Stage IV Pancreatic Cancer
Conditions
Keywords
Newly diagnosed Stage IV Pancreatic Cancer
Brief summary
The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 in combination with nab-paclitaxel and gemcitabine followed by a Phase 2, multicenter, randomized, placebo-controlled portion to evaluate the efficacy and safety of OMP-59R5 in combination with nab-paclitaxel and gemcitabine in subjects with previously untreated stage IV pancreatic cancer.
Interventions
DRUGOMP-59R5
OMP-59R5 administered intravenously
DRUGGemcitabine
administered intravenously
DRUGPlacebo
administered IV
DRUGNab-Paclitaxel
administered intravenously
Sponsors
OncoMed Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following major inclusion criteria to be eligible for the study: 1. 18 years of age or older 2. Histologically or cytologically documented stage IV ductal adenocarcinoma of the pancreas. 3. Performance Status (ECOG) 0 or 1 4. FFPE tumor tissue from metastatic site(s 5. Adequate organ function 6. Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation. 7. For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration. 8. Male subjects must be surgically sterile or must agree to use physician-approved contraception from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
Exclusion criteria
Subjects who meet any of the following major
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | Up to 1 year in absence of unacceptable toxicity or disease progression. | Number of participants with dose-limiting toxicities when administered OMP-59R5 every of other week (Days 1 and 15) in combination with nab-paclitaxel (Nab-P) 125 mg/m2 and gemcitabine (Gem) 1000 mg/m2 on Days 1, 8, and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer. In the event that no DLTs are observed, maximum tested dose would be considered the Maximum Tolerated Dose (MTD). |
| Phase 2: Overall Survival (ITT Population) | Up to 1 year in absence of unacceptable toxicity or disease progression. | To determine the clinical benefit, as measured by overall survival (OS) ofthe addition of OMP-59R5 to nab-paclitaxel and gemcitabine in all subjects who are receiving first-line therapy for stage IV pancreatic cancer. |
| Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Up to 1 year in absence of unacceptable toxicity or disease progression. | To determine the clinical benefit, as measured by OS of the addition of OMP-59R5 to Nab-P+Gem across the 4 subject subsets: subjects with Notch3 ≥ 25th percentile, subjects with Notch3 ≥ 50th percentile, subjects with Notch3 ≥ 75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer with Notch3 high expression level. |
Countries
United States
Participant flow
Pre-assignment details
Phase 1b: A total of 40 subjects were planned and enrolled. Phase 2: Approximately 160 subjects were planned to be randomized. A total of 177 subjects were enrolled/randomized. Total: 217 subjects were enrolled/randomized (Phase 1b and Phase 2)
Participants by arm
| Arm | Count |
|---|---|
| P1B: OMP-59R5 2.5 mg/kg + Gem Cohort 1: Subjects receive OMP-59R5 2.5 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 5 |
| P1B: OMP-59R5 5 mg/kg + Gem Cohort 2: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 4 |
| P1B: OMP-59R5 5 mg/kg + Nab-P + Gem Cohort 3: Subjects receive OMP-59R5 5 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 4 |
| P1B: OMP-59R5 7.5 mg/kg + Nab-P + Gem Cohort 4: Subjects receive OMP-59R5 7.5 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 6 |
| P1B: OMP-59R5 10 mg/kg + Nab-P + Gem Cohort 5: Subjects receive OMP-59R5 10 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 6 |
| P1B: OMP-59R5 12.5 mg/kg + Nab-P + Gem Cohort 6: Subjects receive OMP-59R5 12.5 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 3 |
| P1B: OMP-59R5 15 mg/kg + Nab-P + Gem Expansion Cohort: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 12 |
| P2: Placebo + Nab-P + Gem Placebo Arm: Subjects receive placebo (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 88 |
| P2: OMP-59R5 15 mg/kg + Nab-P + Gem Active Arm: Subjects receive OMP-59R5 15 mg/kg (administered on Day 1 and Day 15 of each 28-day treatment cycle) along with 125 mg/m2 Nab-Paclitaxel (Day 1, Day 8, and Day 15 of every 28-day treatment cycle) and 1000 mg/mg2 of Gemcitabine (Day 1, Day 8, and Day 15 of every 28-day treatment cycle). | 89 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 4 | 5 | 6 | 3 | 10 | 60 | 71 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 26 | 16 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | P1B: OMP-59R5 2.5 mg/kg + Gem | P1B: OMP-59R5 5 mg/kg + Gem | P1B: OMP-59R5 5 mg/kg + Nab-P + Gem | P1B: OMP-59R5 7.5 mg/kg + Nab-P + Gem | P1B: OMP-59R5 10 mg/kg + Nab-P + Gem | P1B: OMP-59R5 12.5 mg/kg + Nab-P + Gem | P1B: OMP-59R5 15 mg/kg + Nab-P + Gem | P2: Placebo + Nab-P + Gem | P2: OMP-59R5 15 mg/kg + Nab-P + Gem | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Age | 66 years | 68 years | 68 years | 66 years | 67 years | 58 years | 59 years | 66 years | 66 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 3 Participants | 11 Participants | 81 Participants | 87 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants | 7 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 10 Participants | 80 Participants | 76 Participants | 191 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 34 Participants | 39 Participants | 91 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 8 Participants | 54 Participants | 50 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 5 | 4 / 4 | 4 / 4 | 5 / 6 | 6 / 6 | 3 / 3 | 10 / 12 | 60 / 88 | 71 / 89 |
| other Total, other adverse events | 5 / 5 | 4 / 4 | 4 / 4 | 6 / 6 | 6 / 6 | 3 / 3 | 12 / 12 | 85 / 85 | 87 / 87 |
| serious Total, serious adverse events | 4 / 5 | 1 / 4 | 1 / 4 | 3 / 6 | 4 / 6 | 1 / 3 | 9 / 12 | 51 / 85 | 58 / 87 |
Outcome results
Primary
Phase 2: Median OS by Notch 3 Percentile (ITT Population)
To determine the clinical benefit, as measured by OS of the addition of OMP-59R5 to Nab-P+Gem across the 4 subject subsets: subjects with Notch3 ≥ 25th percentile, subjects with Notch3 ≥ 50th percentile, subjects with Notch3 ≥ 75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer with Notch3 high expression level.
Time frame: Up to 1 year in absence of unacceptable toxicity or disease progression.
Population: The Intent-to-Treat (ITT) Population comprised all participants who received at least 1 partial dose of tarextumab. Here, Overall Number of Participants Analyzed = number of participants with Notch 3 ≥ 25th percentile, and Number Analyzed = number of participants in each Notch 3 percentile subset.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 75th percentile | 187.5 Days |
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 50th percentile | 220.5 Days |
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 25th percentile | 206.0 Days |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 75th percentile | 228.0 Days |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 50th percentile | 151.0 Days |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase 2: Median OS by Notch 3 Percentile (ITT Population) | Notch 3 ≥ 25th percentile | 165.0 Days |
Primary
Phase 2: Overall Survival (ITT Population)
To determine the clinical benefit, as measured by overall survival (OS) ofthe addition of OMP-59R5 to nab-paclitaxel and gemcitabine in all subjects who are receiving first-line therapy for stage IV pancreatic cancer.
Time frame: Up to 1 year in absence of unacceptable toxicity or disease progression.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase 2: Overall Survival (ITT Population) | Number of subjects who died | 60 participants |
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase 2: Overall Survival (ITT Population) | Number of subjects who did not die | 28 participants |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase 2: Overall Survival (ITT Population) | Number of subjects who died | 71 participants |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase 2: Overall Survival (ITT Population) | Number of subjects who did not die | 18 participants |
Primary
Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT)
Number of participants with dose-limiting toxicities when administered OMP-59R5 every of other week (Days 1 and 15) in combination with nab-paclitaxel (Nab-P) 125 mg/m2 and gemcitabine (Gem) 1000 mg/m2 on Days 1, 8, and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer. In the event that no DLTs are observed, maximum tested dose would be considered the Maximum Tolerated Dose (MTD).
Time frame: Up to 1 year in absence of unacceptable toxicity or disease progression.
Population: The DLT Evaluable Population comprised all participants who received at least 1 partial dose of tarextumab during the Phase 1b dose escalation portion of the study (enrolled before the MTD was determined) and who completed Day 15 of Cycle 1 tarextumab administration or discontinued due to drug-related toxicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| P1B: OMP-59R5 2.5 mg/kg + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 5 mg/kg + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 5 mg/kg + Nab-P + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 7.5 mg/kg + Nab-P + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 10 mg/kg + Nab-P + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 12.5 mg/kg + Nab-P + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
| P1B: OMP-59R5 15 mg/kg + Nab-P + Gem | Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | 1 Participants |