Clinical Trial - NCT03289962

A Study of RO7198457 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors

Recruiting

Sponsor: Genentech, Inc.

Collaborators: Biontech RNA Pharmaceuticals GmbH

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03289962

Protocol Info

Short Description: Phase 1a/1b RO7198457 + Atezolizumab in Advanced or Metastatic Tumors
Long Description: A Phase 1a/1b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RO7198457 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Tumors
MGH Status: Open
Sponsor: Genentech
Disease Program: Phase I

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

This is a Phase 1a/1b, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, immune response, and pharmacokinetics of RO7198457 as a single agent and in combination with atezolizumab (MPDL3280A, an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody).
Condition Title Intervention Phase
Melanoma Non-Small Cell Lung Cancer Bladder Cancer Colorectal Cancer Triple Negative Breast Cancer Renal Cancer Head and Neck Cancer Other Solid Cancers RO7198457 Atezolizumab Phase 1
Study Type Interventional
Official Title A Phase 1a/1b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RO7198457 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Tumors

Primary Outcome Measures

Percentage of Participants with Dose-Limiting Toxicities (DLTs) [Time Frame: Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21] [Designated as safety issue: ]

MTD/Recommended Phase 2 Dose (RP2D) of RO7198457 [Time Frame: Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21] [Designated as safety issue: ]

Percentage of Participants with Adverse Events (AEs) by Severity According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Time Frame: Baseline up to end of the study (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants with Immune-Mediated Adverse Events (imAEs) by Severity According to NCI CTCAE Version 5.0 [Time Frame: Baseline up to end of the study (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants by Number of Treatment Cycles Received [Time Frame: Baseline up to end of the study (up to approximately 3 years)] [Designated as safety issue: ]

Dose Intensity of RO7198457 [Time Frame: Baseline up to end of the study (up to approximately 3 years)] [Designated as safety issue: ]

Change from baseline in targeted vital signs [Time Frame: Baseline up to end of study (up to approximately 3 years)] [Designated as safety issue: ]

Change from baseline in targeted clinical laboratory test results [Time Frame: Baseline up to end of study (up to approximately 3 years)] [Designated as safety issue: ]

Change from baseline in ECGs [Time Frame: Baseline up to end of study (up to approximately 3 years)] [Designated as safety issue: ]


Secondary Outcome Measures

Plasma Concentration of (R)-N,N,N-Trimethyl-2,3-Dioleyloxy-1-Propanaminium Chloride (DOTMA) [Time Frame: Pre-infusion (0 hour [hr]) until treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Plasma Concentration of Ribonucleic Acid (RNA) [Time Frame: Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Serum Concentration of Atezolizumab [Time Frame: Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants with Induction of Antigen-Specific T-Cell Responses in Peripheral Blood [Time Frame: Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Immune-Related Cytokine Levels [Time Frame: Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST v1.1) [Time Frame: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

Duration of Response (DoR) According to RECIST v1.1 [Time Frame: From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants with Objective Response of CR or PR According to Immune-Modified RECIST [Time Frame: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

DoR According to Immune-Modified RECIST [Time Frame: From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

Progression-Free Survival (PFS) According to RECIST v1.1 [Time Frame: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)] [Designated as safety issue: ]

Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [Time Frame: Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years)] [Designated as safety issue: ]

Estimated Enrollment: 770
Study Start Date: December 2017
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: September 2020
Arms Assigned Interventions

Experimental:Phase 1a Dose-Escalation: RO7198457

Participants will receive RO7198457 at escalated dosages.
Drug:RO7198457
RO7198457 will be administered by intravenous (IV) infusion, in 21-day cycles.

Experimental:Phase 1b Dose-Escalation: RO7198457 + Atezolizumab

Participants will receive RO7198457 at escalated dosages along with atezolizumab at a fixed dose of 1200 milligrams (mg).
Drug:Atezolizumab
Atezolizumab will be administered by IV infusion on Day 1 of every 21-day cycle.

Experimental:Phase 1b Exploration: RO7198457 + Atezolizumab

Non-small cell lung cancer (NSCLC) or Melanoma cancer immunotherapy (CIT)-treated participants will receive RO7198457 (at dosage lower than maximum tolerated dose [MTD] based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.

Experimental:Phase 1b Expansion: RO7198457 + Atezolizumab

Participants with different indications as per inclusion criteria, will receive RO7198457 (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.

