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

Trial Status: Active

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).

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

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Aaron Lisberg
Phone: 310-794-6500

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE

New York

New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: IN_REVIEW

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE

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 Phase Phase I/II

Trial Type Treatment

Lead Organization
Dracen Pharmaceuticals, Inc.

  • Primary ID DRA-104-001
  • Secondary IDs NCI-2020-06352, 2020-002770-27
  • Clinicaltrials.gov ID NCT04471415