A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: PEGylated recombinant human hyaluronidase PH20; Docetaxel
Intervention MeSH terms: Docetaxel
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Intervention model description: The study was planned to include a Dose Escalation portion utilizing a standard 3 + 3 dose escalation design. Participants were enrolled sequentially into their assigned dose cohort. The Treatment Period consisted of 21-day treatment cycles with administration of PEGPH20 on Day 1 (doses tested were 1.6, 3.0, and 2.2 ug/kg) and docetaxel (standard dosing 75 mg/m^2 for all participants) on Day 2 of each cycle.
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Recurrent, previously treated, locally advanced or metastatic NSCLC (non small cell lung cancer)

Summary:

      A Phase 1b study for participants with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) to
      participate in 1 of 2 portions of this study. The first portion is Dose Escalation in which
      participants are tested with PEGPH20 at various doses (1.6, 3.0, 2.2 and 2.8
      micrograms/kilogram (ug/kg)) in addition to dosing with the standard dose of docetaxel (PDoc)
      of 75 milligrams/meter squared (mg/m^2) once every 21-day cycle. Based on observations on the
      safety and tolerability of study treatment from dose escalation cohorts dosed to date (1.6
      and 3.0 ug/kg of PEGPH20), two additional dose levels will be tested, 2.2 and 2.8 ug/kg. Up
      to 30 additional participants may be enrolled to test these dose levels. The second portion
      of Phase 1b is Cohort Expansion in which the recommended Phase 2 dose (RP2D) of PDoc
      identified in dose escalation is administered every 21 days to approximately 50 participants
      with high hyaluronan (HA-high) prospectively measured in their tumor tissue.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed, approved Informed Consent.

          -  Histologically confirmed and documented previously treated Stage IIIB/IV Non-Small
             Cell Lung Cancer (NSCLC), having failed 1 previous platinum chemo regimen for locally
             advanced or metastatic disease.

          -  Cohort Expansion: Available archival tumor tissue block or 5-10 unstained, consecutive
             core biopsy slides from one archival tumor block that meet specific tissue
             requirements.

          -  Cohort Expansion: Participants must be determined to be hyaluronidase (HA)-high based
             on tumor biopsy that meets the requirements noted in the previous inclusion criterion.

          -  Cohort Expansion: One or more tumors measurable on computed tomography/magnetic
             resonance imaging (CT/MRI) scan per Response Evaluation Criteria on Solid Tumors
             (RECIST) v 1.1 (Eisenhauer 2009; Appendix C).

          -  Participants may have failed a programmed cell death protein 1 (PD-1) or programmed
             death-ligand 1 (PD-L1) therapy for advanced disease.

          -  Participants that are known to be epidermal growth factor (EGFR)-activating mutation
             positive must have received an EGFR inhibitor.

          -  Participants known to be anaplastic lymphoma kinase (ALK)-fusion/rearrangement
             mutation positive must have received an ALK inhibitor.

          -  Most prior therapies and prior targeted therapy are allowed and these specific
             therapies are detailed in the protocol.

          -  Life expectancy - =/> 3 months, Eastern Cooperative Oncology Group status = 0 or 1.

          -  Negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study
             medication) if female participants is of childbearing potential (WOCBP).

          -  Men and women agreement to use effective contraceptive method. For WOCBP and for men,
             agreement to use an effective contraceptive method from the time of screening
             throughout the study until 1 month for WOCBP or 6 months for men after administration
             of the last dose of any study medication.

          -  Specific ranges/levels of Screening labs that are acceptable per protocol.

          -  Age >/= 18 years.

        Exclusion Criteria:

          -  Previous treatment with docetaxel.

          -  Failed more than 3 treatment regimens for locally advanced or metastatic NSCLC.

          -  New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within the
             past 12 months before screening, or pre-existing atrial fibrillation.

          -  History of cerebrovascular accident or transient ischemic attack.

          -  Pre-existing carotid artery disease.

          -  Previous history of pulmonary embolism or pulmonary embolism found on screening exam.

          -  No ongoing requirement for corticosteroids

          -  Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
             at time of screening.

          -  Known infection with HIV and active infection with hepatitis B or C.

          -  Known allergy to hyaluronidase or any constituents of docetaxel formulation.

          -  Current use (within 10 days of day 1) of megestrol acetate.

          -  Chronic concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
             clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
             telithromycin, and voriconazole).

          -  Women currently pregnant or breast feeding.

          -  Intolerance to dexamethasone, as determined by Investigator.

          -  History of another primary cancer within the last 3 years that required treatment,
             with the exception of non-melanoma skin cancer, early stage prostate cancer, or
             curatively treated cervical carcinoma in situ.

          -  Any other disease, metabolic dysfunction, physical exam finding, or clinical lab
             finding that leads to reasonable suspicion of disease that contraindicates the use of
             an investigational drug that might affect interpretation of results or render subject
             at high risk for treatment complications.

          -  In opinion of Investigator, make subject unsuitable for study.

          -  Hypersensitivity to the active substance or ingredients of PEGPH20 and docetaxel.

          -  Subject's inability to comply with study and follow-up procedures, as judged by the
             Investigator.