A Phase 1b Study of PEGylated Recombinant Human Hyaluroni... | NCT02346370

Status Module

Description Module

Label	Type	Description	Intervention Names
PEGPH20 + Docetaxel	Experimental	PEGylated recombinant human hyaluronidase PH20 (PEGPH20) (1.6, 3.0, or 2.2 micrograms per kilogram (ug/kg)) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered on Day 2 of each 21-day cycle.	Drug: PEGylated recombinant human hyaluronidase PH20 Drug: Docetaxel

Name	Type	Description	Arm Group Labels	Other Names
PEGylated recombinant human hyaluronidase PH20	Drug		PEGPH20 + Docetaxel	PEGPH20

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Dose Limiting Toxicities (DLTs)	DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment.	Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)
Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel	Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.	From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20		Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)

Secondary Outcomes

Measure	Description	Time Frame
Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel	Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated electrochemiluminescence (ECL) immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with tandem mass spectrometry assay (LS-MS/MS). The following blood draw schedule was used, PEGPH20: Cycle 1 Day 1 (C1D1) (predose, 15 minutes (min), 1, 2 to 4, and 24 hours (hr) postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).

Eligibility Module

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.

Facility	Status	City	State	ZIP	Country	Contacts
California Cancer Associates for Research and Excellence (cCare)		Encinitas	California	92024	United States

PubMed Identifier	Type	Citation	Retractions
33982408	Derived	Heineman T, Baumgart M, Nanavati C, Gabrail N, Van Wart SA, Mager DE, Maneval DC, Fathallah AM, Sekulovich RE. Safety and pharmacokinetics of docetaxel in combination with pegvorhyaluronidase alfa in patients with non-small cell lung cancer. Clin Transl Sci. 2021 Sep;14(5):1875-1885. doi: 10.1111/cts.13041. Epub 2021 Jul 30.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 micrograms/kilograms (ug/kg) PEGylated recombinant human hyaluronidase PH20 (PEGPH20) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 micrograms/kilograms (ug/kg) PEGylated recombinant human hyaluronidase PH20 (PEGPH20) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered as an IV-infusion on Day 2 of each 21-day cycle.
BG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
BG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0007 BG0014 BG0024 BG00315

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Dose Limiting Toxicities (DLTs)

DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment.

The DLT-Evaluable population included all participants who received a full dose of study treatment and completed the initial 21 days of the study after the first dose or who experienced a DLT within the initial 21 days after the first dose and discontinued from the study (if they received a full dose of study drug).

Posted

Number

DLTs

Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 micrograms/kilograms (ug/kg) PEGylated recombinant human hyaluronidase PH20 (PEGPH20) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Units	Counts
Participants	OG0007 OG0014 OG0024

Title

Denominators

Categories

Neutropenia

Title	Measurements
	OG0000 OG0011 OG0020

Gastroenteritis Escherichia coli

Primary

Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel

Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Safety population

Posted

Count of Participants

Participants

From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Primary

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20

The MTD and RP2D were not established due to early study discontinuation.

Posted

Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)

ID	Title	Description
OG000	PEGPH20 + Docetaxel	PEGPH20 (1.6, 3.0, or 2.2 ug/kg) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Units	Counts
Participants	OG0000

Secondary

Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel

Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated electrochemiluminescence (ECL) immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with tandem mass spectrometry assay (LS-MS/MS). The following blood draw schedule was used, PEGPH20: Cycle 1 Day 1 (C1D1) (predose, 15 minutes (min), 1, 2 to 4, and 24 hours (hr) postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).

Due to early discontinuation of the study, Cmax was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel

Blood samples were collected from all participants per protocol and analyzed for plasma PEGPH20 concentration using a validated ECL immunoassay. Plasma docetaxel concentrations were analyzed using a validated liquid chromatography with LS-MS/MS. The following blood draw schedule was used, PEGPH20: C1D1 (predose, 15 min, 1, 2 to 4, and 24 hr postdose), C2 and all subsequent Cycles (predose, 1 hr postdose). Docetaxel: C1D2 (30 min after the start of the 1-hr infusion, 30 min post completion of the infusion, 4 to 6 and 24 hr post infusion), C1D3 (24 hr post infusion), C2D2 and C3D2 (30 min after the start of the 1-hour infusion, 30 min post completion of the infusion).

Due to early discontinuation of the study, Cmin was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel

Due to early discontinuation of the study, Tmax was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel

Due to early discontinuation of the study, t1/2 was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel

Due to early discontinuation of the study, the AUC was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel

Due to early discontinuation of the study, Vd was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel

Due to early discontinuation of the study, CL was not assessed.

Posted

PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Objective Response Rate (ORR)

ORR = complete response + partial response (CR + PR)

Due to early discontinuation of the study, ORR was not assessed.

Posted

From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Disease Control Rate (DCR)

Due to early discontinuation of the study, DCR was not assessed.

Posted

From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Duration of Response (DoR)

Due to early discontinuation of the study, DoR was not assessed.

Posted

From date of first CR or PR until the date of first documentation of disease progression or date of death, assessed up to data cutoff date (30 Nov 2016)

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Secondary

Progression-free Survival (PFS)

Due to early discontinuation of the study, PFS was not assessed.

Posted

From date of treatment start until date of first documentation of progressive disease or death from any cause, assessed up to 1 year 9 months

ID	Title	Description
OG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.
OG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	1.6 micrograms/kilograms (ug/kg) PEGylated recombinant human hyaluronidase PH20 (PEGPH20) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered as an IV-infusion on Day 2 of each 21-day cycle.	1	7	3	7	7	7
EG001	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	3.0 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.	3	4	3	4	4	4
EG002	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	2.2 ug/kg PEGPH20 was administered on Day 1 of each 21-day cycle (every 3 weeks) as an IV-infusion over 10 minutes, approximately 1 mL/min (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 mg/m^2) was administered as an IV-infusion on Day 2 of each 21-day cycle.	1	4	1	4	4	4

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Diverticulitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Gastroenteritis Escherichia coli	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Pericardial effusion	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected7 at risk EG0013 affected4 at risk EG0024 affected4 at risk
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Local swelling	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected7 at risk EG0012 affected4 at risk EG0023 affected4 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected7 at risk EG0013 affected4 at risk EG0021 affected4 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0012 affected4 at risk EG0020 affected4 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected7 at risk EG0011 affected4 at risk EG0021 affected4 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected7 at risk EG0012 affected4 at risk EG0020 affected4 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0012 affected4 at risk EG0021 affected4 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0011 affected4 at risk EG0021 affected4 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0021 affected4 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0013 affected4 at risk EG0021 affected4 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0022 affected4 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected4 at risk EG0020 affected4 at risk
Candida infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected4 at risk EG0020 affected4 at risk
Insomnia	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected7 at risk EG0012 affected4 at risk EG0021 affected4 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0022 affected4 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected4 at risk EG0022 affected4 at risk
Cushingoid	Endocrine disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected4 at risk EG0021 affected4 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D012008	Recurrence

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes