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

Personalized neoantigen mRNA vaccines for pancreatic cancer: the role of lipid nanoparticle delivery systems. (PubMed, Daru) - "Personalized neoantigen mRNA vaccines delivered through LNPs represent a promising investigational strategy for PDAC. Further advances in neoantigen selection, mRNA engineering, LNP optimization, targeted delivery, and clinical evaluation are needed to establish their safety, efficacy, and therapeutic role."

Journal • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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

Translational Challenges and Opportunities in mRNA Cancer Vaccines. (PubMed, Cancer Discov) - "Messenger RNA (mRNA) cancer vaccines have progressed rapidly, with personalized platforms such as mRNA-4157 and BNT122 demonstrating feasibility, safety, and durable immune activity but limited scalability. Off-the-shelf constructs, including BNT111 and BNT113, enable faster, broader deployment, yet they risk reduced precision or immune tolerance...This mini-review synthesizes emerging clinical evidence and outlines strategies such as modular vaccine design, prime-boost vaccination regimens, and adaptive trial frameworks to reconcile these trade-offs and advance scalable, durable mRNA vaccines for broad oncologic impact. By dissecting the competing design pressures that shape mRNA vaccine performance, this mini-review proposes integrative strategies, spanning modular architectures, prime-boost regimens, and adaptive trials, to reconcile immunologic potency with manufacturability and safety, charting a roadmap toward next-generation cancer vaccines."

Journal • Review • Oncology

IMCODE003: A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC (clinicaltrials.gov) - P2 | N=260 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

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 Terminates Phase 2 Trial Of Autogene Cevumeran In Colorectal Cancer (RTTNews) - "The decision follows a recommendation from the independent Data Safety Monitoring Board (DSMB), which reviewed the latest available trial data and identified a numerical imbalance in overall survival between the treatment arms...The DSMB concluded that further continuation of the trial was unlikely to change the efficacy outcome and recommended discontinuing treatment and terminating the study...No new safety signals related to autogene cevumeran were identified, and the decision was not driven by safety concerns...The BNT122-01 trial was designed to evaluate whether individualized mRNA cancer immunotherapy alone could prevent disease recurrence in high-risk colorectal cancer patients compared with watchful waiting, the current standard of care....BioNTech said it will conduct a detailed analysis of the trial data to assess patient selection and inform the development strategy for potential future mRNA cancer immunotherapies."

DSMB • Trial termination • Colorectal Cancer

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=62 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • Urothelial Cancer

Personalized cancer vaccines: bridging immune-oncology and precision medicine for advanced therapeutics. (PubMed, Signal Transduct Target Ther) - "Despite advancements in therapeutic cancer vaccines, clinical translation has been hindered by limited efficacy, with Sipuleucel-T remaining the only FDA-approved therapeutic cancer vaccine to date. However, recent advances in personalized mRNA vaccines, such as Moderna's mRNA-4157 and BioNTech's autogene cevumeran, have demonstrated significant reductions in recurrence risk and improved survival across several cancer types, renewing optimism in the field...Increasing clinical evidence, especially in melanoma and pancreatic cancer, underscores the potential of these strategies to induce long-term protection and reduce recurrence. Overall, next-generation personalized cancer vaccines are advancing the transition from reactive treatment to proactive, precision-controlled cancer immunotherapy."

Journal • Review • Melanoma • Oncology • 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=62 | Recruiting | Sponsor: Hoffmann-La Roche | N=362 ➔ 62

Enrollment change • Oncology • Solid Tumor • Urothelial Cancer

Cancer vaccines: comprehensive review. (PubMed, BJS Open) - "Cancer vaccines are poised to complement surgery and systemic therapies, particularly in the perioperative window. Their integration into multimodal treatment strategies may redefine precision oncology, offering durable disease control and improved patient outcomes."

Journal • Review • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • TMB

BNT122-01: A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer (clinicaltrials.gov) - P2 | N=327 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

Circulating tumor DNA • Enrollment closed • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

mRNA vaccines in oncology: personalized cancer immunization and neoantigen targeting. (PubMed, Mol Cell Oncol) - "The mRNA-4157 (V940) combined with pembrolizumab demonstrated improved recurrence-free survival in resected high-risk melanoma patients (18-month RFS 79% vs 62%; HR 0.56). Similarly, the autogene cevumeran triggered significant neoantigen-specific T cell responses in 8 out of 16 patients with resected pancreatic ductal adenocarcinoma, leading to a delayed recurrence for immune responders (not reached vs 13.4 months; HR 0.08)...The review also addresses (i) clonality aware neoantigen selection; (ii) AI-based predictions of antigen presentation and immunogenicity, including issues of false positives; (iii) alternative delivery systems beyond lipid nanoparticles; and (iv) real-world challenges such as turnaround time, batch variability, regulatory frameworks, and operational costs that impact implementation. A structured model for crucial events and validation plans is proposed to bridge the gap between predictions and actual clinical benefits, utilizing techniques like..."

Journal • Review • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • 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 completion date: Jan 2034 ➔ Nov 2027 | Trial primary completion date: Mar 2029 ➔ Nov 2027

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

The building of a cancer vaccine trial platform: The NHS England Cancer Vaccine Launch Pad (CVLP) (AACR 2025) - P2 | "Sponsored by NHS England the first trial incorporated within the CVLP is BioNTech BNT122-01 (NCT04486378) investigating the RO7198457 mRNA vaccine in patients with ctDNA-positive, resected Stage II/III colorectal cancer. Between Sep 2023 and Dec 2024, 435 patients have consented to participate in the CVLP from 55 English sites, 96.4% of tissue samples were prepared in the required time frame for testing (average 2.5 days), of which 342 patients proceeded to referral to BNT122-01... CVLP has met its first feasibility endpoint of recruiting 300 patients and has progressed to onboarding further cancer vaccine trials."

Colorectal Cancer • Oncology • Solid Tumor

Personalized RNA neoantigen vaccines induce long-lived CD8+ T effector cells in pancreatic cancer (AACR 2024) - P1 | "Here, in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations, we discover that mRNA vaccines against mutation-derived neoantigens may solve this challenge.We recently reported (Rojas et al., Nature 2023) 1.5-yr median follow-up data (phase-I, NCT04161755) of sequential adjuvant atezolizumab (αPD-L1), autogene cevumeran (individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles), and mFOLFIRINOX in 16 surgically resected PDAC patients. In PDAC, autogene cevumeran induces polyfunctional CD8+ T effector cells of significant longevity, substantial magnitude, and durable function that correlate with delayed recurrence at sustained follow-up. mRNA may thus fulfill a pivotal requisite for effective cancer vaccines."

Tumor-specific neoantigens • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • IFNG • TNFA

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