Author of

• 20152

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  P1.03 - Chemotherapy/Targeted Therapy (ID 689)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Chemotherapy/Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22599

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    P1.03-044 - Exploratory Analysis of Lung Cancer Patients in a Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) plus Gemcitabine (ID 10174)

    09:30 - 09:30  |  Author(s): J. Balkissoon
    • Abstract

    Background:
    NC-6004 is a polymeric micelle exhibiting sustained release of cisplatin and selective distribution to tumors, reducing plasma C~max~ and increasing AUC. Preclinical data showed less neuro- and nephrotoxicity with greater anti-tumor activity versus cisplatin. A previous trial evaluated NC-6004 and gemcitabine defining a recommended phase 2 dose of 90 mg/m[2]. A Bayesian continual reassessment method (N-CRM) design evaluated escalating doses of NC-6004 in combination with gemcitabine at 1250 mg/m[2].
    
    Method:
    Patients with refractory solid tumors were enrolled at four US sites. NC-6004 was administered intravenously (IV) at 60-180 mg/m[2] over 1 hour on Day 1 with gemcitabine at 1250 mg/m[2] IV over 30 mins on Day 1 and Day 8 every 3 weeks. All patients were administered a hydration regimen. Escalation of NC-6004 began with a single patient run-in, escalating by 15 mg/m[2] until a dose limiting toxicity (DLT) occurred at 180 mg/m[2]. Cohorts of four patients were then enrolled at each dose predicted by the N-CRM design. The maximum tolerated dose (MTD) was defined as the dose with the greatest posterior probability of target toxicity < 25%.
    
    Result:
    Among 22 patients enrolled in Phase 1b, 11 patients (six male, five female) had lung cancer. Non-squamous non-small cell lung cancer (NSCLC) was the most common subtype in 8/11 (72%) followed by squamous NSCLC, SCLC and large cell neuroendocrine histology in 1/11 (9%) of each type. Patients received a mean of 1.7 (range, 1-5) prior lines of therapy with 82% receiving a prior platinum agent. Common Grade 3/4 hematologic adverse events (AEs) among all patients were leukopenia (27%), thrombocytopenia (27%), anemia (18%) and neutropenia (18%). All AEs/DLTs were manageable and resolved. Of the four lung cancer patients treated at the MTD (135 mg/m[2]), the mean number of cycles received was 6 (range, 2-17). The total cumulative doses were 120-2340 mg/m[2]. Of ten patients evaluable, partial response was observed in 2/10 and stable disease in 7/10. Tumor shrinkage was observed in 6/10.
    
    Conclusion:
    The nanoparticle formulation allowed greater cisplatin equivalent doses with no clinically significant neuro-, oto- or nephrotoxicity allowing patients to receive treatment for a longer duration. Activity was observed in heavily pretreated platinum exposed lung cancer patients with a majority of patients exhibiting tumor regression or stable disease. NC-6004 with gemcitabine demonstrated promising activity and tolerability in heavily pretreated lung cancer patients in this trial and warrants further investigation.