Clinical Trial: NCT03193190 - My Cancer Genome

NCT03193190

Description:

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.

Related Conditions:

Pancreatic Ductal Adenocarcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03193190

Trial Eligibility

Document

Title

Brief Title: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)

Clinical Trial IDs

ORG STUDY ID: WO39608
SECONDARY ID: 2016-004126-42
NCT ID: NCT03193190

Conditions

Pancreatic Adenocarcinoma

Interventions

Drug	Synonyms	Arms
Nab-Paclitaxel		Cohort 1: Atezolizumab + Chemotherapy + AB928
Gemcitabine		Cohort 1: Atezolizumab + Chemotherapy + AB928
Oxaliplatin		Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)
Leucovorin		Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)
Fluorouracil		Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)
Atezolizumab		Cohort 1: Atezolizumab + Chemotherapy + AB928
Cobimetinib		Cohort 2: Atezolizumab + Cobimetinib
PEGPH20		Cohort 2: Atezolizumab + PEGPH20
BL-8040		Cohort 2: Atezolizumab + BL-8040
Selicrelumab		Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab
Bevacizumab		Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab
RO6874281		Cohort 2: Atezolizumab + RO6874281 every 2 weeks
AB928		Cohort 1: Atezolizumab + Chemotherapy + AB928
Tiragolumab		Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab
Tocilizumab		Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab

Purpose

Trial Arms

Name	Type	Description	Interventions
Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)	Active Comparator	Cohort 1: Participants will receive Nab-Paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 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.	Nab-Paclitaxel Gemcitabine
Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab	Experimental	Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 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.	Nab-Paclitaxel Gemcitabine Atezolizumab Selicrelumab
Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab	Experimental	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/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.	Nab-Paclitaxel Gemcitabine Atezolizumab Bevacizumab
Cohort 1: Atezolizumab + Chemotherapy + AB928	Experimental	Cohort 1: Participant will receive AB928 150 mg orally once daily on Days 1 to 28 of each 28 day cycle; Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.	Nab-Paclitaxel Gemcitabine Atezolizumab AB928
Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab	Experimental	Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Tiragolumab 420 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.	Nab-Paclitaxel Gemcitabine Atezolizumab Tiragolumab
Cohort 2: Atezolizumab + Cobimetinib	Experimental	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.	Atezolizumab Cobimetinib
Cohort 2: Atezolizumab + PEGPH20	Experimental	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.	Atezolizumab PEGPH20
Cohort 2: Atezolizumab + BL-8040	Experimental	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.	Atezolizumab BL-8040
Cohort 2: Atezolizumab + RO6874281 every 2 weeks	Experimental	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.	Atezolizumab RO6874281
Cohort 2: Atezolizumab + RO6874281 every 3 weeks	Experimental	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.	Atezolizumab RO6874281
Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)	Active Comparator	Cohort 2: Participants who progressed on a prior fluoropyrimidine-based regimen will receive Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 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/m^2 IV on Days 1 and 15 of each 28 day cycle; Leucovorin 400 mg/m^2 IV on Days 1 and 15 of each 28 day cycle; Fluorouracil 400 mg/m^2 IV push on Days 1 and 15 of each 28 day cycle; and Fluorouracil 2400 mg/m^2 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.	Nab-Paclitaxel Gemcitabine Oxaliplatin Leucovorin Fluorouracil
Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab	Experimental	Cohort 1: Participants will receive Tocilizumab 8 mg/kg IV infusion on Day 1 of each 28 day cycle; Atezolizumab 1680 mg IV infusion on Day 1 of each 28 day cycle; Nab-paclitaxel 125 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.	Nab-Paclitaxel Gemcitabine Atezolizumab Tocilizumab

Eligibility Criteria

        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:

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage
             procedure (i.e., more than one time per month)

          -  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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
Time Frame:	From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
Time Frame:	From randomization up to the first occurrence of disease (up to approximately 3-5 years)
Safety Issue:
Description:

Measure:	Overall Survival
Time Frame:	From randomization up to death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:

Measure:	Percentage of Participants who are Alive at Month 6
Time Frame:	Month 6
Safety Issue:
Description:

Measure:	Duration of Response, as Determined by Investigator According to RECIST v1.1
Time Frame:	From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:

Measure:	Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1
Time Frame:	From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Safety Issue:
Description:

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Hoffmann-La Roche

Last Updated

August 5, 2021

Clinical Trials /

A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)