A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants 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
2 other identifiers
interventional
272
8 countries
26
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 autogene cevumeran (RO7198457) as a single agent and in combination with atezolizumab (MPDL3280A, an engineered anti-programmed death-ligand 1 \[anti-PD-L1\] antibody).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2017
Longer than P75 for phase_1
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2017
CompletedFirst Posted
Study publicly available on registry
September 21, 2017
CompletedStudy Start
First participant enrolled
December 21, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2025
CompletedJuly 4, 2025
July 1, 2025
7.5 years
September 19, 2017
July 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21
MTD/Recommended Phase 2 Dose (RP2D) of Autogene Cevumeran
Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21
Percentage of Participants with Adverse Events (AEs)
Baseline up to end of the study (up to approximately 3 years)
Percentage of Participants with Immune-Mediated Adverse Events (imAEs)
Baseline up to end of the study (up to approximately 3 years)
Percentage of Participants by Number of Treatment Cycles Received
Baseline up to end of the study (up to approximately 3 years)
Dose Intensity of Autogene Cevumeran
Baseline up to end of the study (up to approximately 3 years)
Change from Baseline in Targeted Vital Signs
Baseline up to end of study (up to approximately 3 years)
Change from Baseline in Targeted Clinical Laboratory Test Results
Baseline up to end of study (up to approximately 3 years)
Change from Baseline in ECGs
Baseline up to end of study (up to approximately 3 years)
Secondary Outcomes (7)
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)
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
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
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
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
Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)
- +2 more secondary outcomes
Study Arms (5)
Phase 1a Flat Dose Escalation: Autogene Cevumeran
EXPERIMENTALParticipants will receive autogene cevumeran at escalated dosages.
Phase 1b Flat Dose Escalation: Autogene Cevumeran + Atezolizumab
EXPERIMENTALParticipants will receive autogene cevumeran at escalated dosages along with atezolizumab at a fixed dose of 1200 milligrams (mg)
Phase Ib: Dose Exploration: Autogene Cevumeran + Atezolizumab
EXPERIMENTALNon-small cell lung cancer (NSCLC) or melanoma cancer immunotherapy (CIT)-treated participants will receive autogene cevumeran (at dosage lower than maximum tolerated dose \[MTD\] based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
Phase 1b Expansion: Autogene Cevumeran + Atezolizumab
EXPERIMENTALParticipants with different indications as per inclusion criteria will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
Phase 1b Expansion: Autogene Cevumeran + Atezolizumab (Serial Biopsy)
EXPERIMENTALCIT-naive patients with selected tumor types who consent to optional serial biopsies will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a dixed dose of 1200 mg.
Interventions
Autogene cevumeran will be administered by intravenous (IV) infusion, in 21-day cycles.
Atezolizumab will be administered by IV infusion on Day 1 of every 21-day cycle.
Eligibility Criteria
You may qualify if:
- 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
- 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
- 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)
- +4 more criteria
You may not qualify if:
- 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 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)
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
- BioNTech SEcollaborator
Study Sites (26)
HonorHealth Research Institute ? Bisgrove
Scottsdale, Arizona, 85258, United States
UCSF Comprehensive Cancer Ctr
San Francisco, California, 94143, United States
Stanford Cancer Center
Stanford, California, 94305, United States
University of Colorado
Aurora, Colorado, 80045-2517, United States
Yale University Cancer Center, Smilow Cancer Hospital
New Haven, Connecticut, 06511, United States
Massachusetts General Hospital.
Boston, Massachusetts, 02114, United States
Dana Farber Can Ins
Boston, Massachusetts, 02215, United States
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
Las Vegas, Nevada, 89169, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Providence Oncology and Hematology Care Eastside
Portland, Oregon, 97213, United States
Sarah Cannon Res Inst
Nashville, Tennessee, 37203, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
UZ Gent
Ghent, 9000, Belgium
CHU de Liège (Sart Tilman)
Liège, 4000, Belgium
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
Fachklinik für Lungenerkrankungen
Immenhausen, 34376, Germany
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035, Spain
Akademiska sjukhuset, Onkologkliniken
Uppsala, 75185, Sweden
Barts & London School of Med
London, EC1A 7BE, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Related Publications (1)
Lopez J, Powles T, Braiteh F, Siu LL, LoRusso P, Friedman CF, Balmanoukian AS, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher GA, Schmidt M, Schuler M, Sullivan RJ, Burris HA, Galvao V, Henick BS, Dirix L, Jaeger D, Ott PA, Wong KM, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner RS, Rittmeyer A, Laurie SA, Gort E, Aljumaily R, Melero I, Sabado RL, Rhee I, Mancuso MR, Muller L, Fine GD, Yadav M, Kim L, Leveque VJP, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao GK, Low DW, Petry C, Lo AA, Schartner JM, Delamarre L, Mellman I, Lower M, Muller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lorks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kroner C, Tadmor AD, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn AN, Sahin U, Tureci O, Camidge DR. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nat Med. 2025 Jan;31(1):152-164. doi: 10.1038/s41591-024-03334-7. Epub 2025 Jan 6.
PMID: 39762422DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2017
First Posted
September 21, 2017
Study Start
December 21, 2017
Primary Completion
July 1, 2025
Study Completion
July 1, 2025
Last Updated
July 4, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share