Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer

• Sponsor: Halozyme Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01453153
• Collaborator: (none)
• Enrollment: 28
• Locations: 12
• Arms: 2
• Duration (Months): 44
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 1B: Open label (all patients receive PEGPH20+gemcitabine), dose escalation, safety and tolerability study to determine the safe dose of PEGPH20 to use in combination with gemcitabine in Stage IV previously untreated pancreatic cancer patients.

Phase 2: Randomized, double blind study to compare the effect of overall survival of gemcitabine plus PEGPH20 vs gemcitabine plus placebo in Stage IV previously untreated pancreatic cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Pancreatic Cancer	Drug: Gemcitabine; Drug: PEGPH20; Drug: Placebo	Phase 1/Phase 2

Detailed Description

PEGPH20 is a PEGylated version of human recombinant PH20 hyaluronidase that, in preclinical studies, has been shown to remove HA from the extracellular matrix surrounding tumor cells by depolymerizing this substrate. 87% of pancreatic ductal adenocarcinomas (PDA) overexpress HA. PDA tumor tissue may be especially sensitive to the HA-degradation properties of PEGPH20 and thus more responsive to the cytotoxic effects of a given dose of gemcitabine. Modifying the extracellular environment to increase the penetration and efficacy of anti-cancer agents represents a novel approach to treating pancreatic cancer and may provide important therapeutic outcomes in patients with Stage IV Previously Untreated Pancreatic Cancer.

This Phase 1B/2 study will assess safety, tolerability, treatment effect, and various PK/PD endpoints.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Multicenter, International, Randomized, Double Blind, Placebo-Controlled, Study of Gemcitabine Combined With PEGPH20 Compared to Gemcitabine Combined With Placebo in Patients With Stage IV Previously Untreated Pancreatic Cancer
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Gemcitabine Gemcitabine + Placebo	Drug: Gemcitabine; 1000 mg/m2 given IV one time a week (Cycle 1: 7 weeks on treatment, 1 week off treatment; Cycle 2+: 3 Weeks on treatment, 1 week off treatment); Other Names: Gemzar ; Drug: Placebo; (Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment).; Other Names: Saline
Experimental: PEGPH20 PEGPH20+Gemcitabine	Drug: Gemcitabine; 1000 mg/m2 given IV one time a week (Cycle 1: 7 weeks on treatment, 1 week off treatment; Cycle 2+: 3 Weeks on treatment, 1 week off treatment); Other Names: Gemzar ; Drug: PEGPH20; (Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment). Doses start at 1.0 mcg/kg and modified until recommended Phase 2 dose is determined. Treatment continues until occurrence of significant treatment-related toxicity, progressive disease, or discontinuation criteria are met; Other Names: PEGylated Recombinant Human Hyaluronidase

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Dose-limiting Toxicity (DLT) [first 4 weeks of Cycle 1]

   The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by measuring the number of participants with a DLT during the dose-escalation phase of the study. A DLT was defined as any treatment-emergent National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Version 4.0, Grade 3 or greater event occurring within the first 4 weeks of treatment that was considered related to PEGPH20. Any PEGPH20 treatment-related AE that resulted in a drug interruption or reduction might have been considered a DLT at the Investigator's or Sponsor's discretion. Hypersensitivity/infusion reactions related to PEGPH20 dosing were not considered DLTs.

2. Recommended Phase 2 Dose (RP2D) [first 4 weeks of Cycle 1]

   The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by determining the RP2D, the highest dose level at which no more than 1 of 6 evaluable participants experienced a DLT in the first 4 weeks of treatment (considered a safe dose). The RP2D was determined based on review of safety and pharmacokinetic (PK) data from participants enrolled during the dose-escalation phase of the study.

Secondary Outcome Measures

1. Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses [Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment.

2. Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks [Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.

3. Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses [Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Blood samples were collected for pharmacokinetic assessment.

4. Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks [Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.

5. Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses [Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Blood samples were collected for pharmacokinetic assessment.

6. Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks [Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.

7. Apparent Half-life (t1/2) Following Single PEGPH20 Doses [Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. t1/2 is expressed as harmonic mean and pseudo standard deviation.

8. t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks [Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. t1/2 is expressed as harmonic mean and pseudo standard deviation.

9. Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Measurable Plasma Concentration (AUC0-T) Following Single PEGPH20 Doses [Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

   Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule.

10. AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks [Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)]

    Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. AUC0-T was calculated by the linear trapezoidal rule.

11. Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration [Baseline; post-Baseline (average treatment duration of 94.6 days)]

    The pharmacodynamic activity of PEGPH20 was evaluated by measuring plasma concentrations of HA after PEGPH20 dosing. Peak HA concentrations are the highest concentrations measured after a single dose of PEGPH20. HA samples were collected in Cycle 1 at the following time points: 1) Week 1/Day 1 (first visit) and Week 4 (first visit): predose and 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing (24-hour sample optional for Week 4); 2) all other visits in Cycle 1: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given). HA samples were collected in Cycles 2+ at the following time points: Week 3 of each cycle pre-PEGPH20 dose and 1 to 2 hours post-PEGPH20 dose.

