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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gemcitabine | Active Comparator | Gemcitabine + Placebo |
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| PEGPH20 | Experimental | PEGPH20+Gemcitabine |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemcitabine | Drug | 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) |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Dose-limiting Toxicity (DLT) | 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. | first 4 weeks of Cycle 1 |
| Recommended Phase 2 Dose (RP2D) | 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. | first 4 weeks of Cycle 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses | Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. | 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) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joy H Zhu, MD, PhD | Halozyme Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Highlands Oncology Group | Fayetteville | Arkansas | 72707 | United States | ||
| California Pacific Medical Center |
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | PEGPH20 1.0 μg/kg | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| PEGPH20 | Drug | (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 |
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| Placebo | Drug | (Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment). |
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| Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | 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) |
| Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses | Blood samples were collected for pharmacokinetic assessment. | 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) |
| Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. | 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) |
| Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses | Blood samples were collected for pharmacokinetic assessment. | 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) |
| Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. | 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) |
| Apparent Half-life (t1/2) Following Single PEGPH20 Doses | 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. | 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) |
| t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | 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) |
| 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 | Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule. | 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) |
| AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | 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) |
| Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration | 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. | Baseline; post-Baseline (average treatment duration of 94.6 days) |
| H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies | 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. | Screening; Cycle 1 Week 7 |
| Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity | 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. | Baseline; up to 32 weeks for each individual participant (end of Cycle 7) |
| Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites | 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. | Baseline; 24 hours hours; end of Cycle 1 (Week 7) |
| Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites | 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. | Baseline; 24 hours hours; end of Cycle 1 (Week 7) |
| Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 | 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.) | up to approximately 2 years 4 months |
| Objective Response Rate | 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. | up to approximately 2 years 4 months |
| Disease Control Rate | 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. | up to approximately 2 years 4 months |
| Progression-free Survival (PFS) | 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. | from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months) |
| Overall Survival | Overall survival was defined as the time from the time of the first dose of PEGPH20 until death. | from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months) |
| Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9) | CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. | up to the end of Cycle 10 (up to Week 44) |
| Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml | CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. | up to the end of Cycle 10 (up to Week 44) |
| Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders | 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. | up to the end of Cycle 10 (up to Week 44) |
| San Francisco |
| California |
| 94120 |
| United States |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| UMDNJ - New Jersey Medical School | Newark | New Jersey | 07103 | United States |
| NSLIJ Health System, Monter Cancer Center | New Hyde Park | New York | 11040 | United States |
| Mount Sinai School of Medicine | New York | New York | 10029 | United States |
| SUNY Upstate Medical University | Syracuse | New York | 13210 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 90108 | United States |
| Chelyabinsk Regional Clinical Oncology Center | Chelyabinsk | Russia |
| Russian Oncological Research Center n.a. N.N. Blokhin | Moscow | Russia |
| Medical Radiological Research Center | Obninsk | Russia |
| Omsk Regional Budget Medical Institution | Omsk | Russia |
| FG001 | PEGPH20 1.6 μg/kg | 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. |
| FG002 | PEGPH20 3.0 μg/kg | 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. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | PEGPH20 1.0 μg/kg | 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. |
| BG001 | PEGPH20 1.6 μg/kg | 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. |
| BG002 | PEGPH20 3.0 μg/kg | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
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| Primary | Number of Participants With a Dose-limiting Toxicity (DLT) | 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. | 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. | Posted | Count of Participants | Participants | first 4 weeks of Cycle 1 |
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| Primary | Recommended Phase 2 Dose (RP2D) | 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. | 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 | Posted | Number | micrograms per kilogram (μg/kg) | first 4 weeks of Cycle 1 |
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| Secondary | Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses | Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. | Intent-to-Treat Population: all enrolled participants | Posted | Mean | Standard Deviation | units per milliliter | 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) |
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| Secondary | Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | Intent-to-Treat Population: all enrolled participants. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | units per milliliter | 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) |
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| Secondary | Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses | Blood samples were collected for pharmacokinetic assessment. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | units per milliliter | 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) |
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| Secondary | Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | Units per milliliter | 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) |
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| Secondary | Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses | Blood samples were collected for pharmacokinetic assessment. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Median | Full Range | hours | 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) |
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| Secondary | Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Median | Full Range | hours | 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) |
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| Secondary | Apparent Half-life (t1/2) Following Single PEGPH20 Doses | 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. | 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. | Posted | Mean | Standard Deviation | hours | 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) |