Experimental:Phase 1b Expansion: RO7198457 + Atezolizumab (Serial Biopsy)

CIT-naive participants with selected tumor types who consent to optional serial biopsies will receive RO7198457 (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy greater than or equal to (>=12 weeks)
  • Adequate hematologic and end-organ function
  • Measured or calculated creatinine clearance >=50 milliliters per minute (mL/min) on the basis of the Cockcroft-Gault glomerular filtration rate estimation

Cancer-Specific Inclusion Criteria:

  • Participants with histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care
  • Participants with confirmed availability of representative tumor specimens in formalin-fixed, paraffin-embedded (FFPE) blocks (preferred), or sectioned tissue
  • Participants with measurable disease per RECIST v1.1

Additional Inclusion Criteria for Participants in Each Indication-Specific Exploration/Expansion Cohort of Phase 1b:

  • NSCLC Cohorts (CIT-Naïve): Participants with histologically confirmed incurable, advanced NSCLC not previously treated with anti-PD−L1/PD-1 and/or with anti-CTLA−4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD−L1/PD-1 antibody is considered an acceptable treatment option (if CIT [including anti-PD−L1/PD-1 agents] is approved as treatment for NSCLC by local regulatory authorities).
  • NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable, advanced NSCLC previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
  • Triple negative breast cancer (TNBC) Cohort (CIT-Naïve): Participants with histologically confirmed incurable, advanced estrogen receptor (ER)-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the breast (triple-negative) not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
  • Colorectal cancer (CRC) Cohort (CIT-Naïve): Participants with histologically confirmed incurable, advanced adenocarcinoma of the colon or rectum not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
  • Head and neck squamous cell carcinoma (HNSCC) Cohort (CIT-Naïve): Participants with histologically confirmed inoperable, locally advanced or metastatic, recurrent, or persistent HNSCC (oral cavity, oropharynx, hypopharnyx, or larynx) not amenable to curative therapy not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
  • Urothelial carcinoma (UC) Cohort (CIT-Naïve): Participants with histologically confirmed incurable, advanced transitional cell carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, and urethra, not previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD−L1 antibody is considered an acceptable treatment option, if CIT (including anti-PD−L1/PD-1 agents) is approved as treatment for UC by local regulatory authorities
  • UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
  • Renal cell carcinoma (RCC) Cohort (CIT-Naïve): Participants with histologically confirmed incurable, advanced RCC with component of clear cell histology and/or component of sarcomatoid histology not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
  • Melanoma Cohort (CIT-Naïve in metastatic setting): Participants with histologically confirmed incurable, advanced melanoma not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved) in the metastatic setting
  • Melanoma Cohort (CIT-Treated): Participants with histologically confirmed incurable, advanced melanoma previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)

Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of Phase 1b:

  • Participants must have one of the locally advanced or metastatic solid tumor types specified in the protocol.
  • Participants must have accessible lesion(s) that permit a total of two to three biopsies (pretreatment and on-treatment) or one biopsy (on-treatment, if archival tissue can be submitted in place of a pre-treatment biopsy) without unacceptable risk of a significant procedural complication. RECIST lesions should not be biopsied.

Exclusion Criteria:

  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the course of the study
  • Any other diseases, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the participant at high risk from treatment complications
  • Previous splenectomy
  • Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)
  • Any medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study Cancer-Specific Exclusion Criteria
  • Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study treatment, with the exceptions as mentioned in the protocol
  • Eligibility based on prior treatment with CIT depends on the mechanistic class of the drug and the cohort for which the participant is being considered, as described below. In addition, all criteria pertaining to adverse events attributed to prior cancer therapies must be met

All Cohorts (Dose-Escalation in Phase 1a and Dose-Escalation, Backfill, and Expansion in Phase 1b):

  • Prior neoantigen-specific or whole-tumor cancer vaccines are not allowed, with the exception as specified in protocol
  • Prior treatment with cytokines is allowed provided that at least 6 weeks or 5 half-lives of the drug, whichever is shorter, have elapsed between the last dose and the proposed Cycle 1, Day 1
  • Prior treatment with immune checkpoint inhibitors, immunomodulatory monoclonal antibody (mAbs), and/or mAb-derived therapies is allowed provided that at least 6 weeks (Phase 1a) or 3 weeks (Phase 1b) have elapsed between the last dose and the proposed Cycle 1, Day 1, with the exceptions as specified in protocol Phase Ib Dose-Exploration/Expansion Group Only Cohorts
  • In the CIT-Naïve expansion cohort in Phase Ib, prior treatment with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved), is not allowed.
  • In the melanoma CIT-naïve expansion cohort in Phase Ib, prior treatment with anti-PD- L1/PD-1 and/or anti-CTLA-4 (investigational or approved) in the metastatic, is not allowed.
  • Prior treatment with immunomodulators, including toll-like receptor (TLR) agonists, inhibitors of indoleamine 2,3-dioxygenase (IDO)/ tryptophan-2,3-dioxygenase (TDO), or agonists of OX40, is allowed provided that at least 5 half-lives of the drug or a minimum of 3 weeks have elapsed between the last dose of the prior treatment and the proposed Cycle 1, Day 1, with the exception as specified in protocol
  • Any history of an immune-related Grade 4 adverse event attributed to prior CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)
  • Any history of an immune-related Grade 3 adverse event attributed to prior CIT (other than hypothyroidism managed with replacement therapy) that resulted in permanent discontinuation of the prior immunotherapeutic agent and/or occurred less than or equal to (<=) 6 months prior to Cycle 1 Day 1
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade <=1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy
  • All immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) must have resolved completely to baseline
  • Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death
  • Uncontrolled hypercalcemia
  • Participant has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to screening

