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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001475-23 | EudraCT Number |
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| Name | Class |
|---|---|
| BioNTech SE | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1a Flat Dose Escalation: Autogene Cevumeran | Experimental | Participants will receive autogene cevumeran at escalated dosages. |
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| Phase 1b Flat Dose Escalation: Autogene Cevumeran + Atezolizumab | Experimental | Participants 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 | Experimental | Non-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. |
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| Phase 1b Expansion: Autogene Cevumeran + Atezolizumab | Experimental | Participants 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autogene cevumeran | Drug | Autogene cevumeran will be administered by intravenous (IV) infusion, in 21-day cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Cancer-Specific Inclusion Criteria:
Additional Inclusion Criteria for Participants in Each Indication-Specific Exploration/Expansion Cohort of Phase 1b:
Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of Phase 1b:
Exclusion Criteria:
All Cohorts (Dose-Escalation in Phase 1a and Dose-Escalation, Backfill, and Expansion in Phase 1b):
Treatment-Specific Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HonorHealth Research Institute ? Bisgrove | Scottsdale | Arizona | 85258 | United States | ||
| The Los Angeles Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39762422 | Derived | 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. |
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| Experimental |
CIT-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. |
|
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| Atezolizumab | Drug | Atezolizumab will be administered by IV infusion on Day 1 of every 21-day cycle. |
|
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| 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) |
| Overall Survival (OS) | 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 | Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years) |
| Los Angeles |
| California |
| 90025 |
| 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 |
| ZAS Sint Augustinus Wilrijk | Wilrijk | 2610 | Belgium |
| The Ottawa Hospital Cancer Centre | Ottawa | Ontario | K1H 8L6 | Canada |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 2M9 | Canada |
| Universitätsklinikum Essen | Essen | 45122 | Germany |
| Nationales Centrum für Tumorerkrankungen Heidelberg (NCT) | Heidelberg | 69120 | Germany |
| Fachklinik für Lungenerkrankungen | Immenhausen | 34376 | Germany |
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | 55101 | 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 |
| Karolinska Universitetssjukhuset, Solna | Stockholm | 751 85 | Sweden |
| Akademiska sjukhuset, Onkologkliniken | Uppsala | 75185 | Sweden |
| Barts Health NHS Trust - St Bartholomew's Hospital | London | EC1M 6BQ | United Kingdom |
| Southampton General Hospital | Southampton | SO16 6YD | United Kingdom |
| The Royal Marsden Hospital | Sutton | SM2 5PT | United Kingdom |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D001749 | Urinary Bladder Neoplasms |
| D015179 | Colorectal Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| D007680 | Kidney Neoplasms |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D001943 | Breast Neoplasms |
| D001941 | Breast Diseases |
| D007674 | Kidney Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
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