autogene cevumeran (RG6180) / Roche, BioNTech - LARVOL DELTA

RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. (PubMed, Nature) - "At an extended 3.2-year median follow-up from a phase 1 trial of surgery, atezolizumab (PD-L1 inhibitory antibody), autogene cevumeran1 (individualized neoantigen vaccine with backbone-optimized uridine mRNA-lipoplex nanoparticles) and modified (m) FOLFIRINOX (chemotherapy) in patients with PDAC, we find that responders with vaccine-induced T cells (n = 8) have prolonged recurrence-free survival (RFS; median not reached) compared with non-responders without vaccine-induced T cells (n = 8; median RFS 13.4 months; P  =  0.007)...Thus, in PDAC, autogene cevumeran induces de novo CD8+ T cells with multiyear longevity, substantial magnitude and durable effector functions that may delay PDAC recurrence. Adjuvant mRNA-lipoplex neoantigen vaccines may thus solve a pivotal obstacle for cancer vaccination."

IO biomarker • Journal • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8

IMCODE001: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Sep 2022 ➔ Apr 2024 | Trial primary completion date: Sep 2022 ➔ Apr 2024

Trial completion date • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

IMCODE001: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (clinicaltrials.gov) - P2 | N=132 | Recruiting | Sponsor: Genentech, Inc.

New P2 trial • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

IMCODE001: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Jun 2024 ➔ Oct 2025 | Trial primary completion date: Jun 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

IMCODE001: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (clinicaltrials.gov) - P2 | N=131 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jan 2025 | Trial primary completion date: Oct 2025 ➔ Jan 2025

Trial completion • Trial completion date • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

IMCODE001: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma. (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Jun 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1 | N=272 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Feb 2024 ➔ Jun 2023 | Trial primary completion date: Feb 2024 ➔ Jun 2023

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1 | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=572 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Melanoma • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Sep 2023 ➔ Nov 2024 | Trial primary completion date: Sep 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=572 | Not yet recruiting | Sponsor: Genentech, Inc.

New P1 trial • Bladder Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Melanoma • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting | N=770 ➔ 272

Enrollment change • Enrollment closed • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=770 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Oct 2020 ➔ Feb 2024 | Trial primary completion date: Sep 2020 ➔ Feb 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1 | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Phase classification: P1a/1b ➔ P1

Phase classification • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1 | N=272 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

GO39733: A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov) - P1a/1b | N=770 | Recruiting | Sponsor: Genentech, Inc. | N=567 ➔ 770

Enrollment change • Bladder Cancer • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • ER • HER-2 • PGR

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. (PubMed, Nature) - "After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence."

IO biomarker • Journal • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatology • Infectious Disease • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Respiratory Diseases • Solid Tumor • CD8

Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma. (ASCO 2022) - P1 | " n=19 patients underwent surgery and received atezolizumab at 6.3 weeks (median; 95% CI 6.0–6.57) after surgery with no ≥ grade 3 (Gr3) adverse events... Autogene cevumeran is safe, feasibly manufactured in a clinically relevant timeframe, and immunogenic in PDAC. Vaccine induced neoantigen-specific immunity preliminarily correlates with improved PDAC outcome. Further clinical trials in PDAC are warranted."

Clinical • IO biomarker • P1 data • Tumor-specific neoantigens • Hypertension • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8 • IFNG

BioNTech Provides Strategic Business Update and Outlines 2026 Areas of Focus at 44th Annual J.P. Morgan Healthcare Conference (The Manila Times) - "Expected 2026 oncology milestones include seven late-stage data readouts...Additional late-stage trial readouts through 2030+ set to create multiple launch opportunities across tumor types, building BioNTech into a multi-product oncology company."

Clinical data • New P3 trial • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Study of Personalized Tumor Vaccines (PCVs) and a PD-L1 Blocker in Patients With Pancreatic Cancer That Can be Treated With Surgery (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

IMCODE-004: A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran With Nivolumab Versus Nivolumab Alone in Participants With High-risk Muscle-invasive Urothelial Carcinoma (MIUC) (clinicaltrials.gov) - P2 | N=362 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Nov 2028 ➔ Mar 2029

IO biomarker • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics. (PubMed, Cancer Innov) - "Clinically, more than 150 trials have demonstrated the synergistic efficacy of mRNA vaccines (e.g., mRNA-4157/V940, BNT122) in combination with immune checkpoint inhibitors (ICIs), particularly in melanoma, with Phase III trials currently underway. Future research directions encompass self-amplifying mRNA constructs, novel biomaterial vectors, neoadjuvant applications, and multi-omics integration for next-generation vaccine development. With rapid industrialization and evolving regulatory frameworks, mRNA vaccines are well-positioned to revolutionize precision cancer immunotherapy despite persistent translational barriers."

IO biomarker • Journal • Review • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor

Cancer vaccines: advances, hurdles, and future directions. (PubMed, Explor Target Antitumor Ther) - "We explore cutting-edge clinical data, including long-lived T-cell memory and promising outcomes in various cancer types, including pancreatic ductal adenocarcinoma (PDAC), melanoma, head and neck cancers, renal cell carcinoma (RCC), and others. We address critical challenges, including tumor heterogeneity, manufacturing scalability, biomarker development, and regulatory frameworks, and propose an integrated translational ecosystem to accelerate the adoption of personalized cancer vaccines."

Journal • Review • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor