Bladder Cancer, Colorectal Cancer, Head and Neck Cancer, Melanoma, Non-Small Cell Lung Cancer, Other Solid Cancers, Renal Cancer, Triple Negative Breast Cancer
Conditions
Keywords
Neoantigen, Personalized, Atezolizumab, Immunotherapy, Anti-PDL1, Checkpoint Inhibitor
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).
Interventions
Autogene cevumeran will be administered by intravenous (IV) infusion, in 21-day cycles.
DRUGAtezolizumab
Atezolizumab will be administered by IV infusion on Day 1 of every 21-day cycle.
Sponsors
Genentech, Inc.
BioNTech SE
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
* 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
Design outcomes
Primary
| Measure | 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) |
Secondary
| Measure | 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 | 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) |
Countries
Belgium, Canada, Germany, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed