ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers

NCT05616624 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202301032
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

In this study, patients with small cell or non-small cell lung cancer will receive ADI-PEG 20, gemcitabine, and docetaxel after demonstrated progression on frontline therapy. In phase I of the study, up to 6 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at that dose level to assess efficacy. Although safety and tolerability has been previously determined in the sarcoma population, dose de-escalations of the chemotherapies in that patient population were required. Therefore, a phase I portion will be incorporated to determine the RP2D of the triplet in this population.

Conditions

Non Small Cell Lung Cancer; Non-small Cell Lung Cancer; Small-cell Lung Cancer; Small Cell Lung Carcinoma

Keywords

Arginine Starvation; ADI-PEG20; SCLC; NSCLCa

Outcome Measures

Primary Outcomes (3)

• Recommended phase II dose (Phase I only)

  -The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first 4 weeks of treatment. Dose escalations will proceed until the MTD has been reached or until Dose Level 3, and this dose level will then be defined as the Recommended Phase 2 Dose (RP2D).

  Through the first 4 weeks of treatment for all Phase I enrolled participants (estimated to be 12 months and 4 weeks)

• Treatment-related serious adverse event (SAE) rate (Phase I only)

  -SAE: an adverse event or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: * Death * A life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect * Any other important medical event that does not fit the criteria above but, based upon appropriate medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above

  From start of treatment through 30 days after completion of treatment (estimated to be 106 weeks)

• Objective response rate (ORR) (Phase II only - compared between non-small cell lung and small cell lung)

  * ORR = percentage of participants with complete response, partial response, or stable disease for 8 cycles * Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  Through completion of treatment (estimated to be 102 weeks)

Secondary Outcomes (4)

• Progression-free survival (PFS) (Phase II only - compared between non-small cell lung and small cell lung)

  Through completion of follow-up (estimated to be up to 362 weeks)

• Overall survival (OS) (Phase II only - compared between non-small cell lung and small cell lung)

  Through completion of follow-up (estimated to be up to 362 weeks)

• Clinical benefit rate (CBR) (Phase II only - compared between non-small cell lung and small cell lung)

  Through completion of treatment (estimated to be 102 weeks)

• Cancer-related mortality rate (Phase II only - compared between non-small cell lung and small cell lung)

  Through completion of follow-up (estimated to be up to 362 weeks)

Study Arms (3)

Phase I: ADI-PEG + gemcitabine + docetaxel

EXPERIMENTAL

* ADI-PEG 20 is given as an intramuscular injection on a weekly basis (Day 1, 8 and 15) at a dose of 36 mg/m\^2. ADI-PEG 20 dosing will start one week prior to the initiation of gemcitabine + docetaxel on Day -7 prior to the initiation of Cycle 1. * Gemcitabine is given intravenously at the assigned dose level on Day 2 of each cycle. * Docetaxel is given intravenously at the assigned dose level on Day 1 of each cycle. * A cycle is defined as 21 days. * After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) per physician discretion or patient request. * Treatment may continue for up to 34 cycles.

Drug: ADI-PEG 20; Drug: Gemcitabine; Drug: Docetaxel

Phase II Non-small cell lung cancer: ADI-PEG + gemcitabine + docetaxel

EXPERIMENTAL

* ADI-PEG 20 is given as an intramuscular injection on a weekly basis (Day 1, 8 and 15) at a dose of 36 mg/m\^2. ADI-PEG 20 dosing will start one week prior to the initiation of gemcitabine + docetaxel on Day -7 prior to the initiation of Cycle 1. * Gemcitabine is given intravenously at the assigned dose level on Day 2 of each cycle. * Docetaxel is given intravenously at the assigned dose level on Day 1 of each cycle. * A cycle is defined as 21 days. * After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) per physician discretion or patient request. * Treatment may continue for up to 34 cycles.

