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Trial record 3 of 3 for:    BioNTech | Recruiting, Not yet recruiting Studies

A Study of RO7198457 (Personalized Cancer Vaccine [PCV]) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors

This study is currently recruiting participants.
Verified October 2017 by Genentech, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03289962
First Posted: September 21, 2017
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Biontech RNA Pharmaceuticals GmbH
Information provided by (Responsible Party):
Genentech, Inc.
  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 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 Drug: RO7198457 Drug: Atezolizumab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

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 ]
  • MTD/Recommended Phase 2 Dose (RP2D) of RO7198457 [ Time Frame: Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21 ]
  • Percentage of Participants with Adverse Events (AEs) by Severity According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Baseline up to end of the study (up to approximately 3 years) ]
  • Percentage of Participants with Immune-Mediated Adverse Events (imAEs) by Severity According to NCI CTCAE Version 4.0 [ Time Frame: Baseline up to end of the study (up to approximately 3 years) ]
  • Percentage of Participants by Number of Treatment Cycles Received [ Time Frame: Baseline up to end of the study (up to approximately 3 years) ]
  • Dose Intensity of RO7198457 [ Time Frame: Baseline up to end of the study (up to approximately 3 years) ]

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) ]
  • Plasma Concentration of Ribonucleic Acid (RNA) [ Time Frame: Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years) ]
  • 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) ]
  • Immune-Related Cytokine Levels [ Time Frame: Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]

Estimated Enrollment: 572
Anticipated Study Start Date: December 7, 2017
Estimated Study Completion Date: September 11, 2020
Estimated Primary Completion Date: September 11, 2020 (Final data collection date for primary outcome measure)
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.
Other Name: PCV
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: RO7198457
RO7198457 will be administered by intravenous (IV) infusion, in 21-day cycles.
Other Name: PCV
Drug: Atezolizumab
Atezolizumab will be administered by IV infusion, in 21-day cycles.
Other Names:
  • Tecentriq
  • RO5541267
  • MPDL3280A
  • An engineered anti-PDL1 antibody
Experimental: Phase 1b Exploration: RO7198457 + Atezolizumab
Non-small cell lung cancer (NSCLC) 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.
Drug: RO7198457
RO7198457 will be administered by intravenous (IV) infusion, in 21-day cycles.
Other Name: PCV
Drug: Atezolizumab
Atezolizumab will be administered by IV infusion, in 21-day cycles.
Other Names:
  • Tecentriq
  • RO5541267
  • MPDL3280A
  • An engineered anti-PDL1 antibody
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.
Drug: RO7198457
RO7198457 will be administered by intravenous (IV) infusion, in 21-day cycles.
Other Name: PCV
Drug: Atezolizumab
Atezolizumab will be administered by IV infusion, in 21-day cycles.
Other Names:
  • Tecentriq
  • RO5541267
  • MPDL3280A
  • An engineered anti-PDL1 antibody
Experimental: Phase 1b Expansion: RO7198457 + Atezolizumab (Serial Biopsy)
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.
Drug: RO7198457
RO7198457 will be administered by intravenous (IV) infusion, in 21-day cycles.
Other Name: PCV
Drug: Atezolizumab
Atezolizumab will be administered by IV infusion, in 21-day cycles.
Other Names:
  • Tecentriq
  • RO5541267
  • MPDL3280A
  • An engineered anti-PDL1 antibody

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 Who Backfill Cleared Cohorts of Phase 1a and Phase 1b:

- Backfill cohort enrollment may be limited to participants whose tumors have PD-L1 and/or different levels of cluster of differentiation 8 (CD8) expression, as defined by the Sponsor

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 CIT (investigational or approved), including anti-PD−L1/programmed death-1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA−4), 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 NSCLC by local regulatory authorities
  • NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable, advanced NSCLC previously treated with CIT (investigational or approved) including anti-PD−L1/PD-1
  • Triple negative breast cancer (TNBC) Cohort: 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)
  • Colorectal cancer (CRC) Cohort: Participants with histologically confirmed incurable, advanced adenocarcinoma of the colon or rectum
  • Head and neck squamous cell carcinoma (HNSCC) Cohort: Participants with histologically confirmed inoperable, locally advanced or metastatic, recurrent, or persistent HNSCC (oral cavity, oropharynx, hypopharnyx, or larynx) not amenable to curative therapy
  • 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 CIT (investigational or approved), including anti-PD−L1/PD-1 and/or anti-CTLA−4, 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 CIT (investigational or approved) including anti-PD−L1/PD-1
  • Renal cell carcinoma (RCC) Cohort: Participants with histologically confirmed incurable, advanced RCC with component of clear cell histology and/or component of sarcomatoid histology

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

  • Participants must have one of the following tumor types: NSCLC, UC, HNSCC, TNBC, RCC, melanoma, cervical cancer, anal cancer, Merkel-cell carcinoma, microsatellite instability (MSI)-High tumors, squamous cell carcinoma of the skin, hepatocellular carcinoma (non-viral), and CRC including microsatellite stable (MSS) and MSI-Low
  • 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

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 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 have elapsed between the last dose and the proposed Cycle 1, Day 1, with the exceptions as specified in protocol

Dose-Exploration/Expansion Cohorts in Phase 1b:

  • In the NSCLC CIT-Treated exploration cohort in Phase 1b, the most recent systemic treatment should have been anti-PD−L1/PD-1 as monotherapy or in combination
  • In the NSCLC CIT-Naïve expansion cohort in Phase 1b, prior treatment with immune checkpoint inhibitors (such as anti-PD−L1/PD-1), immunomodulatory mAbs, and/or mAb-derived therapies 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 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, or tuberculosis
  • 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
Information from the National Library of Medicine

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): NCT03289962


Contacts
Contact: Reference Study ID Number: GO39733 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 38 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Biontech RNA Pharmaceuticals GmbH
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03289962     History of Changes
Other Study ID Numbers: GO39733
2017-001475-23 ( EudraCT Number )
First Submitted: September 19, 2017
First Posted: September 21, 2017
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Breast Neoplasms