A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer (ALPINE)

• ClinicalTrials.gov Identifier: NCT01647828
• Recruitment Status: Completed
• First Posted: July 24, 2012
• Results First Posted: February 15, 2023
• Last Update Posted: February 15, 2023
• Sponsor: OncoMed Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )

Tracking Information

• First Submitted Date: July 11, 2012
• First Posted Date: July 24, 2012
• Results First Submitted Date: March 12, 2018
• Results First Posted Date: February 15, 2023
• Last Update Posted Date: February 15, 2023
• Study Start Date: October 2012
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2023)

• Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: July 19, 2012)

• Dose limiting toxicities (DLT) of OMP-59R5 in combination with gemcitabine [ Time Frame: Subjects will be treated and observed for DLT through the end of the first cycle (28 days), assessed up to 7 months ]
  The maximum tolerated dose (MTD) will be determined in patients treated with OMP-59R5 in combination with gemcitabine on Days 1, 8 and 15 of every 28-day cycle
• Progression-free survival (PFS) [ Time Frame: every 8 weeks till disease progression or start of new anti-cancer therapy, assessed up to 22 months ]
  If subjects experience unacceptable toxicities clearly related to one of the two drugs, they may continue the other drug alone until disease progression, or withdrawal of consent or unacceptable toxicity. Subjects who are discontinued from OMP-59R5 treatment will enter Follow-up period, be followed for survival and any subsequent anti-cancer therapies. Additionally, subjects who discontinue OMP-59R5 treatment for any reason other than disease progression will be followed with tumor assessment every 8 weeks/56 days

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: July 19, 2012)

• Pharmacokinetics (PK) of OMP-59R5 when given in combination with gemcitabine [ Time Frame: Up to 14 days after the first dose in Cycle 1, pre- and 5 minutes post- dose on Day 15 of Cycle 2, and Day 1 of every other cycle starting from Cycle 3, and up to 14 days after the last dose, assessed up to 24 months ]
  Apparent half life, AUC, clearance, volume of distribution
• Overall survival (OS), 6 months OS [ Time Frame: throughout the study and every 3 months after treatment discontinuation, assessed over 24 months ]
  Study visits are scheduled to occur every 7 (± 2) days for the first 3 weeks of each 4-week cycle. Survival follow-up information and subsequent anti-cancer therapies will be collected every 3 months until death, loss to follow-up, or study termination by the sponsor.
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: every week during the first 3 weeks of a 4 week cycle, assessed over 24 months ]
  Safety and tolerability of OMP-59R5 in combination with gemcitabine in subjects with stage IV pancreatic cancer (Phase 1b and 2 portions in subjects receiving OMP-59R5 with gemcitabine)
• Overall response rate (ORR) [ Time Frame: Every 8 weeks assessed up to 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer
• Official Title: A Phase 1b/2 Study of OMP-59R5 in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Stage IV Pancreatic Cancer

Intervention

• Drug: OMP-59R5
  OMP-59R5 administered intravenously
• Drug: Gemcitabine
  administered intravenously
• Drug: Placebo
  administered IV
• Drug: Nab-Paclitaxel
  administered intravenously
  Other Name: Abraxane

Study Arms

• Experimental: OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
  OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
  Interventions:

  • Drug: OMP-59R5
  • Drug: Gemcitabine
  • Drug: Nab-Paclitaxel
• Experimental: Gemcitabine and Nab-Paclitaxel plus Placebo
  Gemcitabine and Nab-Paclitaxel plus Placebo
  Interventions:

  • Drug: Gemcitabine
  • Drug: Placebo
  • Drug: Nab-Paclitaxel

• Publications *: Hu ZI, Bendell JC, Bullock A, LoConte NK, Hatoum H, Ritch P, Hool H, Leach JW, Sanchez J, Sohal DPS, Strickler J, Patel R, Wang-Gillam A, Firdaus I, Yu KH, Kapoun AM, Holmgren E, Zhou L, Dupont J, Picozzi V, Sahai V, O'Reilly EM. A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. Cancer Med. 2019 Sep;8(11):5148-5157. doi: 10.1002/cam4.2425. Epub 2019 Jul 26.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 16, 2016): 217
• Original Estimated Enrollment (submitted: July 19, 2012): 154
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 exclusion criteria will not be eligible for participation in the study:

1. Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas.
2. Known brain metastases.
3. Prior therapy, including systemic therapy, surgical resection or radiation for newly diagnosed stage IV pancreatic cancer.
4. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
5. Any disorder that would significantly compromise protocol compliance.
6. Prior non-pancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery and/or radiotherapy alone must be in remission ≥3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.
7. Known human immunodeficiency virus (HIV) infection.
8. Females who are pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01647828
• Other Study ID Numbers: 59R5-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: OncoMed Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Eileen M O'Reilly, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Mereo BioPharma
• Verification Date: January 2023