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

Program Status

Active, not recruiting

Phase

Phase 1

Prior Immunotherapy Allowed

Yes

CRC-directed Trial

Yes

Drugs

Atezolizumab, Autogene cevumeran, Tecentriq

Tags

MSS/ MMRp

Comments

Therapeutic personalized vaccine + anti PD-L1 (Atezolizumab, Tecentriq)
Recruiting patients with advanced cancer; important size of the trial (572 patients), recruiting multiple cancer types including MSS and MSI-high CRC in many locations.
Patients only need to have progressed after at least one available standard therapy; i.e., no need of having exhausted standard of care.
Prior Prior checkpoint inhibitor allowed.
It has been reported by patients that for this vaccine trial you must have your spleen.
RO7198457 is developed by Roche using BioNTech’s Individualized Vaccines Against Cancer (IVAC®) MUTANOME clinical platform.
IVAC® MUTANOME, then, is an individualized RNA vaccine based on targeting individual mutant neoantigens/ patient-specific mutations.

Location Location Status
United States
HonorHealth Research Institute ? Bisgrove
Scottsdale, Arizona 85258
Active, not recruiting
The Los Angeles Clinic
Los Angeles, California 90025
Active, not recruiting
UCSF Comprehensive Cancer Ctr
San Francisco, California 94143
Active, not recruiting
Stanford Cancer Center
Stanford, California 94305
Active, not recruiting
University of Colorado
Aurora, Colorado 80045-2517
Active, not recruiting
Yale University Cancer Center, Smilow Cancer Hospital
New Haven, Connecticut 06511
Active, not recruiting
Massachusetts General Hospital.
Boston, Massachusetts 02114
Active, not recruiting
Dana Farber Can Ins
Boston, Massachusetts 02215
Active, not recruiting
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
Las Vegas, Nevada 89169
Active, not recruiting
Columbia University Medical Center
New York, New York 10032
Active, not recruiting
Memorial Sloan Kettering Cancer Center
New York, New York 10065
Active, not recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Active, not recruiting
Providence Oncology and Hematology Care Eastside
Portland, Oregon 97213
Active, not recruiting
Sarah Cannon Res Inst
Nashville, Tennessee 37203
Active, not recruiting
Seattle Cancer Care Alliance
Seattle, Washington 98109
Active, not recruiting
Belgium
UZ Gent
Gent 9000
Active, not recruiting
CHU Sart-Tilman
Liège 4000
Active, not recruiting
Sint Augustinus Wilrijk
Wilrijk 2610
Active, not recruiting
Canada
The Ottawa Hospital Cancer Centre
Ottawa, Ontario K1H 8L6
Active, not recruiting
Princess Margaret Cancer Center
Toronto, Ontario M5G 2M9
Active, not recruiting
Germany
Universitätsklinikum Essen
Essen 45122
Active, not recruiting
Nationales Centrum für Tumorerkrankungen Heidelberg (NCT)
Heidelberg 69120
Active, not recruiting
Fachklinik für Lungenerkrankungen
Immenhausen 34376
Active, not recruiting
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz 55101
Active, not recruiting
Netherlands
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam 1066 CX
Active, not recruiting
Universitair Medisch Centrum Utrecht
Utrecht 3584 CX
Active, not recruiting
Spain
Clinica Universitaria de Navarra
Pamplona, Navarra 31008
Active, not recruiting
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona 08035
Active, not recruiting
Sweden
Karolinska Hospital
Stockholm 17176
Active, not recruiting
Akademiska sjukhuset, Onkologkliniken
Uppsala 75185
Active, not recruiting
United Kingdom
Barts & London School of Med
London EC1A 7BE
Active, not recruiting
Southampton General Hospital
Southampton SO16 6YD
Active, not recruiting
The Royal Marsden Hospital
Sutton SM2 5PT
Active, not recruiting

Inclusion 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 in Each Indication-Specific Exploration/Expansion Cohort of Phase 1b:

* NSCLC Cohorts (CIT-Naive): 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-Naive): 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-Naive): 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-Naive): 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-Naive): 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-Naive): 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-Naive 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/ or PD-1 with or without 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

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 non-melanoma CIT-Naive 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-naive in metastatic setting expansion cohort in Phase Ib, prior treatment with anti-PD- L1/PD-1 and/or anti-CTLA-4 (investigational or approved) is not allowed. Prior anti-PD-L1/PD-1 and/or anti-CTLA-4 therapy in the adjuvant setting is allowed provided that there is at least a 6-month treatment-free interval between completion of adjuvant therapy and Cycle 1, Day 1.
* 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-mediated 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-mediated 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 =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

NCT ID

NCT03289962

Date Trial Added

2017-09-21

Updated Date

2025-01-17