DRP-104 in Patients With NFE2L2/KEAP1-altered Non-Small Cell Lung Cancer

NCT07249372 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-00948
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

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 treatment with chemotherapy and immunotherapy.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR defined as the percentage of participants with a documented response \[complete response (CR) or partial response (PR)\] to the intervention.

  Up to Year 2

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Up to Year 2

• Percentage of Patients with a Best Overall Response (BOR) of CR

  Up to Year 2

• Percentage of Patients with a Best Overall Response (BOR) of PR

  Up to Year 2

• Percentage of Patients with a Best Overall Response (BOR) of SD

  Up to Year 2

• Overall Survival (OS)

  Up to Year 4

Study Arms (1)

NFE2L2/KEAP1-Altered NSCLC

EXPERIMENTAL

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.

Drug: DRP-104

Interventions

DRP-104 DRUG

DRP-104 will be administered subcutaneously (subQ) at a dose of 145mg twice a week (BIW) on a continuous schedule. Once the first dose is administered, the second weekly dose is to be administered 3 days after the first dose with a four-day rest period before the next week of therapy (example, Monday/Thursday or Tuesday/Friday).

NFE2L2/KEAP1-Altered NSCLC

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• years of age or older
• Diagnosis of advanced or recurrent, histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer harboring NFE2L2 or KEAP1 alterations
• Patients must have Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesions
• At the time of enrollment, patients must have experienced progression of disease following treatment with standard of care chemotherapy and immune checkpoint inhibitors either sequentially or concurrently
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Patient should consent to allow the acquisition of existing Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue, as unstained slides, if available or to undergo a fresh tissue biopsy to obtain fresh tumor tissue for performance of correlative studies if deemed feasible. Tumor biopsies should only be performed if deemed safe and feasible by the investigator.
• Adequate baseline organ function:
• a) Absolute neutrophil count (ANC) ≥ 1.5x109/L (1500/uL);
• Without growth factor support for 7 days prior to screening labs for short acting growth factors and 14 days prior to screening labs for long-acting growth factors to meet eligibility
• b) 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)
• c) Platelets \>75x109/L
• No transfusion 7 days prior to screening labs to meet eligibility
• d) Hepatic

You may not qualify if:

• Target disease related 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (2)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Salman Punekar, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salman Punekar, MD

CONTACT

212 731 6228; salman.punekar@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 25, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposes to use the data will be granted access upon reasonable request. Requests should be directed to salman.punekar@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.

Locations

US (2)