12. H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies [Screening; Cycle 1 Week 7]

    An H-score approach methodology was developed and used to analyze staining in the tumor pericellular regions and the stroma separately. The H-score calculation was the sum of the products of the percentage of positive staining areas and the staining intensity (0, 1, 2 or 3), and ranged from 0 to 300. For example: [90% * 1 (weak)] + [10% * 2 (moderate)] + [0% * 3 (strong)] = 110. A score of 0 represents the absence of expression, and an H-score of 300 represents maximum expression. A larger decrease in H-score correlated with a greater target engagement of PEGPH20. As HA is a secreted protein, the scoring was performed in the immediate areas surrounding tumor (pericellular areas) as well as in stroma.

13. Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity [Baseline; up to 32 weeks for each individual participant (end of Cycle 7)]

    PEGPH20's effect on the metabolic activities of the tumor was assessed as the percent change in SUVmax (a measure of total lesion metabolic activity) using fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Assessment was done for the entire cohort of participants, not per treatment group.

14. Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites [Baseline; 24 hours hours; end of Cycle 1 (Week 7)]

    Dynamic control enhanced-magnetic resonance imaging (DCE-MRI) provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Using a 2-compartment pharmacokinetic model, an estimate of tissue (tumor) perfusion can be obtained by determining the exchange rate constant (Ktrans) of contrast exchange. Ktrans is defined as the volume transfer constant between extravascular/extracellular space to plasma space and is a measure of blood flow, vascular permeability, or both. Mean Ktrans values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.

15. Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites [Baseline; 24 hours hours; end of Cycle 1 (Week 7)]

    DCE-MRI provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Ve is defined as the extravascular-extracellular volume fraction and is a measure of extracellular, extravascular space. Mean Ve values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.

16. Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 [up to approximately 2 years 4 months]

    Target lesions (TLs), complete response (CR): Disappearance of all TLs. Partial response (PR): >=30% decrease in the sum of diameters of TLs, referencing baseline sums. Progressive disease (PD): >= 20% increase in the sum of diameters of TLs, referencing the smallest sum (including baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of >=5 mm. (The appearance of >=1 new lesions is considered progression.) Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For nontarget lesions (NTLs), CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits. PD: Unequivocal progression of existing NTLs. (The appearance of >=1 new lesions is considered progression.)

17. Objective Response Rate [up to approximately 2 years 4 months]

    Objective Response Rate is defined as the number of participants with a complete response plus the number of participants with a partial response, per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.

18. Disease Control Rate [up to approximately 2 years 4 months]

    Disease Control Rate is defined as the sum of the number of participants with a complete response, the number of participants with a partial response, and the number of participants with stable disease per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. SD: Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.

19. Progression-free Survival (PFS) [from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)]

    PFS duration was defined as the time from the first dose of PEGPH20 until objective tumor progression or death. Per RECIST, Version 1.1, for the evaluation of target lesions, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. Note: the appearance of 1 or more new lesions is also considered progression. For the evaluation of nontarget lesions, progressive disease is defined as the unequivocal progression of existing nontarget lesions. Note: The appearance of 1 or more new lesions is also considered progression.

20. Overall Survival [from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)]

    Overall survival was defined as the time from the time of the first dose of PEGPH20 until death.

21. Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9) [up to the end of Cycle 10 (up to Week 44)]

    CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.

22. Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml [up to the end of Cycle 10 (up to Week 44)]

    CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.

23. Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders [up to the end of Cycle 10 (up to Week 44)]

    CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. Responders are defined as participants who had a complete response or partial response, and non-responders are defined as participants who had stable disease, progressive disease, or an unknown tumor response, per RECIST, Version 1.1.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Patients with histologically confirmed Stage IV adenocarcinoma of the pancrease previously untreated for metastatic disease

• One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria

• Life expectancy of at least 3 months

• Signed, written IRB/EC-approved informed consent

• A negative serum pregnancy test, if female

Key Exclusion Criteria:

• Known brain metastasis

• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months

• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy

• Known allergy to hyaluronidase

• Women currently pregnant or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72707
2	California Pacific Medical Center	San Francisco	California	United States	94120
3	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
4	UMDNJ - New Jersey Medical School	Newark	New Jersey	United States	07103
5	NSLIJ Health System, Monter Cancer Center	New Hyde Park	New York	United States	11040
6	Mount Sinai School of Medicine	New York	New York	United States	10029
7	SUNY Upstate Medical University	Syracuse	New York	United States	13210
8	Seattle Cancer Care Alliance	Seattle	Washington	United States	90108
9	Chelyabinsk Regional Clinical Oncology Center	Chelyabinsk		Russian Federation
10	Russian Oncological Research Center n.a. N.N. Blokhin	Moscow		Russian Federation
11	Medical Radiological Research Center	Obninsk		Russian Federation
12	Omsk Regional Budget Medical Institution	Omsk		Russian Federation

Sponsors and Collaborators

• Halozyme Therapeutics

Investigators

• Study Director: Joy H Zhu, MD, PhD, Halozyme Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Halozyme Therapeutics
• ClinicalTrials.gov Identifier: NCT01453153
• Other Study ID Numbers: Halo-109-201
• First Posted: Oct 17, 2011
• Last Update Posted: Nov 30, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Halozyme Therapeutics: pancreatic; Cancer; Stage IV; untreated
• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine

Study Results

Participant Flow

Pre-assignment Detail	This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20).

