PRIMAL: A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC

• Sponsor: Halozyme Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02346370
• Collaborator: (none)
• Enrollment: 16
• Locations: 8
• Arm: 1
• Actual Duration (Months): 21.1
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: PEGylated recombinant human hyaluronidase PH20; Drug: Docetaxel	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• 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.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)
• Primary Purpose: Treatment
• Official Title: PRIMAL STUDY: A Phase 1b, Open-label, Multicenter, Multinational Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel (PDoc) in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: Feb 10, 2015
• Actual Primary Completion Date: Aug 9, 2016
• Actual Study Completion Date: Nov 14, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PEGPH20 + Docetaxel 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; Other Names: PEGPH20 ; Drug: Docetaxel; Other Names: Taxotere

Outcome Measures

Primary Outcome Measures

1. Number of Dose Limiting Toxicities (DLTs) [Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)]

   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.

2. Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel [From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months]

   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.

3. Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20 [Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)]

Secondary Outcome Measures

1. Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

2. Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

3. Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

4. Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

5. Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

6. Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

7. Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel [PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2]

   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).

8. Objective Response Rate (ORR) [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]

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

9. Disease Control Rate (DCR) [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]

10. Duration of Response (DoR) [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)]

11. Progression-free Survival (PFS) [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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Cancer Associates for Research and Excellence (cCare)	Encinitas	California	United States	92024
2	California Cancer Associates for Research and Excellence (cCare)	Fresno	California	United States	93720
3	Moores UCSD Cancer Center, Clinical Trials Office	San Diego	California	United States	92093
4	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
5	University of Rochester	Rochester	New York	United States	14642
6	Levine Cancer Institute	Charlotte	North Carolina	United States	28112
7	Gabrail Cancer Center Research	Canton	Ohio	United States	44718-2566
8	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Halozyme Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Halozyme Therapeutics
• ClinicalTrials.gov Identifier: NCT02346370
• Other Study ID Numbers: HALO-107-201
• First Posted: Jan 27, 2015
• Last Update Posted: Feb 8, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Halozyme Therapeutics: Recurrent, previously treated, locally advanced or metastatic NSCLC (non small cell lung cancer)
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel

Study Results

Participant Flow

Pre-assignment Detail	A total of 16 participants were enrolled, of whom 1 participant was not treated due to disease progression prior to treatment and 15 participants received study treatment.

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	8	4	4
COMPLETED	0	0	0
NOT COMPLETED	8	4	4

Baseline Characteristics

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	7	4	4	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (8.90)	57.8 (10.53)	65.5 (8.10)	62.6 (9.03)
Sex: Female, Male (Count of Participants)
Female	6 85.7%	2 50%	2 50%	10 66.7%
Male	1 14.3%	2 50%	2 50%	5 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 25%	0 0%	1 6.7%
Not Hispanic or Latino	7 100%	3 75%	4 100%	14 93.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 25%	1 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	1 25%	0 0%	1 6.7%
Black or African American	1 14.3%	1 25%	0 0%	2 13.3%
White	6 85.7%	2 50%	3 75%	11 73.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Dose Limiting Toxicities (DLTs)
Description	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.
Time Frame	Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	7	4	4
Neutropenia	0	1	0
Gastroenteritis Escherichia coli	0	1	0
Sepsis	0	1	0
Deep vein thrombosis	0	1	1

2. Primary Outcome

Title	Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel
Description	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.
Time Frame	From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	7	4	4
AEs greater than or equal to grade 3	5 71.4%	4 100%	3 75%
PEGPH20-related AEs	6 85.7%	4 100%	4 100%
Docetaxel-related AEs	7 100%	4 100%	4 100%
AEs with outcome of death	0 0%	0 0%	0 0%
SAEs	3 42.9%	3 75%	1 25%
Treatment-related SAEs	1 14.3%	2 50%	1 25%
AEs leading to discontinuation of study drug	1 14.3%	1 25%	2 50%

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20
Time Frame	Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PEGPH20 + Docetaxel
Arm/Group Description	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.
Measure Participants	0

4. Secondary Outcome

Title	Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

6. Secondary Outcome

Title	Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

8. Secondary Outcome

Title	Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

10. Secondary Outcome

Title	Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel
Description	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).
Time Frame	PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR = complete response + partial response (CR + PR)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

