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 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

Reprogramming Immunosuppressive Niches and the Cancer Immunity Cycle in Pancreatic Cancer with Neoantigen mRNA Plus Immune Adjuvant Nanocarrier Strategies. (PubMed, ACS Nano) - "Clinically, the autogene cevumeran (BNT122) mRNA-lipoplex vaccine demonstrated that individualized neoantigen delivery can elicit durable, tissue-resident CD8+ T cells and prolong recurrence-free survival in resected PDAC, marking a breakthrough in restoring adaptive immunity to an otherwise "cold" tumor...Complementary silicasome platforms (lipid bilayer coated mesoporous silica nanoparticles) encapsulating irinotecan to induce immunogenic cell death (ICD) synergize with spleen-targeting LNPs carrying KRAS mRNA and TLR7/8 agonists, thereby bridging local antigen release with systemic T-cell priming. Together, these studies establish a translational framework wherein nanoparticle-based immunotherapy can both enhance and extend the benefits of mRNA vaccines from localized to metastatic PDAC. By integrating ICD induction, neoantigen targeting, and immune niche reprogramming, these modular nanomedicine platforms offer a realistic path toward scalable, durable, and..."

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

In October, data from a randomized Phase 2 clinical trial (IMCODE001; NCT03815058) evaluating the efficacy and safety of autogene cevumeran in combination with pembrolizumab versus pembrolizumab alone as a potential first-line treatment for patients with previously untreated advanced melanoma were presented at the 2025 ESMO Congress. (The Manila Times) - "While, as previously disclosed, the trial did not meet its primary efficacy endpoint of statically significant improvement of PFS in this advanced and aggressive tumor type, a numerical trend favoring the combination arm in overall survival ('OS') and PFS was observed, with the breadth of immune response correlating with a prolonged PFS in the combination arm. Autogene cevumeran induced and expanded high-magnitude and durable immune responses against the encoded neoantigens that persisted for up to 1.5 years after treatment completion."

P2 data • Melanoma

A randomized phase II study of autogene cevumeran plus pembrolizumab (pembro) versus pembro in 1L advanced melanoma (IMcode001) (ESMO 2025) - P2 | "Most evaluable patients showed neoantigen-specific immune responses, with broader responses trending toward improved PFS. Ongoing studies are assessing autogene cevumeran for the adjuvant treatment of resected pancreatic, urothelial, and colorectal cancers."

Clinical • IO biomarker • Metastases • P2 data • Tumor mutational burden • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CD8 • TMB

The NHS Cancer Vaccine Launch Pad (CVLP): A platform facilitating access to cancer vaccine clinical trials (ESMO 2025) - P2 | "The first clinical trial supported by the CVLP, is BNT122-01 (NCT04486378) investigating autogene cevumeran (BNT122, RO7198457), a personalised mRNA cancer vaccine candidate, in ctDNA-positive resected stage II/III colorectal cancer patients. Following proof of principle with one trial, the CVLP is expanding to support more trials including in melanoma and head and neck squamous cell carcinoma. Legal entity responsible for the study NHS England."

Clinical • Colorectal Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Dec 2029 ➔ Jan 2031 | Trial primary completion date: Dec 2029 ➔ Jan 2031

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

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 | Suspended ➔ Recruiting

Enrollment open • IO biomarker • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Cancer Vaccination and Immune-Based Approaches in Pancreatic Cancer. (PubMed, Cancers (Basel)) - "Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC."

IO biomarker • Journal • Review • 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 | Suspended | Sponsor: Hoffmann-La Roche | Recruiting ➔ Suspended

IO biomarker • Trial suspension • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

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 • HER2 Breast 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

A platform to identify patients for cancer vaccine trials: The NHS England Cancer Vaccine Launch Pad (CVLP). (ASCO 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 which reached approximately 60% of patients undergoing colorectal surgery via the CVLP from 55 sites across England. To facilitate screening to the cancer vaccine trial 96.4% of tissue samples were prepared in the required time frame for testing (average 2.5 days) providing proof of principal for this pathway and paving the way for the onboarding of further trials."

Clinical • Colorectal Cancer • Oncology • Solid Tumor

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

A randomised, double-blind Phase II study of autogene cevumeran + nivolumab (nivo) vs nivo as adjuvant therapy for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) (EAU 2025) - No abstract available

Clinical • P2 data • Oncology • Solid Tumor • Urothelial Cancer

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 Adenocarcinoma • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • HER2 Breast 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

Personalized medicine in pancreatic cancer: Harnessing the potential of mRNA vaccines. (PubMed, J Genet Eng Biotechnol) - "Emerging mRNA vaccines, such as autogene cevumeran (BNT122), show promise in enhancing treatment...Despite this progress, the complexity of PDAC remains a significant challenge. Continued research is essential to fully realize the potential of mRNA-based therapies in combating this deadly cancer."

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

BioNTech Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "First data from the ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran as an adjuvant treatment compared to watchful waiting after standard of care chemotherapy in resected circulating tumor DNA+ ('ctDNA') stage II (high-risk) and III colorectal cancer ('CRC') are anticipated in late 2025 or early 2026. BNT111 is based on BioNTech’s fully owned, off-the-shelf FixVac platform, and encodes four melanoma-associated antigens. BioNTech plans to present data from the ongoing Phase 2 clinical trial (BNT111-01; NCT04526899) at a medical conference in 2025."

P2 data • Colorectal Cancer • Melanoma

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 | Initiation date: Jul 2024 ➔ Dec 2024

Trial initiation date • Oncology • Solid Tumor • Urothelial Cancer

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