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Period Title: Overall Study
STARTED	4	4	20
COMPLETED	0	0	0
NOT COMPLETED	4	4	20

Baseline Characteristics

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg	Total
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Total of all reporting groups
Overall Participants	4	4	20	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.5 (8.06)	59.0 (8.72)	60.3 (13.50)	58.7 (12.48)
Sex: Female, Male (Count of Participants)
Female	2 50%	2 50%	10 50%	14 50%
Male	2 50%	2 50%	10 50%	14 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 25%	0 0%	2 10%	3 10.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	3 75%	4 100%	18 90%	25 89.3%
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 Participants With a Dose-limiting Toxicity (DLT)
Description	The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by measuring the number of participants with a DLT during the dose-escalation phase of the study. A DLT was defined as any treatment-emergent National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Version 4.0, Grade 3 or greater event occurring within the first 4 weeks of treatment that was considered related to PEGPH20. Any PEGPH20 treatment-related AE that resulted in a drug interruption or reduction might have been considered a DLT at the Investigator's or Sponsor's discretion. Hypersensitivity/infusion reactions related to PEGPH20 dosing were not considered DLTs.
Time Frame	first 4 weeks of Cycle 1

Outcome Measure Data

Analysis Population Description

The DLT Evaluable Population: all participants enrolled during the dose escalation portion of the study who received at least 6 of 8 planned doses of PEGPH20 and 3 of 4 doses of gemcitabine in the first 4 weeks or had a DLT in the first 4 weeks.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	6
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Recommended Phase 2 Dose (RP2D)
Description	The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by determining the RP2D, the highest dose level at which no more than 1 of 6 evaluable participants experienced a DLT in the first 4 weeks of treatment (considered a safe dose). The RP2D was determined based on review of safety and pharmacokinetic (PK) data from participants enrolled during the dose-escalation phase of the study.
Time Frame	first 4 weeks of Cycle 1

Outcome Measure Data

Analysis Population Description

The DLT Evaluable Population: all participants enrolled during the dose escalation portion of the study who received at least 6 of 8 planned doses of PEGPH20 and 3 of 4 doses of gemcitabine in the first 4 weeks or had a DLT in the first 4 weeks

Arm/Group Title	PEGPH20 Plus Gemcitabine
Arm/Group Description	Participants received PEGPH20 1.0, 1.6, and 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. Participants received dexamethasone 4 or 8 mg orally, via intramuscular injection, or via IV injection. Dexamethasone (4 to 8 mg) was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	14
Number [micrograms per kilogram (μg/kg)]	3.0

3. Secondary Outcome

Title	Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses
Description	Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment.
Time Frame	Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: all enrolled participants

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Mean (Standard Deviation) [units per milliliter]	0.604 (0.438)	1.54 (0.491)	3.18 (1.28)

4. Secondary Outcome

Title	Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Description	Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame	Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: all enrolled participants. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	12
Mean (Standard Deviation) [units per milliliter]	1.08 (0.0878)	2.40 (0.542)	3.98 (1.16)

5. Secondary Outcome

Title	Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses
Description	Blood samples were collected for pharmacokinetic assessment.
Time Frame	Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	20
Mean (Standard Deviation) [units per milliliter]	0.626 (0.0607)	0.651 (0.155)	0.864 (0.375)

6. Secondary Outcome

Title	Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Description	Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame	Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	12
Mean (Standard Deviation) [Units per milliliter]	0.572 (0.0781)	0.976 (0.568)	1.52 (0.767)

7. Secondary Outcome

Title	Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses
Description	Blood samples were collected for pharmacokinetic assessment.
Time Frame	Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	20
Median (Full Range) [hours]	0.250	0.250	0.420

8. Secondary Outcome

Title	Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Description	Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame	Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	12
Median (Full Range) [hours]	0.330	0.325	0.420

9. Secondary Outcome

Title	Apparent Half-life (t1/2) Following Single PEGPH20 Doses
Description	The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Time Frame	Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed. t1/2 values were not calculated for the 1.0 μg/kg dose because there were insufficient data points in the profiles due to low concentrations.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	0	2	18
Mean (Standard Deviation) [hours]	18.6 (0.255)	8.24 (8.03)

10. Secondary Outcome

Title	t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Description	The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Time Frame	Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	2	9
Mean (Standard Deviation) [hours]	5.60 (3.08)	19.5 (7.75)	10.7 (4.06)

11. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Measurable Plasma Concentration (AUC0-T) Following Single PEGPH20 Doses
Description	Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule.
Time Frame	Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Mean (Standard Deviation) [Units*hour/milliliter]	1.39 (1.57)	13.6 (11.8)	31.5 (18.0)

12. Secondary Outcome

Title	AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Description	Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. AUC0-T was calculated by the linear trapezoidal rule.
Time Frame	Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	4	12
Mean (Standard Deviation) [Units*hour/milliliter]	2.99 (0.607)	21.5 (11.9)	35.2 (23.5)

