Purpose

A Phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of patients who have received no prior systemic therapy for metastatic PDAC, and Cohort 2 will consist of patients who have received one line of prior systemic therapy for PDAC. In each cohort, eligible patients will be assigned to one of several treatment arms.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
  • For patients in Cohort 1: no prior systemic treatment for PDAC
  • For patients in Cohort 2: disease progression during administration of either 5-FU− or gemcitabine-based first-line chemotherapy
  • Life expectancy greater than or equal to 3 months
  • Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • Adequate hematologic and end-organ function test results
  • Tumor accessible for biopsy
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Exclusion Criteria

  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Positive human immunodeficiency (HIV) test at screening or at any time prior to screening
  • Active hepatitis B or C virus infection or active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Prior allogeneic stem cell or solid organ transplantation
  • History of malignancy other than pancreatic carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)
Cohort 1: Participants will receive Nab-Paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle. Participants in the Cohort 1 control arm who experience disease progression will be given the option of enrolling into Cohort 2 (if open for enrollment), provided they meet eligibility criteria.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab
Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Selicrelumab 16 mg subcutaneous injection on Day 1 of Cycles 1−4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each 28-day cycle.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Selicrelumab
    Selicrelumab will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 1: Atezolizumab + Chemo + Selicrelumab + Bevacizumab
Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Bevacizumab 10 mg/kg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Selicrelumab 16 mg subcutaneous on Day 1 of Cycles 1−4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each 28-day cycle.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Selicrelumab
    Selicrelumab will be administered as per the schedule specified in the respective arm.
  • Drug: Bevacizumab
    Bevacizumab will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab
Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Bevacizumab 10 mg/kg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Bevacizumab
    Bevacizumab will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 1: Atezolizumab + Chemotherapy + Emactuzumab
Cohort 1: Participants will receive Emactuzumab 1000 mg IV infusion on Days 1 and 15 of each 28 day cycle; Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Emactuzumab
    Emactuzumab will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 2: Atezolizumab + Cobimetinib
Cohort 2: Participants will receive Cobimetinib 60 milligrams (mg) once daily orally on Days 1-21 of each 28-day cycle; and Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28-day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arm is open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Cobimetinib
    Cobimetinib will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 2: Atezolizumab + PEGPH20
Cohort 2: Participants will receive PEGPH20 3 micrograms per kilogram (mcg/kg) IV infusion on Days 1, 8 and 15 of each 21-day cycle; and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 2: Atezolizumab + BL-8040
Cohort 2: Participants will receive BL-8040 1.25 milligrams per kilogram (mg/kg) subcutaneously (SC) on Days 1-5 of the first week, followed by combination treatment consisting of BL-8040 1.25 mg/kg SC three times a week on non-consecutive days and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: BL-8040
    BL-8040 will be administered as per the schedule specified in the respective arm.
Experimental
Cohort 2: Atezolizumab + RO6874281 every 2 weeks
Cohort 2: Participants will receive Atezolizumab 840 mg IV infusion on days 1 and 15 of each 28 day cycle; RO6874281 will be administered 10 mg by IV infusion on day 1 and 15 mg on days 8, 15, and 22 for cycle 1 (28 day cycle). RO6874281 will be administered 15 mg by IV infusion on days 1 and 15 of each subsequent 28 day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: RO6874281
    RO6874281 will be administered as per the schedule specified in the respective arm
Experimental
Cohort 2: Atezolizumab + RO6874281 every 3 weeks
Cohort 2: Participants will receive Atezolizumab 1200 mg IV infusion on Day 1 of each 21 day cycle; and RO6874281 10 mg by IV infusion on day 1 of each 21 day cycle. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: RO6874281
    RO6874281 will be administered as per the schedule specified in the respective arm
Experimental
Cohort 2: Atezolizumab + Emactuzumab
Cohort 2: Participants will receive Emactuzumab 1000 mg IV infusion on day 1 of each 21 day cycle; and Atezolizumab 1200 mg IV infusion on Day 1 of each 21 day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Emactuzumab
    Emactuzumab will be administered as per the schedule specified in the respective arm.
Active Comparator
Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)
Cohort 2: Participants who progressed on a prior fluoropyrimidine-based regimen will receive Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle. Participants who progressed on a prior gemcitabine-based regimen will receive 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6). Participants will receive Oxaliplatin 85 mg/m2 IV on Days 1 and 15 of each 28 day cycle; Leucovorin 400 mg/m2 IV on Days 1 and 15 of each 28 day cycle; Fluorouracil 400 mg/m2 IV push on Days 1 and 15 of each 28 day cycle; and Fluorouracil 2400 mg/m2 IV continuous infusion over 46 hours on Days 1 and 2 and on Days 15 and 16 of each 28 day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Oxaliplatin
    Oxaliplatin will be administered as per the schedule specified in the respective arm.
  • Drug: Leucovorin
    Leucovorin will be administered as per the schedule specified in the respective arm.
  • Drug: Fluorouracil
    Fluorouracil will be administered as per the schedule specified in the respective arm.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

NCT ID
NCT03193190
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: WO39608 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.