First-in-human Study of DRP-104 (Sirpiglenastat) as Single Agent and in Combination With Atezolizumab in Patients With Advanced Solid Tumors.
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ClinicalTrials.gov Identifier: NCT04471415 |
Recruitment Status :
Recruiting
First Posted : July 15, 2020
Last Update Posted : June 22, 2021
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Condition or disease | Intervention/treatment | Phase |
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Advanced Solid Tumor Non-Small Cell Lung Cancer Recurrent Squamous Cell Carcinoma of Head and Neck Non Small Cell Lung Cancer Metastatic | Drug: DRP-104 Biological: atezolizumab | Phase 1 Phase 2 |
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).
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 246 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, SCCHN and combination with atezolizumab cohorts. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | August 31, 2020 |
Estimated Primary Completion Date : | March 2023 |
Estimated Study Completion Date : | December 2023 |

Arm | Intervention/treatment |
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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 |
Drug: 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 |
Experimental: Part 2
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Drug: 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 |
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).
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Drug: 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 Biological: atezolizumab atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks. |
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).
|
Drug: 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 Biological: atezolizumab atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks. |
- Maximum Tolerated Dose (MTD [ Time Frame: anticipated 1 year ]Safety
- Area under the plasma concentration versus time curve (AUC) [ Time Frame: anticipated 1 year ]
- Cmax of DRP-104 [ Time Frame: anticipated 1 year ]
- Overall Response Rate [ Time Frame: anticipated 2 year ]
- Disease control rate [ Time Frame: anticipated 2 year ]
- Duration of response [ Time Frame: anticipated 2 year ]
- Progression-free survival [ Time Frame: anticipated 2 year ]
- Overall survival (OS) [ Time Frame: anticipated 2 year ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04471415
Contact: Margaret Dugan, MD | 973-489-7163 | mdugan@dracenpharma.com | |
Contact: Francois Lafleur, MPH | 917-330-3971 | FLafleur@dracenpharma.com |
United States, Arizona | |
HonorHealth | Recruiting |
Scottsdale, Arizona, United States, 85258 | |
Principal Investigator: Sunil Sharma, MD | |
United States, California | |
UCLA | Recruiting |
Los Angeles, California, United States, 90095 | |
Principal Investigator: Aaron Lisberg, MD | |
United States, Maryland | |
Johns Hopkins Kimmel Institute | Recruiting |
Baltimore, Maryland, United States, 21231 | |
Principal Investigator: Tanguy Siewert, MD | |
United States, New York | |
NYU Langone | Recruiting |
New York, New York, United States, 10016 | |
Principal Investigator: Vamsidhar Velcheti, MD | |
Mount Sinai Health Systems | Recruiting |
New York, New York, United States, 10029-6574 | |
Principal Investigator: Deborah Doroshow, MD | |
United States, North Carolina | |
University of North Carolina | Recruiting |
Chapel Hill, North Carolina, United States, 27514 | |
Principal Investigator: Shetal Patel, MD | |
United States, Tennessee | |
Sarah Cannon Research Institute | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Principal Investigator: Melissa Johnson, MD | |
Vanderbilt University Medical Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Principal Investigator: Michael Gibson, MD | |
Germany | |
Centrum fur Integrieerte Onkologie | Not yet recruiting |
Cologne, Germany, 50924 | |
Contact: MD | |
Principal Investigator: Matthias Scheffler, MD | |
Sub-Investigator: Jurgen Wolfe, MD |
Principal Investigator: | Sunil Sharma, MD | HonorHealth Director |
Responsible Party: | Dracen Pharmaceuticals, Inc. |
ClinicalTrials.gov Identifier: | NCT04471415 |
Other Study ID Numbers: |
DRA-104-001 2020-002770-27 ( EudraCT Number ) |
First Posted: | July 15, 2020 Key Record Dates |
Last Update Posted: | June 22, 2021 |
Last Verified: | May 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Squamous Cell Carcinoma of Head and Neck Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Carcinoma, Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Head and Neck Neoplasms Atezolizumab Antineoplastic Agents |