13. Secondary Outcome

Title	Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration
Description	The pharmacodynamic activity of PEGPH20 was evaluated by measuring plasma concentrations of HA after PEGPH20 dosing. Peak HA concentrations are the highest concentrations measured after a single dose of PEGPH20. HA samples were collected in Cycle 1 at the following time points: 1) Week 1/Day 1 (first visit) and Week 4 (first visit): predose and 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing (24-hour sample optional for Week 4); 2) all other visits in Cycle 1: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given). HA samples were collected in Cycles 2+ at the following time points: Week 3 of each cycle pre-PEGPH20 dose and 1 to 2 hours post-PEGPH20 dose.
Time Frame	Baseline; post-Baseline (average treatment duration of 94.6 days)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Baseline	123.7 (137.6)	982.3 (1370)	164.7 (139.6)
After PEGPH20 administration	7288 (10027)	27818 (25866)	128411 (126357)

14. Secondary Outcome

Title	H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies
Description	An H-score approach methodology was developed and used to analyze staining in the tumor pericellular regions and the stroma separately. The H-score calculation was the sum of the products of the percentage of positive staining areas and the staining intensity (0, 1, 2 or 3), and ranged from 0 to 300. For example: [90% * 1 (weak)] + [10% * 2 (moderate)] + [0% * 3 (strong)] = 110. A score of 0 represents the absence of expression, and an H-score of 300 represents maximum expression. A larger decrease in H-score correlated with a greater target engagement of PEGPH20. As HA is a secreted protein, the scoring was performed in the immediate areas surrounding tumor (pericellular areas) as well as in stroma.
Time Frame	Screening; Cycle 1 Week 7

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only 1 participant had a screening and post-treatment specimen that qualified for staining. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	0	0	1
Screening pericellular tumor H-score	40
Screening stromal H-score	260
Post-treatment pericellular tumor H-score	15
Post-treatment stromal tumor H-score	150

15. Secondary Outcome

Title	Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity
Description	PEGPH20's effect on the metabolic activities of the tumor was assessed as the percent change in SUVmax (a measure of total lesion metabolic activity) using fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame	Baseline; up to 32 weeks for each individual participant (end of Cycle 7)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0, 1.6, or 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	28
Cycle 1	-36.7 (19.2)
Cycle 3	-43.2 (12.4)
Cycle 5	-39.3 (20.6)
Cycle 7	-41.2 (61.0)

16. Secondary Outcome

Title	Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites
Description	Dynamic control enhanced-magnetic resonance imaging (DCE-MRI) provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Using a 2-compartment pharmacokinetic model, an estimate of tissue (tumor) perfusion can be obtained by determining the exchange rate constant (Ktrans) of contrast exchange. Ktrans is defined as the volume transfer constant between extravascular/extracellular space to plasma space and is a measure of blood flow, vascular permeability, or both. Mean Ktrans values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame	Baseline; 24 hours hours; end of Cycle 1 (Week 7)

Outcome Measure Data

Analysis Population Description

ITT Population. DCE-MRI scans were performed for 6 participants. Only participants with data available were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0, 1.6, or 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	6
Participant 1, Baseline	0.124 (NA)
Participant 1, 24 hours	0.383 (NA)
Participant 1, End of Cycle 1	NA (NA)
Participant 2, Baseline	0.430 (NA)
Participant 2, 24 hours	0.468 (NA)
Participant 2, End of Cycle 1	NA (NA)
Participant 3, Baseline	0.402 (NA)
Participant 3, 24 hours	0.331 (NA)
Participant 3, End of Cycle 1	NA (NA)
Participant 4, Baseline	0.564 (NA)
Participant 4, 24 hours	0.672 (NA)
Participant 4, End of Cycle 1	0.646 (NA)
Participant 5, Baseline	0.135 (NA)
Participant 5, 24 hours	0.197 (NA)
Participant 5, End of Cycle 1	0.133 (NA)
Participant 6, Baseline	0.249 (NA)
Participant 6, 24 hours	0.376 (NA)
Participant 6, End of Cycle 1	0.078 (NA)

17. Secondary Outcome

Title	Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites
Description	DCE-MRI provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Ve is defined as the extravascular-extracellular volume fraction and is a measure of extracellular, extravascular space. Mean Ve values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame	Baseline; 24 hours hours; end of Cycle 1 (Week 7)

Outcome Measure Data

Analysis Population Description

ITT Population. DCE-MRI scans were performed for 6 participants. Only participants with data available were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0, 1.6, or 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	6
Participant 1, Baseline	0.162 (NA)
Participant 1, 24 hours	0.327 (NA)
Participant 1, End of Cycle 1	NA (NA)
Participant 2, Baseline	0.671 (NA)
Participant 2, 24 hours	0.386 (NA)
Participant 2, End of Cycle 1	NA (NA)
Participant 3, Baseline	0.481 (NA)
Participant 3, 24 hours	0.389 (NA)
Participant 3, End of Cycle 1	NA (NA)
Participant 4, Baseline	0.458 (NA)
Participant 4, 24 hours	0.788 (NA)
Participant 4, End of Cycle 1	0.751 (NA)
Participant 5, Baseline	0.380 (NA)
Participant 5, 24 hours	0.395 (NA)
Participant 5, End of Cycle 1	0.550 (NA)
Participant 6, Baseline	0.355 (NA)
Participant 6, 24 hours	0.825 (NA)
Participant 6, End of Cycle 1	0.425 (NA)

