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

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

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 | 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

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. (PubMed, Nat Med) - P1 | "These findings support the continued development of autogene cevumeran in earlier treatment lines. ClinicalTrials.gov registration: NCT03289962 ."

IO biomarker • Journal • P1 data • Oncology • Solid Tumor • CD4 • CD8

BioNTech Provides Business and Pipeline Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Interim data from an ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran compared to watchful waiting in adjuvant ctDNA+ stage II (high risk) / stage III colorectal cancer ('CRC') are anticipated in late 2025 or 2026....Plan to present clinical data from an ongoing Phase 1/2a trial (NCT05150691) evaluating BNT323/DB-1303 in HER2-expressing advanced endometrial cancer in 2025. Preparation of a potential Biologics License Application ('BLA') submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer​ in 2025. Plan to initiate a global Phase 3 confirmatory clinical trial (NCT06340568) evaluating BNT323/DB-1303 in advanced endometrial cancer in 2025."

FDA filing • P1/2 data • P2 data • Trial status • Colorectal Cancer • Endometrial Cancer

At the Policlinico of Bari the first vaccine in the world to prevent recurrence of urinary tract cancer [Google translation] (la Repubblica) - "At the Policlinico di Bari, for the first time in the world, a patient affected by urinary tract cancer was started, after surgery, on the therapeutic combination of the personalized mRNA (messenger RNA) vaccine, autogenous cevumeran, and nivolumab immunotherapy (approved by international regulatory authorities, to date not yet reimbursed in Italy in this therapeutic scenario). This is a vaccine designed for the individual patient based on the specific mutations identified in their tumor sample. The patient is a 75-year-old woman, who last August underwent complete resection of a high-risk upper urinary tract cancer....The Policlinico di Bari was the first center among 110 worldwide, 9 of which in Italy, to effectively complete the screening phase of a patient eligible for the international clinical study evaluating the efficacy of the therapeutic combination of the cevumeran vaccine and the PD-1 inhibitor, nivolumab."

Reimbursement • Urethral 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 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

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

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 | Recruiting | Sponsor: BioNTech SE | N=229 ➔ 327 | Trial completion date: Jul 2027 ➔ Aug 2030 | Trial primary completion date: Feb 2026 ➔ Nov 2026

Circulating tumor DNA • Enrollment change • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

BioNTech Announces Third Quarter 2024 Financial Results and Corporate Update (BioNTech Press Release) - "A randomized, double-blind, multi-site Phase 2 clinical trial (IMCODE-004; NCT06534983) evaluating autogene cevumeran as an adjuvant treatment with nivolumab in patients with high-risk muscle-invasive urothelial cancer ('MIUC') is enrolling patients....BioNTech plans to disclose interim data from the Phase 2 clinical trial (NCT04486378) in stage II (high-risk) and III circulating tumor DNA+ ('ctDNA') adjuvant CRC, which is projected for late 2025 or 2026."

Enrollment status • P2 data • Colorectal Cancer • Gastrointestinal Cancer • 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: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • 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

Characterization of T cell responses induced by the individualized mRNA neoantigen vaccine autogene cevumeran in adjuvant stage II (high risk)/stage III colorectal cancer patients from the biomarker cohort of the phase 2 BNT122-01 trial. (ASCO 2024) - P2 | "Clinical Trial Registration Number: NCT04486378"

Biomarker • Clinical • P2 data • Tumor-specific neoantigens • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Characterization of T cell responses induced by the individualized mRNA neoantigen vaccine autogene cevumeran in adjuvant stage II (high risk)/stage III colorectal cancer (CRC) patients (pts) from the biomarker cohort of the phase II BNT122-01 trial (ESMO-GI 2024) - P2 | "In adjuvant CRC pts, autogene cevumeran induces poly-epitopic neoantigen-specific T-cell responses of high magnitude in all pts treated. Long-term immune response data will be presented."

Biomarker • Clinical • IO biomarker • P2 data • Tumor-specific neoantigens • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCR7 • CD8 • IFNG • PD-1

IMCODE004: 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • Urothelial Cancer

IMCODE004: 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 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Oncology • Solid Tumor • Urothelial Cancer

BioNTech Announces Second Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "A global, randomized Phase 2 clinical trial (NCT04534205) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma expressing PD-L1 is ongoing. Data updates are expected to be presented at the 2024 Congress of the European Society of Medical Oncology ('ESMO') taking place from September 13-17, 2024 in Barcelona, Spain....Preliminary data from the ongoing Phase 2 clinical trial (NCT04486378) in stage II (high risk) and III ctDNA+ adjuvant CRC is expected in late 2025 or 2026."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Preliminary results correlating post-operative ctDNA status with disease-free survival in patients with stage II (high risk)/III colorectal cancer in the BNT000-001 epidemiology study. (ASCO 2024) - P, P2 | "Other objectives include evaluation of the prognostic value of ctDNA and identification of ctDNA positive pts who might be candidates for the interventional clinical trial BNT122-01 (NCT04486378)... This study supports existing evidence of the prognostic value of post-operative ctDNA in CRC pts. In ctDNA positive pts, the 12-month DFS rate was almost halved (55% vs. 92% in ctDNA negative)."

Circulating tumor DNA • Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

BioNTech Announces First Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "Autogene cevumeran (BNT122) is a uridine mRNA-lipoplex based cancer vaccine candidate for individualized neoantigen-specific immunotherapy ('iNeST') being developed in collaboration with Genentech, Inc., a member of the Roche Group ('Genentech')....Epidemiologic data including post-operative circulating tumor DNA ('ctDNA') prevalence and prognostic value from a non-interventional, observational study (NCT04813627) in patients with resected high-risk stage II/III CRC are expected to be presented at the 2024 ASCO Annual Meeting. A Phase 2 clinical trial in an additional indication is planned. BNT211 consists of two investigational medicinal products...BioNTech plans to present an analysis of real world evidence investigating overall survival and treatment patterns of patients with testicular germ cell tumors receiving palliative chemotherapy at the 2024 ASCO Annual Meeting."

Observational data • Real-world evidence • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Testicular Cancer

IMCODE003: A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P2 | N=260 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: May 2029 ➔ Dec 2029 | Trial primary completion date: May 2029 ➔ Dec 2029

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

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

Three-year Phase 1 Follow-Up Data for mRNA-based Individualized Immunotherapy Candidate Show Persistence of Immune Response and Delayed Tumor Recurrence in Some Patients with Resected Pancreatic Cancer (GlobeNewswire) - P1 | N=29 | NCT04161755 | "In 8 of 16 patients, autogene cevumeran elicited high-magnitude T cells specific to the encoded neoantigens. 98% of the T cells targeting individual neoantigens on the tumor and induced by autogene cevumeran were de novo in that they were not detected in blood, tumors, and adjacent tissues prior to administration of the investigational treatment. Over 80% of the vaccine-induced neoantigen-specific T cells could still be detected up to three years post administration in patients with an immune response....6 of 8 patients with an immune response to autogene cevumeran remained disease free during the three-year follow-up period, while 7 of the 8 patients without an immune response to the treatment during the trial showed tumor recurrence."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor