanced solid tumors and to assess preliminary safety and efficacy of which route of administration (intravenous or subcutaneous) will be selected for further development for the other two expansions of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations, and advanced squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description

      This study will be conducted in 4 Parts:

      Part 1: Phase 1 single-agent dose escalation of DRP-104 (sirpiglenastat) in patients with
      advanced solid tumors to define the MTD (up to approximately 50 patients for each intravenous
      and subcutaneous cohort)

      Part 2, Once the MTD of DRP-104 for the IV and subQ route of administration will be
      determined in Part 1, Part 2 will include 2 specific cohorts: Cohort 2 and 3 with one only
      selected formulation. Once the MTD of DRP-104 has been declared for either the IV or suQ
      cohort, Cohort 1 of Part 2 will separately expand for each cohort. -Cohort 1: Phase 1
      single-agent safety expansion at the of DRP-104 in patients with advanced solid tumors (N=
      minimum of 14 and up to 20 patients for each intravenous and subcutaneous cohorts); The
      Sponsor will determine at completion of Phase 1 which route of administration will be further
      developed and continued for all subsequent Cohorts 2 and 3 and Parts 3 and Part 4 in
      combination with atezolizumab.

        -  Cohort 2: Phase 2a expansion at the of DRP-104 in patients with locally advanced or
           metastatic NSCLC whose tumors contain a KEAP1 mutation, NFE2L2 mutation and/or STK11
           mutation (N=55 patients)

        -  Cohort 3: Phase 2a expansion at the MTD of DRP-104 in recurrent, unresectable or
           metastatic SCCHN (N=15-25 patients).

      Part 3: Phase 1 combination dose escalation of DRP-104 (sirpiglenastat) (with either IV or
      subcutaneous formulation selected) and atezolizumab in patients with advanced solid tumors
      previously treated with an anti-PD-1, anti PD-L1, and/or anti-CTLA-4 antibody, starting one
      dose level below the MTD of single-agent DRP-104 and in combination with atezolizumab (up to
      approximately N=12 patients).

      Part 4: Phase 1 combination safety expansion at the MTD of DRP-104 (with either IV or
      subcutaneous formulation selected)with atezolizumab in a similar patient population as the
      dose-escalation (N=14 patients).
    

Trial Arms

NameTypeDescriptionInterventions
Part 1a & Part 1bExperimentalSingle-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 of 3.3 mg/m2 via intravenous injection Single-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 at 10 mg via subcutaneous injection
  • DRP-104
Part 2ExperimentalCohort 1a: Phase 1 single-agent safety expansion at the of intravenous DRP-104 in patients with advanced solid tumors (N=14 up to 20 patients); Cohort 1b: Phase 1 single-agent safety expansion at the of subcutaneous DRP-104 in patients with advanced solid tumors (N=14 up to 20 patients); Cohort 2: Phase 2a expansion at the of DRP-104 at the recommended selected route of administration (intravenous or subcutaneous) in patients with locally advanced or metastatic NSCLC whose tumors contain a KEAP1 mutation, NFE2L2 mutation and/or STK11 mutation (N=55 patients) Cohort 3: Phase 2a expansion at the MTD of DRP-104 at the recommended selected route of administration (intravenous or subcutaneous) in recurrent, unresectable or metastatic SCCHN (N=15-25 patients).
  • DRP-104
Part 3ExperimentalDose escalation of DRP-104 at 1 dose level below declared MTD at the selected recommended route of administration (intravenous or subcutaneous) in combination with atezolizumab in patients with advanced solid tumors previously treated with an anti-PD-1, anti PD-L1, and/or anti-CTLA-4 antibody (up to approximately (N=12 patients).
  • DRP-104
  • atezolizumab
Part 4ExperimentalDose expansion at the MTD of DRP-104 at the selected recommended route of administration (intravenous or subcutaneous) with atezolizumab (N=14 patients).
  • DRP-104
  • atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of advanced or recurrent, histologically or cytologically confirmed,
             measurable by RECIST 1.1 metastatic or unresectable solid tumor

          -  Patient must have progressed on, be intolerant of, decline, or be ineligible for, all
             available standard of care therapies

          -  Part 2: locally advanced or metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation
             ; Patients must have received at least a platinum doublet chemotherapy and an
             anti-PD-(L)1 antibody; Received up to 3 lines of systemic anticancer therapy in the
             recurrent or metastatic setting

          -  Part 2: Recurrent, unresectable or metastatic squamous cell carcinoma of the head and
             neck (SCCHN) (oropharynx, oral cavity, hypopharynx or larynx); Patient must have
             received platinum containing chemotherapy and antiPD-(L)1 antibody in recurrent or
             metastatic setting

          -  Part 3 and 4 - DRP-104 + atezolizumab Prior exposure to any checkpoint inhibitor
             (anti-PD-1, anti-PD-L1, anti-PDL2, and/or anti-CTLA-4 antibody)

          -  ECOG performance 0 or 1

          -  Patient must consent to allow acquisition of existing FFPE tumor tissue; If
             unavailable, patient must consent to new pre-treatment tumor biopsy

          -  All SCCHN patient, all NSCLC patients and all patients treated with combination of
             DRP-104 and atezolizumab will be required to undergo pre-treatment and post-treatment
             core or excisional biopsies.

          -  Pre-treatment and post-treatment core or excisional biopsies are optional for all
             remaining patients

          -  Adequate baseline organ function as defined by: Absolute neutrophil count ≥ 1.5 ×
             109/L (1500/µL); Hemoglobin ≥ 9 g/dL ;Platelets ≥ 75 × 109/L (75,000/µL); Hepatic
             Total bilirubin ≤1.5 × upper limit of normal (ULN): PT/INR and PTT ≤1.5 × ULN, unless
             treated with warfarin; AST(SGOT)/ALT(SGPT) ≤3 × ULN or ≤ 5 × ULN for patients with
             liver metastases; Creatinine clearance ≥ 60 ml/min/1.73m2 measured or calculated

          -  Cardiac QTc (Fridericia) <470 ms

          -  Women of child-bearing potential and men who are sexually active must agree to use one
             highly effective method of contraception

        Exclusion Criteria:

          -  Patients with primary central nervous system tumors and hepatocellular carcinoma

          -  Patients with progressive or symptomatic brain metastases

          -  Leptomeningeal disease

          -  Spinal cord compression not definitively treated with surgery and/or radiation

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage

          -  Prior glutaminase inhibitor use

          -  Prior systemic anticancer treatment (i.e. chemotherapy, biologic therapy, monoclonal
             antibodies, investigational agents) within 21 days or 5 half-lives, whichever is
             shorter

          -  Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks
             prior to enrollment

          -  Prior small port palliative radiotherapy within 14 days of start of Cycle 1

          -  Any major surgery within 21 days from start of Cycle 1

          -  Secondary malignancy that is progressing or has required active treatment within the
             past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have
             undergone potentially curative therapy

          -  Has a known history of HIV, or HBV

          -  Gastrointestinal (GI) function impairment or GI disease

          -  Significant, uncontrolled heart disease and/or cardiac repolarization abnormality

          -  Exclusion specific to only Part 3 and 4 (DRP-104 combined with atezolizumab): History
             of severe allergic, anaphylactic to chimeric or humanized antibodies or fusion
             proteins; Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese
             hamster ovary cells; Prior anti-PD-1, anti-PD-L1 and/or anti CTLA4- agent, patient
             must not have had a serious (> Grade 3) immune-related AE requiring treatment; History
             of autoimmune disease except hypothyroidism on thyroid replacement hormone therapy;
             History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
             pneumonitis; Patients with underlying condition requiring systemic corticosteroids
             (>10 mg daily prednisone equivalents) or other immunosuppressive medications or other
             systemic immunosuppressant medications may be enrolled in the study after approval by
             the Medical Monitor; Evidence or history of active or latent tuberculosis infection;
             Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD
Time Frame:anticipated 1 year
Safety Issue:
Description:Safety

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:anticipated 2 year
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:anticipated 2 year
Safety Issue:
Description:
Measure:Duration of response
Time Frame:anticipated 2 year
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:anticipated 2 year
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:anticipated 2 year
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dracen Pharmaceuticals, Inc.

Last Updated

April 13, 2021