DRP-104 for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Salman Punekar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Glutaminase inhibitors, CYP 3A4/5 inducers

Disqualifiers: Brain metastases, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DRP-104 for patients with non-small cell lung cancer (NSCLC). Researchers aim to evaluate the effectiveness of DRP-104 in patients whose cancer has specific genetic changes (NFE2L2/KEAP1 alterations) and who have already undergone chemotherapy and immunotherapy. Suitable candidates have NSCLC that has progressed despite these previous treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like potent inducers of CYP 3A4/5, and you must have stopped any prior systemic anticancer treatments at least 21 days before starting the trial.

Is there any evidence suggesting that DRP-104 is likely to be safe for humans?

Research has shown that DRP-104 could be a promising treatment for certain types of lung cancer. Studies have found that DRP-104 can reduce tumor size in patients with specific genetic changes. In earlier studies, most patients tolerated DRP-104 well. Some experienced mild side effects, such as fatigue or slight nausea, while serious side effects were rare. Researchers are still testing this treatment to ensure its safety and effectiveness. If trials continue to show positive results, DRP-104 might become a new option for treating lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DRP-104 is unique because it targets tumors with specific genetic alterations in NFE2L2/KEAP1, which aren't specifically addressed by existing treatments like chemotherapy and immunotherapy. Most current treatments for non-small cell lung cancer rely on general approaches to slow cancer growth, but DRP-104 has a novel mechanism that specifically disrupts cancer cell metabolism. Additionally, it is administered subcutaneously on a 21-day cycle without a rest period, potentially offering continuous therapeutic activity and convenience compared to traditional intravenous methods. Researchers are excited about DRP-104's potential to provide a more targeted, effective treatment option for patients with these genetic alterations.

What evidence suggests that DRP-104 might be an effective treatment for non-small cell lung cancer?

Research has shown that DRP-104, a drug that blocks glutamine, can effectively slow tumor growth in non-small cell lung cancer (NSCLC) with specific genetic changes. In this trial, participants with NFE2L2/KEAP1-altered NSCLC will receive DRP-104. The treatment stops cancer cells from using glutamine, which they need to grow, and boosts the body's immune response against the tumor. Early studies found that DRP-104 not only slows cancer growth but also enhances the effectiveness of other treatments, such as immunotherapy. These findings suggest that DRP-104 could be a promising option for patients whose cancer has not responded well to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Salman Punekar, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for individuals with a specific genetic alteration (NFE2L2/KEAP1) in their non-small cell lung cancer. Participants should have already undergone standard chemotherapy and immunotherapy treatments.

Inclusion Criteria

I am 18 years old or older.

My lung cancer is advanced or recurrent and cannot be surgically removed, with specific genetic changes.

My cancer progressed after standard chemotherapy and immunotherapy.

