Study to Investigate DRP-104 in Adults With Advanced Solid Tumors

NCT04471415 | Terminated Phase 1 FDA Drug

• 2 other identifiers: DRA-104-0012020-002770-27
• Study Type: interventional
• Target: 61
• Locations: 5 countries
• Sites: 22

Brief 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 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.

Conditions

Advanced Solid Tumor; Non Small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD)

  Safety

  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

  anticipated 1 year

• Cmax of DRP-104

  Area under the plasma concentration versus time curve (AUC)

  anticipated 1 year

• Overall Response Rate (ORR)

  Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)

  anticipated 2 years

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  anticipated 2 years

• Progression-Free Survival (PFS)

  anticipated 2 years

• Overall Survival (OS)

  anticipated 2 years

Study Arms (4)

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

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.

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);

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).

Drug: DRP-104; Biological: atezolizumab

Interventions

DRP-104 DRUG

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

Part 1a & Part 1b; Part 2; Part 3; Part 4

atezolizumab BIOLOGICAL

atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.

Part 3; Part 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dracen Pharmaceuticals, Inc.: lead

Study Sites (22)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

AdventHealth Medical Group

Kissimmee, Florida, 34747, United States

Location

Florida Cancer Specialist

Orlando, Florida, 32827, United States

Location

Johns Hopkins Kimmel Institute

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029-6574, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

NEXT Oncology

Fairfax, Virginia, 22031, United States

Location

Centrum fur Integrieerte Onkologie

Cologne, 50924, Germany

Location

University Cancer Center NCT

Dresden, 01307, Germany

Location

University Hospital Frankfurt

Frankfurt, 60590, Germany

Location

University Klinikum Wuerzburg

Würzburg, 97070, Germany

Location

National Cancer Center Singapore

Singapore, 169610, Singapore

Location

Hospital University Vall d'Hebron

Barcelona, 08035, Spain

Location

University Hospital 12 de Octubre

Madrid, 28041, Spain

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 37814010 DERIVED

Related Links

• Company website with scientific background on DRP-104

MeSH Terms

Interventions

atezolizumab

Study Officials

• Sunil Sharma, MD

  HonorHealth Director

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, and in combination with atezolizumab cohorts.

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 15, 2020
• Study Start: August 31, 2020
• Primary Completion: March 28, 2023
• Study Completion: March 28, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); DE (4); SG (1); ES (2); TW (2)