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BRIEF TITLE: Safety and Pharmacokinetics of RO7198457 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Tumors

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


  • Org Study ID: GO39733
  • Secondary ID: 2017-001475-23
  • NCT ID: NCT03289962
  • NCT Alias:
  • Sponsor: Genentech, Inc. - Industry
  • Source: Genentech, Inc.

Brief Summary

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).

Overal Status Start Date Phase Study Type
Recruiting December 30, 2017 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)

Primary Outcome 1 - Time Frame: Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21

Primary Outcome 2 - Measure: MTD/Recommended Phase 2 Dose (RP2D) of RO7198457

Primary Outcome 2 - Time Frame: Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21

Primary Outcome 3 - Measure: 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

Primary Outcome 3 - Time Frame: Baseline up to end of the study (up to approximately 3 years)

Primary Outcome 4 - Measure: Percentage of Participants with Immune-Mediated Adverse Events (imAEs) by Severity According to NCI CTCAE Version 4.0

Primary Outcome 4 - Time Frame: Baseline up to end of the study (up to approximately 3 years)

Primary Outcome 5 - Measure: Percentage of Participants by Number of Treatment Cycles Received

Primary Outcome 5 - Time Frame: Baseline up to end of the study (up to approximately 3 years)

Primary Outcome 6 - Measure: Dose Intensity of RO7198457

Primary Outcome 6 - Time Frame: Baseline up to end of the study (up to approximately 3 years)

Condition:

  • Melanoma
  • Non-Small Cell Lung Cancer
  • Bladder Cancer
  • Colorectal Cancer
  • Triple Negative Breast Cancer
  • Renal Cancer
  • Head and Neck Cancer
  • Other Solid Cancers

Eligibility

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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Clinical Trials

Role: Study Director

Affiliation: Hoffmann-La Roche

Overall Contact

Name: Reference Study ID Number: GO39733 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. and Canada)

Email: global-roche-genentech-trials@gene.com

Locations

Facility Status Contact
HonorHealth Research Institute - Pima Center
Scottsdale, Arizona 85258
United States
Recruiting
The Angeles Clinic
Los Angeles, California 90025
United States
Recruiting
UCSF Comprehensive Cancer Ctr
San Francisco, California 94115
United States
Not yet recruiting
Stanford Cancer Center
Stanford, California 94305-5820
United States
Not yet recruiting
University of Colorado
Aurora, Colorado 80045-2517
United States
Recruiting
Yale University Cancer Center, Smilow Cancer Hospital; Medical Oncology
New Haven, Connecticut 06511
United States
Recruiting
Georgetown University
Washington, District of Columbia 20007
United States
Not yet recruiting
Massachusetts General Hospital.
Boston, Massachusetts 02114
United States
Not yet recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United States
Not yet recruiting
Dana Farber Can Ins
Boston, Massachusetts 02215
United States
Not yet recruiting
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
Las Vegas, Nevada 89169
United States
Recruiting
Columbia University Medical Center; Clinical Research Management Office
New York, New York 10032
United States
Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Not yet recruiting
Providence Oncology and Hematology Care Eastside
Portland, Oregon 97213
United States
Not yet recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15213
United States
Not yet recruiting
Sarah Cannon Res Inst; TN Onc
Nashville, Tennessee 37203
United States
Recruiting
Seattle Cancer Care Alliance
Seattle, Washington 98109
United States
Not yet recruiting
UZ Gent
Gent, 9000
Belgium
Not yet recruiting
CHU Sart-Tilman
Liège, 4000
Belgium
Not yet recruiting
Sint Augustinus Wilrijk
Wilrijk, 2610
Belgium
Not yet recruiting
The Ottawa Hospital Cancer Centre; Oncology
Ottawa, Ontario K1H 8L6
Canada
Not yet recruiting
Princess Margaret Cancer Center; Department of Radiation Oncology
Toronto, Ontario M5G 2M9
Canada
Not yet recruiting
Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
Essen, 45122
Germany
Not yet recruiting
LungenClinic Großhansdorf
Großhansdorf, 22927
Germany
Not yet recruiting
Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg
Heidelberg, 69120
Germany
Not yet recruiting
Fachklinik für Lungenerkrankungen
Immenhausen, 34376
Germany
Not yet recruiting
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, 55101
Germany
Not yet recruiting
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX
Netherlands
Not yet recruiting
LUMC
Leiden, 2300 ZA
Netherlands
Not yet recruiting
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX
Netherlands
Not yet recruiting
Clinica Universitaria de Navarra; Servicio de oncología
Pamplona, Navarra 31008
Spain
Not yet recruiting
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, 08035
Spain
Not yet recruiting
Karolinska Hospital; Oncology - Radiumhemmet
Stockholm, 17176
Sweden
Not yet recruiting
Akademiska sjukhuset, Onkologkliniken
Uppsala, 75185
Sweden
Not yet recruiting
Barts & London School of Med; Medical Oncology
London, EC1A 7BE
United Kingdom
Not yet recruiting
Southampton General Hospital; Medical Oncology
Southampton, SO16 6YD
United Kingdom
Not yet recruiting
The Royal Marsden Hospital
Sutton, SM2 5PT
United Kingdom
Not yet recruiting