Advanced Solid TumorPhase 1/2NCT04471415
Study to Investigate DRP-104 in Adults With Advanced Solid Tumors
A Phase 1/2 study testing DRP-104 and atezolizumab in people with Advanced Solid Tumor and Non Small Cell Lung Cancer Metastatic, run by Dracen Pharmaceuticals, Inc. at 22 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Non Small Cell Lung Cancer Metastatic
- What is being tested?
- DRP-104 and atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 31 Aug 2020to 28 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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
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- 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 (patients that require transfusion or growth factors need to demonstrate stable hemoglobin of ≥ 9 g/dL over at least a 7-day period after the last transfusion/growth factor injection prior to screening labs to meet eligibility) ; 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
Who cannot join
- Patients with primary central nervous system tumors and hepatocellular carcinoma
- Patients with progressive or symptomatic brain metastases or leptomeningeal disease
- Patients who have not recovered to grade 1 or baseline from adverse events (CTCAE v 5.0) related to prior therapy excluding alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ grade 3.
- Lymphopenia ≤ grade 3 is allowed if not related to prior anticancer therapy. If related to prior anticancer therapy, lymphopenia must resolve to ≤ grade 1 or baseline.
- Spinal cord compression not definitively treated with surgery and/or radiation
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage
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- 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
- Patients must have recovered from all AEs due to previous therapies to CTCAE v 5.0 grade 1 or baseline, excluding, alopecia, peripheral neuropathy and ototoxicity, which must be at least grade 2 or baseline
- 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, 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
- History of organ transplantation and/or hematopoietic stem cell transplantation
- Evidence or history of active or latent tuberculosis infection
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
Trial locations and contacts
22 sites in 5 countries.
22 sites in 5 countries
United States13 sites
Johns Hopkins Kimmel Institute
Baltimore, Maryland, 21231
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of North Carolina
Chapel Hill, North Carolina, 27514
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
NEXT Oncology
Fairfax, Virginia, 22031
AdventHealth Medical Group
Kissimmee, Florida, 34747
UCLA
Los Angeles, California, 90095
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
NYU Langone
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029-6574
Florida Cancer Specialist
Orlando, Florida, 32827
HonorHealth
Scottsdale, Arizona, 85258
Germany4 sites
Centrum fur Integrieerte Onkologie
Cologne, 50924
University Cancer Center NCT
Dresden, 01307
University Hospital Frankfurt
Frankfurt, 60590
University Klinikum Wuerzburg
Würzburg, 97070
Spain2 sites
Hospital University Vall d'Hebron
Barcelona, 08035
University Hospital 12 de Octubre
Madrid, 28041
Taiwan2 sites
National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 112
About this study
Official title: Phase 1 and Phase 2a, First-in-human Study of DRP-104, a Glutamine Antagonist, in Adult Patients With Advanced Solid Tumors
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 one expansion of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations.
Read the detailed description
This study will be conducted in 4 Parts:
Part 1: Phase 1 single-agent dose escalation of DRP-104 administered via IV infusion (Cohort 1a) or subQ injection (Cohort 1b and 1c) in patients with advanced solid tumors (excluding primary CNS tumors and HCC):
- Cohort 1a: IV DRP-104 dose escalation to define the IV MTD/MAD/RP2D (up to approximately 50 patients)
- Cohort 1b: subQ twice weekly DRP-104 dose escalation to define the twice weekly subQ MTD/MAD/RP2D (up to approximately 50 patients)
- Cohort 1c: subQ thrice weekly DRP-104 dose escalation to define the thrice weekly subQ MTD/MAD/RP2D (up to approximately 12 patients) Upon completion of Part 1, Cohort 1a, 1b, and 1c, the recommended phase 2 route of administration (RP2R: IV or subQ) and schedule of administration (RP2S: twice or thrice weekly) and corresponding MTD/MAD/RP2D will be determined prior to starting Part 2, cohort 2. As of Version 5 of the protocol, further assessment of the intravenous formulation was terminated prior to declaring MTD/MAD/RP2D and the RP2R was determined to be subQ (Section 2.5.5).
Part 2, which opens to enrollment once the MTD/MAD/RP2D/RP2R of DRP-104 has been declared from either Part 1-Cohort 1a, 1b, or 1c and/or the RP2R/RP2S has been determined from Part 1 and includes 2 specific cohorts:
- Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled.
- Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2.
Part 3: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients); The dose of atezolizumab is fixed. Enrollment for Part 3 will begin once at least 14 patients from either Part 1 or 2 have been treated at this dose, route, and schedule for at least one cycle to ensure safety.
Part 4: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).
- Being tested
- DRP-104, atezolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DRP-104Drug
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 OR thrice weekly (Monday, Wednesday, Friday) every week
atezolizumabBiological
atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Part 1a & Part 1b | Experimental | 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 Receives: Drug: DRP-104 |
| Part 2 | Experimental | Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled.
Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2. Receives: Drug: DRP-104 |
| Part 3 | Experimental | Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients); Receives: Drug: DRP-104; Biological: atezolizumab |
| Part 4 | Experimental | Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients). Receives: Drug: DRP-104; Biological: atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Safety
Measured: anticipated 2 year
Pharmacokinetics (PK) of DRP-104
To assess and compare the concentration and partitioning of DRP-104 and the metabolites M1 and DON
Measured: anticipated 1 year
Cmax of DRP-104
Area under the plasma concentration versus time curve (AUC)
Measured: anticipated 1 year
Overall Response Rate (ORR)
Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)
Measured: anticipated 2 years
Secondary outcomes (3)
Disease Control Rate (DCR)
Disease Control Rate of all patient cohorts (months) for IV and SubQ administration
Measured: anticipated 2 years
Progression-Free Survival (PFS)
Using RECIST criteria to assess the time for the disease to progress during treatment with DRP-104 (months)
Measured: anticipated 2 years
Overall Survival (OS)
Defined as the time (months) from the start of treatment to death
Measured: anticipated 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2020
- Study start31 Aug 2020
- Primary completion28 Mar 2023
- Study completion28 Mar 2023
Why it stopped: Company decision to closing study and discontinue further patient enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, and in combination with atezolizumab cohorts.
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dracen Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sunil Sharma, MD, Principal investigator, HonorHealth Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04471415
- Sponsor's protocol ID
- DRA-104-001
- Other IDs
- 2020-002770-27
- Status last verified
- Jun 2023
- First submitted
- 25 Jun 2020
- Last updated
- 12 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Encarnacion-Rosado J, Sohn ASW, Biancur DE, Lin EY, Osorio-Vasquez V, Rodrick T, Gonzalez-Baerga D, Zhao E, Yokoyama Y, Simeone DM, Jones DR, Parker SJ, Wild R, Kimmelman AC. Targeting pancreatic cancer metabolic dependencies through glutamine antagonism. Nat Cancer. 2024 Jan;5(1):85-99. doi: 10.1038/s43018-023-00647-3. Epub 2023 Oct 9.
PubMed 37814010
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 and Phase 2a, First-in-human Study of DRP-104, a Glutamine Antagonist, in Adult Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04471415
- Acronym / sponsor ID
- DRA-104-001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision to closing study and discontinue further patient enrollment.
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Dracen Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 28 Mar 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 15 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 one expansion of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations.
Detailed description
This study will be conducted in 4 Parts:
Part 1: Phase 1 single-agent dose escalation of DRP-104 administered via IV infusion (Cohort 1a) or subQ injection (Cohort 1b and 1c) in patients with advanced solid tumors (excluding primary CNS tumors and HCC):
- Cohort 1a: IV DRP-104 dose escalation to define the IV MTD/MAD/RP2D (up to approximately 50 patients)
- Cohort 1b: subQ twice weekly DRP-104 dose escalation to define the twice weekly subQ MTD/MAD/RP2D (up to approximately 50 patients)
- Cohort 1c: subQ thrice weekly DRP-104 dose escalation to define the thrice weekly subQ MTD/MAD/RP2D (up to approximately 12 patients) Upon completion of Part 1, Cohort 1a, 1b, and 1c, the recommended phase 2 route of administration (RP2R: IV or subQ) and schedule of administration (RP2S: twice or thrice weekly) and corresponding MTD/MAD/RP2D will be determined prior to starting Part 2, cohort 2. As of Version 5 of the protocol, further assessment of the intravenous formulation was terminated prior to declaring MTD/MAD/RP2D and the RP2R was determined to be subQ (Section 2.5.5).