18. Secondary Outcome

Title	Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
Description	Target lesions (TLs), complete response (CR): Disappearance of all TLs. Partial response (PR): >=30% decrease in the sum of diameters of TLs, referencing baseline sums. Progressive disease (PD): >= 20% increase in the sum of diameters of TLs, referencing the smallest sum (including baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of >=5 mm. (The appearance of >=1 new lesions is considered progression.) Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For nontarget lesions (NTLs), CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits. PD: Unequivocal progression of existing NTLs. (The appearance of >=1 new lesions is considered progression.)
Time Frame	up to approximately 2 years 4 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
CR	0 0%	0 0%	0 0%
PR	0 0%	2 50%	8 40%
SD	1 25%	2 50%	6 30%
PD	3 75%	0 0%	0 0%
Unknown	0 0%	0 0%	6 30%

19. Secondary Outcome

Title	Objective Response Rate
Description	Objective Response Rate is defined as the number of participants with a complete response plus the number of participants with a partial response, per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Time Frame	up to approximately 2 years 4 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Count of Participants [Participants]	0 0%	2 50%	8 40%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 1.0 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; 0 to 60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 1.6 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	50
	Confidence Interval	(2-Sided) 95%; 7 to 93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 3.0 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	40
	Confidence Interval	(2-Sided) 95%; 19 to 64
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Disease Control Rate
Description	Disease Control Rate is defined as the sum of the number of participants with a complete response, the number of participants with a partial response, and the number of participants with stable disease per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. SD: Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Time Frame	up to approximately 2 years 4 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Count of Participants [Participants]	1 25%	4 100%	14 70%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 1.0 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	25
	Confidence Interval	(2-Sided) 95%; 1 to 81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 1.6 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 40 to 100
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PEGPH20 3.0 μg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	70
	Confidence Interval	(2-Sided) 95%; 46 to 88
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS duration was defined as the time from the first dose of PEGPH20 until objective tumor progression or death. Per RECIST, Version 1.1, for the evaluation of target lesions, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. Note: the appearance of 1 or more new lesions is also considered progression. For the evaluation of nontarget lesions, progressive disease is defined as the unequivocal progression of existing nontarget lesions. Note: The appearance of 1 or more new lesions is also considered progression.
Time Frame	from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Median (95% Confidence Interval) [days]	47.0	276.0	113.0

22. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from the time of the first dose of PEGPH20 until death.
Time Frame	from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Median (95% Confidence Interval) [days]	109.5	199.5	220.0

23. Secondary Outcome

Title	Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9)
Description	CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Time Frame	up to the end of Cycle 10 (up to Week 44)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	4	4	20
Cycle 1, Week 4, Visit 1	12897.5 (22345.65)	-7833.9 (13567.21)	-11800.3 (38780.49)
Cycle 1, Week 8, Visit 1	0.0 (NA)	-1.9 (2.69)	-15464.1 (41440.85)
Cycle 2, Week 4, Visit 1	0.0 (NA)	-1.2 (1.63)	-16581.0 (50738.98)
Cycle 3, Week 4, Visit 1	0.0 (NA)	-12628.0 (72538.77)
Cycle 4, Week 4, Visit 1	0.0 (NA)	-24089.1 (54120.73)
Cycle 5, Week 4, Visit 1	0.0 (NA)	-27214.3 (64893.40)
Cycle 6, Week 4, Visit 1	0.0 (NA)	-53200.6 (88132.74)
Cycle 7, Week 4, Visit 1	0.0 (NA)	-154964 (NA)
Cycle 8, Week 4, Visit 1	0.0 (NA)	-154946 (NA)
Cycle 9, Week 4, Visit 1	-154940 (NA)
Cycle 10, Week 4, Visit 1	-154937 (NA)

24. Secondary Outcome

Title	Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml
Description	CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Time Frame	up to the end of Cycle 10 (up to Week 44)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	PEGPH20 1.0 μg/kg	PEGPH20 1.6 μg/kg	PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	3	2	17
Cycle 1, Week 4, Visit 1	19346.2 (27370.41)	-23500.0 (NA)	-15018.9 (43611.09)
Cycle 1, Week 8, Visit 1	-18274.5 (44769.87)
Cycle 2, Week 4, Visit 1	-20724.4 (56673.61)
Cycle 3, Week 4, Visit 1	-16835.7 (85332.54)
Cycle 4, Week 4, Visit 1	-27530.1 (57504.01)
Cycle 5, Week 4, Visit 1	-32656.8 (71005.52)
Cycle 6, Week 4, Visit 1	-79800.9 (106251.1)
Cycle 7, Week 4, Visit 1	-154964 (NA)
Cycle 8, Week 4, Visit 1	-154946 (NA)
Cycle 9, Week 4, Visit 1	-154940 (NA)
Cycle 10, Week 4, Visit 1	-154937 (NA)

25. Secondary Outcome

Title	Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders
Description	CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. Responders are defined as participants who had a complete response or partial response, and non-responders are defined as participants who had stable disease, progressive disease, or an unknown tumor response, per RECIST, Version 1.1.
Time Frame	up to the end of Cycle 10 (up to Week 44)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.

