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

The Washington University

Status and phase: Enrolling; Phase 2; Phase 1

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

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05616624

202301032

Details and patient eligibility

About

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.

Enrollment: 114 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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. The allowable window between treatments is 21 days for chemotherapy or a TKI or 5 half-lives for a TKI (whichever is shorter), 21 days and progression by CT for immunotherapy, 21 days for RT, 21 days for surgery, or 28 days for an investigational agent.

  • Patients with ES-SCLC must have been treated with first-line therapy of platinum doublet + anti-PD(L)1 therapy, if eligible.
  • Patients with NSCLC without a driver mutation must have been treated with first-line therapy of platinum doublet + 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 subsequent platinum doublet therapy, if eligible.

• At least 18 years of age.

• ECOG performance status ≤ 1.

• Normal 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
  • AST(SGOT)/ALT(SGPT) ≤ 3 x IULN (or ≤ 5 x IULN if liver metastases are present)
  • Creatinine clearance > 60 mL/min by MDRD or by 24 hour urine
  • Serum uric acid ≤ 8 mg/dL (with or without medication control)

• The effects of ADI-PEG 20 on the developing human fetus are unknown. For this reason and because chemotherapeutics are known to be teratogenic, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for one month after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for one month after completion of study treatment.

• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion criteria

• 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

• Currently receiving any other investigational agents.

• 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.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

• History of seizure disorder not related to underlying cancer.

• Grade 2 or higher neuropathy

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

• Patients with known active Hepatitis B or C or HIV.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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114 participants in 3 patient groups

Phase I: ADI-PEG + gemcitabine + docetaxel

Experimental group

Description:

* 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.

Treatment:

Drug: Gemcitabine

Drug: Docetaxel

Drug: ADI-PEG 20

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

Experimental group

Description:

* 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.

Treatment:

Drug: Gemcitabine

Drug: Docetaxel

Drug: ADI-PEG 20

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

Experimental group

Description:

* 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.

Treatment:

Drug: Gemcitabine

Drug: Docetaxel

Drug: ADI-PEG 20