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