Treatment-Specific Exclusion Criteria:

  • History of autoimmune disease with caveats as specified in protocol
  • Treatment with monoamine oxidase inhibitors (MAOIs) within 3 weeks prior to Cycle 1, Day 1
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1
  • History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Positive test for human immunodeficiency virus (HIV) infection
  • Active hepatitis B, hepatitis C
  • Known active or latent tuberculosis infection
  • Severe infections within 4 weeks prior to Cycle 1, Day 1
  • Recent infections not meeting the criteria for severe infections within 2 weeks prior to Cycle 1, Day 1
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Known hypersensitivity to the active substance or to any of the excipients in the vaccine
  • Phase 1b and crossover only: History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; Known hypersensitivity to Chinese Hamster Ovary (CHO)-cell products; Allergy or hypersensitivity to components of the atezolizumab formulation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03289962

Locations

  • United States, Arizona
    • HonorHealth Research Institute - Bisgrove Scottsdale, Arizona, United States, 85258
  • United States, California
    • The Angeles Clinic Los Angeles, California, United States, 90025
    • UCSF Comprehensive Cancer Ctr San Francisco, California, United States, 94115
    • Stanford Cancer Center Stanford, California, United States, 94305-5820
  • United States, Colorado
    • University of Colorado Aurora, Colorado, United States, 80045-2517
  • United States, Connecticut
    • Yale University Cancer Center, Smilow Cancer Hospital; Medical Oncology New Haven, Connecticut, United States, 06511
  • United States, District of Columbia
    • Georgetown University Washington, District of Columbia, United States, 20007
  • United States, Massachusetts
    • Massachusetts General Hospital. Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana Farber Can Ins Boston, Massachusetts, United States, 02215
  • United States, Nevada
    • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley Las Vegas, Nevada, United States, 89169
  • United States, New York
    • Columbia University Medical Center; Clinical Research Management Office New York, New York, United States, 10032
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, Oklahoma
    • University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma, United States, 73104
  • United States, Oregon
    • Providence Oncology and Hematology Care Eastside Portland, Oregon, United States, 97213
  • United States, Pennsylvania
    • University of Pittsburgh Medical Center Pittsburgh, Pennsylvania, United States, 15213
  • United States, Tennessee
    • Sarah Cannon Res Inst; TN Onc Nashville, Tennessee, United States, 37203
  • United States, Washington
    • Seattle Cancer Care Alliance Seattle, Washington, United States, 98109
  • Belgium,
    • UZ Gent Gent, , Belgium, 9000
    • CHU Sart-Tilman Liège, , Belgium, 4000
    • Sint Augustinus Wilrijk Wilrijk, , Belgium, 2610
  • Canada, Ontario
    • The Ottawa Hospital Cancer Centre; Oncology Ottawa, Ontario, Canada, K1H 8L6
    • Princess Margaret Cancer Center; Department of Radiation Oncology Toronto, Ontario, Canada, M5G 2M9
  • Germany,
    • Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung Essen, , Germany, 45122
    • LungenClinic Großhansdorf Großhansdorf, , Germany, 22927
    • Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg Heidelberg, , Germany, 69120
    • Fachklinik für Lungenerkrankungen Immenhausen, , Germany, 34376
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz Mainz, , Germany, 55101
  • Netherlands,
    • Antoni van Leeuwenhoek Ziekenhuis Amsterdam, , Netherlands, 1066 CX
    • LUMC Leiden, , Netherlands, 2300 ZA
    • Universitair Medisch Centrum Utrecht Utrecht, , Netherlands, 3584 CX
  • Spain, Navarra
    • Clinica Universitaria de Navarra; Servicio de oncología Pamplona, Navarra, Spain, 31008
  • Spain,
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona, , Spain, 08035
  • Sweden,
    • Karolinska Hospital; Oncology - Radiumhemmet Stockholm, , Sweden, 171 76
    • Akademiska sjukhuset, Onkologkliniken Uppsala, , Sweden, 75185
  • United Kingdom,
    • Barts & London School of Med; Medical Oncology London, , United Kingdom, EC1A 7BE
    • Southampton General Hospital; Medical Oncology Southampton, , United Kingdom, SO16 6YD
    • The Royal Marsden Hospital Sutton, , United Kingdom, SM2 5PT

Sponsors and Collaborators

Genentech, Inc.

Biontech RNA Pharmaceuticals GmbH

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03289962
Other Study ID Numbers: 2017-001475-23
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Genentech, Inc.:

Cancer vaccine

Neoantigen

Personalized

Atezolizumab

Vaccine

Immunotherapy

Anti-PDL1

Checkpoint Inhibitor

Personalized vaccine

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Colorectal Neoplasms

Head and Neck Neoplasms

Urinary Bladder Neoplasms

Triple Negative Breast Neoplasms

Kidney Neoplasms

Carcinoma, Renal Cell

Neoplasm Metastasis

Atezolizumab

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 16, 2019