Drug: ADI-PEG 20; Drug: Gemcitabine; Drug: Docetaxel

Phase II Small cell lung cancer: ADI-PEG + gemcitabine + docetaxel

EXPERIMENTAL

* ADI-PEG 20 is given as an intramuscular injection on a weekly basis (Day 1, 8 and 15) at a dose of 36 mg/m\^2. ADI-PEG 20 dosing will start one week prior to the initiation of gemcitabine + docetaxel on Day -7 prior to the initiation of Cycle 1. * Gemcitabine is given intravenously at the assigned dose level on Day 2 of each cycle. * Docetaxel is given intravenously at the assigned dose level on Day 1 of each cycle. * A cycle is defined as 21 days. * After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) per physician discretion or patient request. * Treatment may continue for up to 34 cycles.

Drug: ADI-PEG 20; Drug: Gemcitabine; Drug: Docetaxel

Interventions

ADI-PEG 20 DRUG

-Given 60 minutes (+/- 15 minutes) prior to docetaxel

Also known as: PEGylated arginine deiminase

Phase I: ADI-PEG + gemcitabine + docetaxel; Phase II Non-small cell lung cancer: ADI-PEG + gemcitabine + docetaxel; Phase II Small cell lung cancer: ADI-PEG + gemcitabine + docetaxel

Docetaxel DRUG

-Given over the course of 60 minutes (+/- 10 minutes)

Also known as: Taxotere

Phase I: ADI-PEG + gemcitabine + docetaxel; Phase II Non-small cell lung cancer: ADI-PEG + gemcitabine + docetaxel; Phase II Small cell lung cancer: ADI-PEG + gemcitabine + docetaxel

Gemcitabine DRUG

-Given over the course of 90 minutes (+/- 10 minutes)

Also known as: Gemzar

Phase I: ADI-PEG + gemcitabine + docetaxel; Phase II Non-small cell lung cancer: ADI-PEG + gemcitabine + docetaxel; Phase II Small cell lung cancer: ADI-PEG + gemcitabine + docetaxel

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed extensive stage small cell or metastatic non-small cell lung cancer that has progressed on frontline therapy who are fit for treatment with gemcitabine and docetaxel in the opinion of the treating physician. Phase II enrollment will occur separately to the SCLC and NSCLC cohorts, with up to 36 enrolled in each cohort.
• Measurable disease per RECIST 1.1.
• Treated with at least one previous line of systemic therapy. Specific prior treatment requirements include:
• Patients with ES-SCLC must have been treated with platinum doublet and anti-PD(L)1 therapy, if eligible.
• Patients with NSCLC without a driver mutation must have been treated with platinum doublet and anti-PD(L)1 therapy, if eligible.
• Patients with NSCLC with a driver mutation (EGFR, ALK, ROS1) must have been treated with an FDA approved targeted therapy and platinum doublet therapy, if eligible.
• If the most recent prior line included immunotherapy, patient must have experienced progression by CT scan after cessation of immunotherapy and prior to starting study therapy.
• Patient must have archival tissue available for correlatives. If tissue is not available, approval of enrollment may be granted on a case-by-case basis. Sponsor-investigator approval is required in these instances.
• At least 18 years of age.
• ECOG performance status ≤ 1.
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2 x IULN, patients with Gilberts must be below 3xIULN

You may not qualify if:

• A history of other malignancy with the exception of:
• Malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease
• Basal cell or squamous cell carcinoma of the skin which was treated with local resection only
• Carcinoma in situ of the cervix
• Other tumors discussed with the study PI
• Receipt of any of the following therapies within the below time frames:
• days for chemotherapy
• days or 5 half-lives for an oral small molecule inhibitor (whichever is shorter)
• days for immunotherapy
• days for RT, or 7 days for SBRT or any palliative radiation
• days for surgery
• days for an investigational agent.
• Prior treatment with ADI-PEG 20 or gemcitabine (prior docetaxel is allowed).
• Presence of untreated or unstable brain metastases. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, gemcitabine, pegylated compounds, or other agents used in the study.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Polaris Group: collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

ADI PEG20; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Christine Auberle, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 15, 2022
• Study Start: April 5, 2023
• Primary Completion (Estimated): July 22, 2026
• Study Completion (Estimated): July 22, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)