Trial of NanoPac Intratumoral Injection in Lung Cancer

NanoPac is very small (submicron) particles of the chemotherapy drug, paclitaxel, which is administered intravenously in a number of types of cancer. These submicron particles are injected directly into solid tumors to target cancer at the site of disease with less systemic exposure than intravenously administered chemotherapy. In this study, the submicron particle paclitaxel will be injected directly into tumors in the lungs of people with small cell or non-small cell lung cancer. All subjects in this study will receive NanoPac and will be evaluated to see if NanoPac is safe and has an effect on the tumor within the lung.

• NanoPac (sterile nanoparticulate paclitaxel) Powder for Suspension (Drug), also known as paclitaxel: NanoPac is manufactured using a Precipitation with Compressed Antisolvent (PCA) technique that employs supercritical carbon dioxide and acetone to generate paclitaxel nanoparticles within a well-characterized particle-size distribution. Following PCA, NanoPac is filled into a clear 60mL Type 1, USP, clear-glass vial (306 mg/vial) as a powder fill of nanoparticulate paclitaxel, closed with a bromobutyl rubber stopper and aluminum crimp seal, and sterilized by gamma irradiation. Prior to administration at the hospital/clinic, NanoPac will be reconstituted with 1% Polysorbate 80, NF in 0.9% Sodium Chloride for Injection, USP, to form a suspension. The suspension will be further diluted with 0.9% Sodium Chloride for Injection, USP to achieve the final clinical formulation.

Primary outcomes

• Number of Participants With Treatment Emergent Adverse Events [Day 1 to Week 24 (6 Months)]: AEs were collected at all study visits from the time of dosing. Subjects were required to spontaneously report any AE. Study personnel asked open-ended questions to obtain information about AEs at every visit.

Secondary outcomes

• Concentration of Paclitaxel in the Systemic Circulation Post-injection [Day 1, Weeks 1, 2, 4, 5, 6, 8, 9, 10, 12, 18, and 24]: To characterize the pharmacokinetics of intratumoral NanoPac, plasma samples were taken on days of NanoPac injection prior to injection and at 1, 2, and 4 hours after NanoPac injection, as well as at all other study visits up through Week 24. Plasma paclitaxel concentrations are reported in pg/mL.
• Progression Free Survival (PFS) [Weeks 24, 38, and 52]: Progression free survival (PFS) as assessed using RECIST v1.1
• Overall Survival [Weeks 24, 38, and 52]: Overall survival (OS) as determined by survival time following first NanoPac injection
• Change in Tumor Dimensions (Longest Diameter) [Weeks 12, 24, 38, and 52]: Change in longest dimension (cm) as determined by CT imaging compared to baseline (Screening)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Signed informed consent;
* Age ≥18 years and able to tolerate the EBUS-TBNI procedure;
* Histologically/cytologically confirmed lung cancer. Eligible subjects may include, for example: primary or recurrent non-resectable disease, locally advanced stages II and III with nodal disease, stage IV advanced disease;
* At least one lesion documented via imaging (within 4 weeks of Screening) which can be accessed using EBUS-TBNI;
* Subject is not a candidate for surgery;
* Has received or plans to receive SOC chemotherapy; adequate hematologic recovery must be confirmed according to the institution's SOC;
* Performance Status (ECOG) 0-2 at study entry;
* Life expectancy of at least 6 months;
* Adequate marrow, liver, and renal function at study entry;

  * ANC ≥ 1.5 x 109/L;
  * Hemoglobin ≥ 9.0 grams/dL;
  * Platelets ≥ 75 x 109/L;
  * Total bilirubin ≤ 1.5x institutional ULN;
  * AST/ ALT ≤ 2.5x institutional ULN;
  * Creatinine ≤ 1.5x institutional ULN;
* Appropriate steps taken to minimize or avoid the potential for pregnancy for subjects of child-bearing potential.*

Exclusion Criteria:

* Significant cardiac disease (Class III or IV per New York Heart Association guidelines);
* Active bacterial, viral, or fungal infections (including active AIDS, hepatitis B or hepatitis C);
* Symptomatic central nervous system (CNS) metastasis which are neurologically unstable, or CNS disease requiring increase in steroid dose (treated metastatic disease and stable steroid use are not excluded)
* Known hypersensitivity to study agent;
* Pregnant or breastfeeding women.

Participant flow

Outcome results

• Number of Participants With Treatment Emergent Adverse Events (Primary), Count of participants, Participants: NanoPac 15 mg/mL 18
• Concentration of Paclitaxel in the Systemic Circulation Post-injection (Secondary), Mean, pg/mL: NanoPac 15 mg/mL - One Injection 566.7 +/- 981.50; NanoPac 15 mg/mL - Two Injections 44.2 +/- 82.61; NanoPac 15 mg/mL - Three Injections 32.8 +/- 103.72
• Progression Free Survival (PFS) (Secondary), Count of participants, Participants: NanoPac 15 mg/mL - One Injection 0; NanoPac 15 mg/mL - Two Injections 0; NanoPac 15 mg/mL - Three Injections 5
• Overall Survival (Secondary), Count of participants, Participants: NanoPac 15 mg/mL - One Injection 0; NanoPac 15 mg/mL - Two Injections 3; NanoPac 15 mg/mL - Three Injections 6
• Change in Tumor Dimensions (Longest Diameter) (Secondary), Mean, cm: NanoPac 15 mg/mL - One Injection ; NanoPac 15 mg/mL - Two Injections 2.06 +/- 2.913; NanoPac 15 mg/mL - Three Injections -0.23 +/- 0.907

Adverse events

Time frame: All-Cause Mortality was assessed through study completion, up to 52 weeks; all adverse events were collected from the time of dosing until Week 24.

Serious adverse events by term

Other adverse events by term

49 more terms not shown.

• Study Protocol (PDF, 2021-07-07)
• Statistical Analysis Plan (PDF, 2023-11-13)

• Shelagh Verco, PhD, Study director, US Biotest, Inc.