12. Secondary Outcome

Title	Disease Control Rate (DCR)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

13. Secondary Outcome

Title	Duration of Response (DoR)
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

14. Secondary Outcome

Title	Progression-free Survival (PFS)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel	Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel	Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

Adverse Events

Time Frame	From date of first dose until 30 days after the last dose of study drug, up to approximately 1 year 10 months.
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs) and serious adverse events were reported. Adverse event severity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. The Safety Population was evaluated and included all participants who received at least one dose of study treatment.
Arm/Group Title	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel		Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel		Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel		Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel		Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		3/4 (75%)		1/4 (25%)
Serious Adverse Events
	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel		Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel		Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)		3/4 (75%)		1/4 (25%)
Blood and lymphatic system disorders
Neutropenia	0/7 (0%)		1/4 (25%)		0/4 (0%)
Cardiac disorders
Pericardial effusion	0/7 (0%)		0/4 (0%)		1/4 (25%)
Infections and infestations
Pneumonia	1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Diverticulitis	0/7 (0%)		1/4 (25%)		0/4 (0%)
Gastroenteritis Escherichia coli	0/7 (0%)		1/4 (25%)		0/4 (0%)
Sepsis	0/7 (0%)		1/4 (25%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/7 (14.3%)		0/4 (0%)		0/4 (0%)
Pneumothorax	0/7 (0%)		1/4 (25%)		0/4 (0%)
Vascular disorders
Deep vein thrombosis	0/7 (0%)		1/4 (25%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel		Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel		Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		4/4 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Neutropenia	1/7 (14.3%)		3/4 (75%)		1/4 (25%)
Thrombocytopenia	1/7 (14.3%)		1/4 (25%)		0/4 (0%)
Endocrine disorders
Cushingoid	1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Gastrointestinal disorders
Nausea	3/7 (42.9%)		2/4 (50%)		0/4 (0%)
Diarrhoea	1/7 (14.3%)		2/4 (50%)		1/4 (25%)
Vomiting	2/7 (28.6%)		1/4 (25%)		1/4 (25%)
Constipation	2/7 (28.6%)		0/4 (0%)		1/4 (25%)
Abdominal pain	0/7 (0%)		1/4 (25%)		1/4 (25%)
Gastroesophageal reflux disease	2/7 (28.6%)		0/4 (0%)		0/4 (0%)
General disorders
Fatigue	6/7 (85.7%)		3/4 (75%)		4/4 (100%)
Oedema peripheral	3/7 (42.9%)		0/4 (0%)		1/4 (25%)
Pyrexia	4/7 (57.1%)		0/4 (0%)		0/4 (0%)
Local swelling	1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Infections and infestations
Candida infection	1/7 (14.3%)		1/4 (25%)		0/4 (0%)
Sepsis	1/7 (14.3%)		1/4 (25%)		0/4 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/7 (14.3%)		0/4 (0%)		2/4 (50%)
Musculoskeletal and connective tissue disorders
Muscle spasms	4/7 (57.1%)		2/4 (50%)		3/4 (75%)
Myalgia	4/7 (57.1%)		3/4 (75%)		1/4 (25%)
Bone pain	1/7 (14.3%)		2/4 (50%)		0/4 (0%)
Arthralgia	2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Headache	2/7 (28.6%)		0/4 (0%)		1/4 (25%)
Neuropathy Peripheral	1/7 (14.3%)		0/4 (0%)		2/4 (50%)
Peripheral sensory neuropathy	1/7 (14.3%)		1/4 (25%)		0/4 (0%)
Psychiatric disorders
Insomnia	3/7 (42.9%)		2/4 (50%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	4/7 (57.1%)		1/4 (25%)		0/4 (0%)
Dyspnoea	3/7 (42.9%)		1/4 (25%)		1/4 (25%)
Oropharyngeal pain	3/7 (42.9%)		0/4 (0%)		1/4 (25%)
Dysphonia	1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Productive cough	1/7 (14.3%)		0/4 (0%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Alopecia	2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Onycholysis	2/7 (28.6%)		0/4 (0%)		0/4 (0%)
Vascular disorders
Deep vein thrombosis	0/7 (0%)		1/4 (25%)		2/4 (50%)

Limitations/Caveats

This study was discontinued early by the Sponsor during the Dose Escalation Period.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.