Part 2, which opens to enrollment once the MTD/MAD/RP2D/RP2R of DRP-104 has been declared from either Part 1-Cohort 1a, 1b, or 1c and/or the RP2R/RP2S has been determined from Part 1 and includes 2 specific cohorts:
- Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled.
- Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2.
Part 3: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients); The dose of atezolizumab is fixed. Enrollment for Part 3 will begin once at least 14 patients from either Part 1 or 2 have been treated at this dose, route, and schedule for at least one cycle to ensure safety.
Part 4: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, and in combination with atezolizumab cohorts.
| Arm | Type | Receives |
|---|---|---|
| Part 1a & Part 1b | Experimental | Drug: DRP-104Single-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 |
| Part 2 | Experimental | Drug: DRP-104Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled. Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2. |
| Part 3 | Experimental | Drug: DRP-104, Biological: atezolizumabPhase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients); |
| Part 4 | Experimental | Drug: DRP-104, Biological: atezolizumabPhase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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 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
Key exclusion criteria (25 listed)
- Patients with primary central nervous system tumors and hepatocellular carcinoma
- Patients with progressive or symptomatic brain metastases or leptomeningeal disease
- Patients who have not recovered to grade 1 or baseline from adverse events (CTCAE v 5.0) related to prior therapy excluding alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ grade 3.
- Lymphopenia ≤ grade 3 is allowed if not related to prior anticancer therapy. If related to prior anticancer therapy, lymphopenia must resolve to ≤ grade 1 or baseline.
- Spinal cord compression not definitively treated with surgery and/or radiation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DRP-104DRP-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 OR thrice weekly (Monday, Wednesday, Friday) every week | Drug | Part 1a & Part 1b, Part 2, Part 3, Part 4 |
| atezolizumabatezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks. | Biological | Part 3, Part 4 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: anticipated 2 year
Safety
Pharmacokinetics (PK) of DRP-104
Time frame: anticipated 1 year
To assess and compare the concentration and partitioning of DRP-104 and the metabolites M1 and DON
Cmax of DRP-104
Time frame: anticipated 1 year
Area under the plasma concentration versus time curve (AUC)
Overall Response Rate (ORR)
Time frame: anticipated 2 years
Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)
3 secondary outcomes
Disease Control Rate (DCR)
Time frame: anticipated 2 years
Progression-Free Survival (PFS)
Time frame: anticipated 2 years
Overall Survival (OS)
Time frame: anticipated 2 years
Results and safety
The study was stopped early (reason given: Company decision to closing study and discontinue further patient enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Derived from this study: PubMed 37814010Encarnacion-Rosado J, Sohn ASW, Biancur DE, Lin EY, Osorio-Vasquez V, Rodrick T, Gonzalez-Baerga D, Zhao E, Yokoyama Y, Simeone DM, Jones DR, Parker SJ, Wild R, Kimmelman AC. Targeting pancreatic cancer metabolic dependencies through glutamine antagonism. Nat Cancer. 2024 Jan;5(1):85-99. doi: 10.1038/s43018-023-00647-3. Epub 2023 Oct 9.
- Company website with scientific background on DRP-104Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sunil Sharma, MD principal investigator
HonorHealth Director
22 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DRP-104 and atezolizumab in people with Advanced Solid Tumor and Non Small Cell Lung Cancer Metastatic, run by Dracen Pharmaceuticals, Inc. at 22 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Germany, Spain, Taiwan, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Company decision to closing study and discontinue further patient enrollment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: anticipated 2 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04471415, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.