Exclusion Criteria

Patients with progressive or symptomatic brain metastases will be excluded. Patients with brain metastases may be included in this trial as long as the brain metastases have completed definitive treatment at least 14 days prior treatment start and are radiologically stable (i.e., without evidence of progression on screening imaging assessment, [Note: repeat imaging should be performed during study screening]). Patients must be clinically stable and have discontinued anti-seizure medications and steroids, except for physiologic steroid dosing (≤10 mg/day of prednisone equivalents), for at least 14 days prior to Cycle 1 Day 1. Any evidence of leptomeningeal disease Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 8 weeks prior to Cycle 1 Day 1 and must have discontinued steroids, except for physiologic steroid dosing (≤10 mg/day of prednisone equivalents) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); Patients with indwelling catheters (e.g., PleurX) are allowed regardless of drainage frequency Prior therapy 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. Prior glutaminase inhibitor use Prior systemic anticancer treatment (i.e., chemotherapy, biologic therapy [i.e., small molecular inhibitors], monoclonal antibodies, investigational agents]) within 21 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1. If a patient is receiving an anti-PD-1 or anti-PD-L1 antibody on a shorter frequency, i.e., every two weeks, then the patient is eligible if last dose is 14 days prior to Cycle 1 Day 1. Note: 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 palliative radiotherapy within 14 days prior to Cycle 1 Day 1 or within 42 days prior to Cycle 1 Day 1 from definitive local control radiation (any dose greater than 50 Gy, within 42 days of Cycle 1 Day1). Patients must have recovered from all radiation-related toxicities to CTCAE v 5.0 grade 1 or baseline, not require corticosteroids, and not have had radiation pneumonitis. Prior therapy with long-acting myeloid growth factor or from a short acting myeloid growth factor within 14 days or 7 days prior to Cycle 1 Day 1, respectively Any major surgery within 21 days prior to Cycle 1 Day 1 or who have not recovered from side effects of such procedure (CTCAE v 5.0 grade 1 or baseline) Patients receiving potent inducers of CYP 3A4/5 (including St. John's Wort) that cannot be discontinued at least 14 days prior to Cycle 1 Day 1 Medical history and concurrent disease Malignant disease, other than that being treated in this study. Note: Participants with 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 are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1and any malignancy considered indolent and has never required therapy. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required during screening. Impairment of gastrointestinal (GI) function or GI disease that may limit the ability to assess GI associated adverse events (e.g., ulcerative disease, uncontrolled nausea and diarrhea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection) Uncontrolled concurrent illness including, but not limited to: ongoing or active infection; transfusion dependent thrombocytopenia or anemia that prevent meeting hematological inclusion criteria; psychiatric illness/social situations that would limit compliance with study requirements Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: Symptomatic congestive heart failure; Unstable angina pectoris or cardiac arrhythmia; Baseline corrected QTcF (Fridericia) ≥ 470 milliseconds; Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome A known or underlying medical condition that, in the opinion of the investigator or Sponsor, could make the administration of study drug/treatment hazardous to the patient, or could adversely affect the ability of the patient to comply with or tolerate the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous DRP-104 (BIW) on a 21-day cycle with no rest period between cycles but with at least 3 days between injections

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Long-term follow-up

Participants are monitored for overall survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• DRP-104

Trial Overview The study is testing DRP-104, a drug that targets glutamine metabolism, to see if it can help patients with this particular genetic form of lung cancer after they've had the usual treatments.

How Is the Trial Designed?

Group I: NFE2L2/KEAP1-Altered NSCLC Experimental Treatment 1 Intervention

Participants with NFE2L2/KEAP1-altered non-small cell lung cancer previously treated with chemotherapy and immunotherapy will receive subcutaneous DRP-104 (BIW) on a 21-day cycle with no rest period between cycles but with at least 3 days between injections.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10971495/

Glutamine antagonist DRP-104 suppresses tumor growth and ... Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in KEAP1 mutant lung cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07249372

DRP-104 in Patients With NFE2L2/KEAP1-altered Non ... This is a Phase 2 Study of DRP-104, a Glutamine Antagonist, in Patients with NFE2L2/KEAP1-altered Non-Small Cell Lung Cancer following standard of care ...

3. dracenpharma.com dracenpharma.com/wp-content/uploads/2021/04/DRACENposter_AACR2021_03252021-Final.pdf

Broad glutamine pathway inhibition by DRP-104 results in ... ... non-small cell lung cancer (NSCLC) patients1,2. However, the majority of patients who receive CPI or OSI will be either non-responsive to treatment or ...

4. aacrjournals.org aacrjournals.org/mct/article/21/10/1561/709527/Sirpiglenastat-DRP-104-Induces-Antitumor-Efficacy

Sirpiglenastat (DRP-104) Induces Antitumor Efficacy through ... In summary, DRP-104 broadly remodels the tumor microenvironment by inducing extensive tumor metabolism effects and enhancing the infiltration ...

5. biorxiv.org biorxiv.org/content/10.1101/2023.06.27.546750.full

Glutamine antagonist DRP-104 suppresses tumor growth ... We find that DRP-104 suppresses KEAP1 mutant tumor growth by inhibiting glutamine-dependent nucleotide synthesis and promoting anti-tumor CD4 and CD8 T cell ...

6. dana-farber.org dana-farber.org/clinical-trials/22-260

Phase 1 and phase 2a, first-in-human study of DRP-104, a ... The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04471415

NCT04471415 | Study to Investigate DRP-104 in Adults ... The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 ...

8. science.org science.org/doi/10.1126/sciadv.ado7808

Glutamine antagonists may KEAP lung cancer in check These findings indicate that DRP-104 exerts its therapeutic effects in large part by inducing immunity against Keap1-mutant NSCLC.