Arm/Group Title	Responders	Non-responders
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.	Participants received PEGPH20 1.0, 1.6, or 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Measure Participants	10	18
Cycle 1, Week 4, Visit 1	-15677.1 (45962.74)	675.7 (15184.14)
Cycle 1, Week 8, Visit 1	-16367.0 (47164.85)	-6227.9 (12527.76)
Cycle 2, Week 4, Visit 1	-21587.2 (53784.34)	1377.1 (21979.93)
Cycle 3, Week 4, Visit 1	-28752.7 (61783.48)	23830.5 (78609.44)
Cycle 4, Week 4, Visit 1	-19976.6 (54603.40)	-32900.0 (NA)
Cycle 5, Week 4, Visit 1	-22347.6 (65803.24)	-29200.0 (NA)
Cycle 6, Week 4, Visit 1	-39900.5 (76719.16)
Cycle 7, Week 4, Visit 1	-77482.1 (109576.2)
Cycle 8, Week 4, Visit 1	-77472.8 (109563.0)
Cycle 9, Week 4, Visit 1	-154940 (NA)
Cycle 10, Week 4, Visit 1	-154937 (NA)

Adverse Events

Adverse Event Reporting Description	This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title	PEGPH20 1.0 μg/kg		PEGPH20 1.6 μg/kg		PEGPH20 3.0 μg/kg
Arm/Group Description	Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.		Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.		Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
All Cause Mortality
	PEGPH20 1.0 μg/kg		PEGPH20 1.6 μg/kg		PEGPH20 3.0 μg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		4/4 (100%)		17/20 (85%)
Serious Adverse Events
	PEGPH20 1.0 μg/kg		PEGPH20 1.6 μg/kg		PEGPH20 3.0 μg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		1/4 (25%)		13/20 (65%)
Blood and lymphatic system disorders
Thrombocytopenia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Cardiac disorders
Atrial fibrillation	0/4 (0%)		1/4 (25%)		0/20 (0%)
Gastrointestinal disorders
Abdominal pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Abdominal pain upper	0/4 (0%)		0/4 (0%)		1/20 (5%)
Duodenal obstruction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Pancreatitis	0/4 (0%)		0/4 (0%)		1/20 (5%)
General disorders
Disease progression	0/4 (0%)		0/4 (0%)		2/20 (10%)
Oedema peripheral	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hepatobiliary disorders
Bile duct obstruction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hepatic failure	0/4 (0%)		0/4 (0%)		1/20 (5%)
Infections and infestations
Pneumonia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Infusion related reaction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Investigations
Blood bilirubin increased	0/4 (0%)		0/4 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Hyperglycaemia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hypoalbuminaemia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Nervous system disorders
Cerebrovascular accident	1/4 (25%)		0/4 (0%)		1/20 (5%)
Psychiatric disorders
Mental status changes	0/4 (0%)		0/4 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Pulmonary embolism	1/4 (25%)		0/4 (0%)		1/20 (5%)
Vascular disorders
Hypotension	0/4 (0%)		0/4 (0%)		1/20 (5%)
Other (Not Including Serious) Adverse Events
	PEGPH20 1.0 μg/kg		PEGPH20 1.6 μg/kg		PEGPH20 3.0 μg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		4/4 (100%)		19/20 (95%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)		1/4 (25%)		8/20 (40%)
Leukopenia	0/4 (0%)		1/4 (25%)		2/20 (10%)
Lymphopenia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Neutropenia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Splenic infarction	1/4 (25%)		0/4 (0%)		0/20 (0%)
Thrombocytopenia	3/4 (75%)		1/4 (25%)		9/20 (45%)
Thrombocytosis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Cardiac disorders
Bradycardia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Pericarditis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Sinus tachycardia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Tachycardia	1/4 (25%)		1/4 (25%)		2/20 (10%)
Arrhythmia	0/4 (0%)		1/4 (25%)		0/20 (0%)
Ear and labyrinth disorders
