Combination Therapy With NC-6004 and Gemcitabine in Advanced Solid Tumors or Non-Small Cell Lung, Biliary and Bladder Cancer

A Phase 1b/2 Dose Escalation and Expansion Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients With Advanced Solid Tumors or Non-Small Cell Lung, Biliary Tract, and Bladder Cancer

In the dose escalation phase (Part 1), this study will determine the dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and recommended Phase 2 (RPII) dose of NC 6004 in combination with gemcitabine.

In the expansion phase of the study (Part 2), study will evaluate the activity, safety, and tolerability at the RPII dose identified in Part 1 in patients with squamous NSCLC, biliary tract, and bladder cancer.

Inclusion Criteria:

• (Part 1 only) Have a histologically or cytologically confirmed diagnosis of advanced solid tumor that has relapsed or is refractory to standard curative or palliative therapy or has a contraindication to standard therapy.
• (Part 2 only) Cohort 1: Have histologically or cytologically confirmed diagnosis of Stage IV squamous NSCLC and have not received prior chemotherapy or immunotherapy for metastatic disease and are not known to be PD-L1 positive (known high PD-L1 expression defined as Tumor Proportion Score [TPS] greater than or equal to 50%). Patients with known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene must have received at least 1 and up to 2 targeted therapies prior to enrollment.
• (Part 2 only) Cohort 2: Have histologically or cytologically confirmed diagnosis of nonresectable, recurrent, or metastatic biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) and have not received prior systemic anticancer therapy for advanced or metastatic disease.
• (Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery.
• Have measurable disease per RECIST version 1.1.
• Have an ECOG PS of 0 to 1, with the exception of patients in Part 2 (Cohort 3, unfit bladder cancer patients) who may have an ECOG PS of 2
• Adequate bone marrow reserve, liver and renal function
• Have a negative pregnancy test result at Screening for females of childbearing potential
• Male patients must agree to use a condom during treatment and for 90 days after dosing and must agree not to donate sperm for 90 days after dosing
• Women of childbearing potential are willing to agree to use 1 of the study defined effective methods of birth control from the time of study entry to 6 months after the last day of treatment
• Reasonably recovered from preceding major surgery as judged by the investigator or no major surgery within 4 weeks prior to the start of Day 1 treatment

Exclusion Criteria:

• Have received prior platinum therapy in the past 3 months (Part 1) or 6 months in the adjuvant or neoadjuvant setting (Part 2).
• Have received prior cisplatin and gemcitabine concomitantly within the last 6 months or are refractory to cisplatin and gemcitabine.
• Unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment, including investigational treatment
• Have evidence suggesting pulmonary fibrosis or interstitial pneumonia.
• Have a history of thrombocytopenia with complications
• Have known hypersensitivity to platinum compounds or gemcitabine.
• Have uncontrolled diabetes or have hypertension requiring more than 3 medications for control of hypertension.
• Have pre-existing alcoholic liver injury or significant liver disease.
• Pregnant or breast feeding