A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
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| ClinicalTrials.gov Identifier: NCT03193190 |
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Recruitment Status :
Recruiting
First Posted : June 20, 2017
Last Update Posted : June 2, 2023
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Pancreatic Adenocarcinoma | Drug: Nab-Paclitaxel Drug: Gemcitabine Drug: Oxaliplatin Drug: Leucovorin Drug: Fluorouracil Drug: Atezolizumab Drug: Cobimetinib Drug: PEGPH20 Drug: BL-8040 Drug: Selicrelumab Drug: Bevacizumab Drug: RO6874281 Drug: AB928 Drug: Tiragolumab Drug: Tocilizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 340 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | July 5, 2017 |
| Estimated Primary Completion Date : | June 1, 2024 |
| Estimated Study Completion Date : | June 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)
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. |
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. |
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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/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.
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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. |
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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/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.
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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. |
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Experimental: Cohort 1: Atezolizumab + Chemotherapy + AB928
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.
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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: AB928 AB928 will be administered as per the schedule specified in the respective arm. |
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Experimental: Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab
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.
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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: Tiragolumab Tiragolumab will be administered as per the schedule specified in the respective arm. |
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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. |
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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. |
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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. |
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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 |
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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 |
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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/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. |
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. |
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Experimental: Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab
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.
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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: Tocilizumab Tocilizumab will be administered as per the schedule specified in the respective arm. |
- 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 5-7 years) ]
- Percentage of Participants With Adverse Events (AEs) [ Time Frame: From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 5-7 years) ]
- 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 5-7 years) ]
- Overall Survival [ Time Frame: From randomization up to death from any cause (up to approximately 5-7 years) ]
- Percentage of Participants who are Alive at Month 6 [ Time Frame: Month 6 ]
- 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 5-7 years) ]
- 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 5-7 years) ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | 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:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193190
| 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 |
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| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03193190 |
| Other Study ID Numbers: |
WO39608 2016-004126-42 ( EudraCT Number ) |
| First Posted: | June 20, 2017 Key Record Dates |
| Last Update Posted: | June 2, 2023 |
| Last Verified: | June 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Leucovorin Paclitaxel Bevacizumab Gemcitabine Fluorouracil Oxaliplatin Atezolizumab Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antimetabolites, Antineoplastic Antimetabolites Immunosuppressive Agents Immunologic Factors Antidotes Protective Agents |