Ear discomfort	1/4 (25%)		0/4 (0%)		0/20 (0%)
Tinnitus	0/4 (0%)		0/4 (0%)		1/20 (5%)
Vertigo	0/4 (0%)		0/4 (0%)		1/20 (5%)
Eye disorders
Diplopia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Eyelid pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Vision blurred	1/4 (25%)		0/4 (0%)		3/20 (15%)
Gastrointestinal disorders
Abdominal distension	2/4 (50%)		0/4 (0%)		1/20 (5%)
Abdominal pain	1/4 (25%)		0/4 (0%)		1/20 (5%)
Abdominal pain lower	0/4 (0%)		0/4 (0%)		1/20 (5%)
Abdominal pain upper	2/4 (50%)		1/4 (25%)		3/20 (15%)
Abdominal tenderness	0/4 (0%)		0/4 (0%)		1/20 (5%)
Ascites	0/4 (0%)		2/4 (50%)		0/20 (0%)
Constipation	0/4 (0%)		0/4 (0%)		2/20 (10%)
Diarrhoea	0/4 (0%)		1/4 (25%)		6/20 (30%)
Dry mouth	1/4 (25%)		0/4 (0%)		2/20 (10%)
Dyspepsia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Dysphagia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Epigastric discomfort	0/4 (0%)		1/4 (25%)		0/20 (0%)
Eructation	0/4 (0%)		0/4 (0%)		2/20 (10%)
Flatulence	0/4 (0%)		0/4 (0%)		1/20 (5%)
Gastritis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Gastrointestinal sounds abnormal	0/4 (0%)		0/4 (0%)		1/20 (5%)
Lip oedema	0/4 (0%)		0/4 (0%)		1/20 (5%)
Lip pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Mouth ulceration	0/4 (0%)		1/4 (25%)		1/20 (5%)
Nausea	2/4 (50%)		0/4 (0%)		8/20 (40%)
Oral pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Rectal haemorrhage	0/4 (0%)		0/4 (0%)		1/20 (5%)
Retching	0/4 (0%)		0/4 (0%)		1/20 (5%)
Sensitivity of teeth	0/4 (0%)		0/4 (0%)		1/20 (5%)
Stomatitis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Tongue discolouration	0/4 (0%)		0/4 (0%)		1/20 (5%)
Vomiting	2/4 (50%)		0/4 (0%)		5/20 (25%)
General disorders
Application site rash	0/4 (0%)		0/4 (0%)		1/20 (5%)
Asthenia	1/4 (25%)		0/4 (0%)		6/20 (30%)
Catheter site erythema	0/4 (0%)		0/4 (0%)		1/20 (5%)
Chest discomfort	1/4 (25%)		0/4 (0%)		1/20 (5%)
Chills	0/4 (0%)		1/4 (25%)		0/20 (0%)
Early satiety	0/4 (0%)		0/4 (0%)		1/20 (5%)
Fatigue	2/4 (50%)		1/4 (25%)		11/20 (55%)
Injection site extravasation	0/4 (0%)		0/4 (0%)		1/20 (5%)
Malaise	0/4 (0%)		0/4 (0%)		1/20 (5%)
Mucosal inflammation	0/4 (0%)		0/4 (0%)		1/20 (5%)
Oedema peripheral	3/4 (75%)		2/4 (50%)		11/20 (55%)
Pyrexia	2/4 (50%)		2/4 (50%)		1/20 (5%)
Thirst	1/4 (25%)		0/4 (0%)		0/20 (0%)
Hepatobiliary disorders
Bile duct stenosis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hyperbilirubinaemia	0/4 (0%)		1/4 (25%)		2/20 (10%)
Infections and infestations
Candidiasis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Fungal infection	0/4 (0%)		0/4 (0%)		1/20 (5%)
Oral candidiasis	1/4 (25%)		0/4 (0%)		1/20 (5%)
Pneumonia	1/4 (25%)		0/4 (0%)		0/20 (0%)
Upper respiratory tract infection	0/4 (0%)		1/4 (25%)		0/20 (0%)
Injury, poisoning and procedural complications
Contrast media reaction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Excoriation	0/4 (0%)		0/4 (0%)		1/20 (5%)
Fall	1/4 (25%)		0/4 (0%)		2/20 (10%)
Infusion related reaction	1/4 (25%)		0/4 (0%)		0/20 (0%)
Procedural pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Spinal compression fracture	0/4 (0%)		0/4 (0%)		1/20 (5%)
Investigations
Alanine aminotransferase increased	0/4 (0%)		1/4 (25%)		2/20 (10%)
Aspartate aminotransferase increased	0/4 (0%)		1/4 (25%)		2/20 (10%)
Blood alkaline phosphatase increased	0/4 (0%)		0/4 (0%)		2/20 (10%)
Blood bilirubin increased	0/4 (0%)		1/4 (25%)		1/20 (5%)
Eastern Cooperative Oncology Group performance status worsened	1/4 (25%)		0/4 (0%)		0/20 (0%)
Neutrophil count decreased	0/4 (0%)		0/4 (0%)		2/20 (10%)
Respiratory rate increased	0/4 (0%)		0/4 (0%)		1/20 (5%)
Weight decreased	1/4 (25%)		0/4 (0%)		2/20 (10%)
Weight increased	0/4 (0%)		0/4 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Decreased appetite	0/4 (0%)		1/4 (25%)		8/20 (40%)
Dehydration	1/4 (25%)		0/4 (0%)		2/20 (10%)
