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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04471415

Studienbeginn:
August 2020

Letztes Update:
28.05.2021

Wirkstoff:
DRP-104, Atezolizumab

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Dracen Pharmaceuticals, Inc.

Collaborator:
-

Studienleiter

Sunil Sharma, MD
Principal Investigator
HonorHealth Director

Kontakt

Studienlocations
(3 von 9)

Johns Hopkins Kimmel Institute
21231 Baltimore
United StatesRekrutierend» Google-Maps
Mount Sinai Health Systems
10029-6574 New York
United StatesRekrutierend» Google-Maps
University of North Carolina
27514 Chapel Hill
United StatesNoch nicht rekrutierend» Google-Maps
Sarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-Maps
Vanderbilt University Medical Center
37232 Nashville
United StatesRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Maximum Tolerated Dose (MTD (Time Frame - anticipated 1 year):
Safety

2. Area under the plasma concentration versus time curve (AUC) (Time Frame - anticipated 1 year)

3. Cmax of DRP-104 (Time Frame - anticipated 1 year)

Secondary outcome:

1. Overall Response Rate (Time Frame - anticipated 2 year)

2. Disease control rate (Time Frame - anticipated 2 year)

3. Duration of response (Time Frame - anticipated 2 year)

4. Progression-free survival (Time Frame - anticipated 2 year)

5. Overall survival (OS) (Time Frame - anticipated 2 year)

Studien-Arme

  • Experimental: Part 1a & Part 1b
    Single-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
  • Experimental: Part 2
    Cohort 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).
  • Experimental: Part 3
    Dose 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).
  • Experimental: Part 4
    Dose expansion at the MTD of DRP-104 at the selected recommended route of administration (intravenous or subcutaneous) with atezolizumab (N=14 patients).

Geprüfte Regime

  • DRP-104:
    DRP-104 administered intravenously over 1 hour, three times per week (TIW) (Monday, Wednesday, Friday) for 2 consecutive weeks, one week off DRP-104 administered subcutaneously twice weekly (Monday/Thursday or Tuesday/Friday) every week
  • atezolizumab:
    atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.

Quelle: ClinicalTrials.gov


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