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| Secondary | t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | hours | 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) |
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| Secondary | 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 | Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule. | Intent-to-Treat Population | Posted | Mean | Standard Deviation | Units*hour/milliliter | 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) |
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| Secondary | AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks | 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. | Intent-to-Treat Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | Units*hour/milliliter | 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) |
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| Secondary | Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration | 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. | 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. | Posted | Mean | Standard Deviation | nanograms per milliliter | Baseline; post-Baseline (average treatment duration of 94.6 days) |
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| Secondary | H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies | 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. | 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. | Posted | Number | score on a scale | Screening; Cycle 1 Week 7 |
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| Secondary | Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity | 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. | 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. | Posted | Mean | Standard Deviation | percent change | Baseline; up to 32 weeks for each individual participant (end of Cycle 7) |
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| Secondary | Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites | 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. | 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. | Posted | Mean | Standard Deviation | milliliters (mL) per minute per 100 mL | Baseline; 24 hours hours; end of Cycle 1 (Week 7) |
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| Secondary | Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites | 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. | 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. | Posted | Mean | Standard Deviation | milliliters | Baseline; 24 hours hours; end of Cycle 1 (Week 7) |
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| Secondary | Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 | 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.) | 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. | Posted | Count of Participants | Participants | up to approximately 2 years 4 months |
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| Secondary | Objective Response Rate | 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. | 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. | Posted | Count of Participants | Participants | up to approximately 2 years 4 months |
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| Secondary | Disease Control Rate | 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. | 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. | Posted | Count of Participants | Participants | up to approximately 2 years 4 months |
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| Secondary | Progression-free Survival (PFS) | 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. | 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. | Posted | Median | 95% Confidence Interval | days | from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months) |
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| Secondary | Overall Survival | Overall survival was defined as the time from the time of the first dose of PEGPH20 until death. | 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. | Posted | Median | 95% Confidence Interval | days | from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months) |
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| Secondary | Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9) | CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. | 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. | Posted | Mean | Standard Deviation | Units per milliliter (U/ml) | up to the end of Cycle 10 (up to Week 44) |
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| Secondary | Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml | CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. | 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. | Posted | Mean | Standard Deviation | U/ml | up to the end of Cycle 10 (up to Week 44) |
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| Secondary | Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders | 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. | 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. | Posted | Mean | Standard Deviation | U/ml | up to the end of Cycle 10 (up to Week 44) |
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Not provided
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PEGPH20 1.0 μg/kg | 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. | 4 | 4 | 2 | 4 | 4 | 4 |
| EG001 | PEGPH20 1.6 μg/kg | 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. | 4 | 4 | 1 | 4 | 4 | 4 |
| EG002 | PEGPH20 3.0 μg/kg | 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. | 17 | 20 | 13 | 20 | 19 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Duodenal obstruction | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Splenic infarction | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Eyelid pain | Eye disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Gastrointestinal sounds abnormal | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Lip oedema | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Lip pain | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Tongue discolouration | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Application site rash | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Catheter site erythema | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Early satiety | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Injection site extravasation | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Thirst | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Candidiasis | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Contrast media reaction | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Eastern Cooperative Oncology Group performance status worsened | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Respiratory rate increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Fluid retention | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Glucose tolerance impaired | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Muscle atrophy | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Non-systematic Assessment |
| |
| Basal ganglia infarction | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Anger | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Urinary hesitation | Renal and urinary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Penile oedema | Reproductive system and breast disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Scrotal oedema | Reproductive system and breast disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dimitrios Chondros, M.D., Chief Medical Officer | Halozyme Therapeutics | 858-794-8889 | dchondros@halozyme.com |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| C000632509 | PEGPH20 |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 |
| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 |
| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
|
|
|
|
|
|
|
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| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| OG001 | PEGPH20 1.6 μg/kg | 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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| PEGPH20 1.6 μg/kg |
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. |
| OG002 | PEGPH20 3.0 μg/kg | 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. |
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| OG001 | Non-responders | 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. |
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