Fluid retention	0/4 (0%)		0/4 (0%)		1/20 (5%)
Glucose tolerance impaired	0/4 (0%)		1/4 (25%)		0/20 (0%)
Hyperglycaemia	1/4 (25%)		1/4 (25%)		0/20 (0%)
Hypoalbuminaemia	1/4 (25%)		0/4 (0%)		4/20 (20%)
Hypocalcaemia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hypoglycaemia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hypokalaemia	1/4 (25%)		1/4 (25%)		3/20 (15%)
Hypomagnesaemia	0/4 (0%)		1/4 (25%)		2/20 (10%)
Hyponatraemia	0/4 (0%)		0/4 (0%)		3/20 (15%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		1/4 (25%)		6/20 (30%)
Back pain	1/4 (25%)		1/4 (25%)		2/20 (10%)
Bone pain	0/4 (0%)		1/4 (25%)		0/20 (0%)
Intervertebral disc degeneration	1/4 (25%)		0/4 (0%)		0/20 (0%)
Muscle atrophy	2/4 (50%)		0/4 (0%)		0/20 (0%)
Muscle spasms	3/4 (75%)		0/4 (0%)		12/20 (60%)
Muscular weakness	1/4 (25%)		0/4 (0%)		1/20 (5%)
Musculoskeletal discomfort	0/4 (0%)		0/4 (0%)		1/20 (5%)
Musculoskeletal pain	1/4 (25%)		0/4 (0%)		2/20 (10%)
Myalgia	2/4 (50%)		0/4 (0%)		10/20 (50%)
Pain in extremity	2/4 (50%)		0/4 (0%)		4/20 (20%)
Pain in jaw	0/4 (0%)		0/4 (0%)		1/20 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/4 (0%)		0/4 (0%)		1/20 (5%)
Nervous system disorders
Basal ganglia infarction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Cognitive disorder	0/4 (0%)		0/4 (0%)		1/20 (5%)
Dizziness	0/4 (0%)		1/4 (25%)		3/20 (15%)
Dysgeusia	3/4 (75%)		0/4 (0%)		2/20 (10%)
Headache	1/4 (25%)		0/4 (0%)		1/20 (5%)
Hypoaesthesia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Neuropathy peripheral	0/4 (0%)		0/4 (0%)		1/20 (5%)
Presyncope	0/4 (0%)		0/4 (0%)		1/20 (5%)
Syncope	0/4 (0%)		1/4 (25%)		0/20 (0%)
Tremor	0/4 (0%)		0/4 (0%)		1/20 (5%)
Psychiatric disorders
Anger	0/4 (0%)		0/4 (0%)		1/20 (5%)
Anxiety	0/4 (0%)		0/4 (0%)		2/20 (10%)
Depression	0/4 (0%)		0/4 (0%)		3/20 (15%)
Insomnia	1/4 (25%)		1/4 (25%)		5/20 (25%)
Mental status changes	1/4 (25%)		1/4 (25%)		0/20 (0%)
Renal and urinary disorders
Renal failure acute	0/4 (0%)		0/4 (0%)		1/20 (5%)
Urinary hesitation	0/4 (0%)		0/4 (0%)		1/20 (5%)
Urinary incontinence	0/4 (0%)		0/4 (0%)		1/20 (5%)
Reproductive system and breast disorders
Erectile dysfunction	0/4 (0%)		0/4 (0%)		1/20 (5%)
Penile oedema	0/4 (0%)		1/4 (25%)		0/20 (0%)
Scrotal oedema	0/4 (0%)		0/4 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/4 (25%)		0/4 (0%)		0/20 (0%)
Cough	0/4 (0%)		1/4 (25%)		0/20 (0%)
Dysphonia	0/4 (0%)		0/4 (0%)		3/20 (15%)
Dyspnoea	1/4 (25%)		0/4 (0%)		3/20 (15%)
Dyspnoea exertional	0/4 (0%)		0/4 (0%)		2/20 (10%)
Epistaxis	0/4 (0%)		1/4 (25%)		1/20 (5%)
Hiccups	1/4 (25%)		0/4 (0%)		1/20 (5%)
Oropharyngeal pain	0/4 (0%)		1/4 (25%)		0/20 (0%)
Pleural effusion	0/4 (0%)		0/4 (0%)		1/20 (5%)
Productive cough	0/4 (0%)		0/4 (0%)		3/20 (15%)
Pulmonary embolism	0/4 (0%)		0/4 (0%)		3/20 (15%)
Sinus congestion	0/4 (0%)		0/4 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
Alopecia	0/4 (0%)		0/4 (0%)		1/20 (5%)
Decubitus ulcer	1/4 (25%)		0/4 (0%)		0/20 (0%)
Erythema	0/4 (0%)		0/4 (0%)		1/20 (5%)
Hyperhidrosis	0/4 (0%)		0/4 (0%)		1/20 (5%)
Night sweats	1/4 (25%)		0/4 (0%)		2/20 (10%)
Petechiae	0/4 (0%)		0/4 (0%)		1/20 (5%)
Pruritus	0/4 (0%)		0/4 (0%)		1/20 (5%)
Rash maculo-papular	0/4 (0%)		0/4 (0%)		1/20 (5%)
Rash pruritic	1/4 (25%)		0/4 (0%)		1/20 (5%)
Skin ulcer	0/4 (0%)		0/4 (0%)		1/20 (5%)
Vascular disorders
Deep vein thrombosis	2/4 (50%)		0/4 (0%)		0/20 (0%)
Flushing	0/4 (0%)		0/4 (0%)		2/20 (10%)
Hypertension	0/4 (0%)		1/4 (25%)		1/20 (5%)
Hypotension	0/4 (0%)		0/4 (0%)		3/20 (15%)
Jugular vein thrombosis	1/4 (25%)		0/4 (0%)		0/20 (0%)
Lymphoedema	0/4 (0%)		0/4 (0%)		1/20 (5%)
Venous thrombosis	1/4 (25%)		0/4 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. The Investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless written permission from the sponsor (Halozyme) is obtained.