BNT116 / BioNTech - LARVOL DELTA

Phase I trial evaluating BNT116, a TAA-encoding mRNA vaccine, in combination with cemiplimab in frail patients with advanced non-small cell lung cancer (NSCLC) (AACR 2025) - "BNT116 plus cemiplimab demonstrated promising anti-tumor activity, consistent immune response induction, and a manageable safety profile in frail pts with advanced NSCLC. Updated safety and clinical activity data will be presented along with biomarker data."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CLDN6 • IFNG • MAGEA4 • MAGEC1 • PRAME

BioNTech will present data from the Phase 1 clinical trial LuCa-MERIT-1 (GlobeNewswire) - P1 | N=160 | LuCa-MERIT-1 (NCT05142189) | Sponsor: BioNTech SE | "The update includes safety and clinical activity data, along with biomarker data from a cohort of frail patients with advanced or metastatic non-small cell lung cancer ('NSCLC') who were not eligible for platinum-based chemotherapy as first-line treatment. The preliminary data showed anti-tumor activity, consistent immune response induction, and a manageable safety profile."

P1 data • Non Small Cell Lung Cancer

Groundbreaking mRNA Lung Cancer Vaccine Trials: A New Dawn in Cancer Treatment. (PubMed, Curr Cancer Drug Targets) - P1 | "Success in the BNT116 trials could redefine NSCLC treatment paradigms, offering a targeted, less cytotoxic alternative. This innovation can not only improve therapeutic outcomes, but also pave the way for preven-tive cancer vaccines, signaling a new dawn in cancer treatment."

Journal • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Solid Tumor

Preliminary results from LuCa-MERIT-1, a phase I trial evaluating BNT116, a fixed antigen mRNA vaccine, plus cemiplimab in advanced non-small cell lung cancer after progression on PD-1 inhibition (SITC 2024) - P1 | "In conclusion, the response profile suggests BNT116+cemiplimab may induce reversion of resistance to PD-1 inhibition in NSCLC. Ethics Approval This trial received relevant Ethics & Institutional Review Board approvals in participating countries prior to initiation.View this table:View inline View popup Download powerpoint Abstract 1486 Table 1 Baseline characteristics of LuCa-MERIT-1 patients treated with BNT116+cemiplimab"

IO biomarker • Late-breaking abstract • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Aug 2027 ➔ Nov 2028 | Trial primary completion date: Jan 2026 ➔ Apr 2027

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Identification of Candidate Therapeutic Targets Using Single Cell RNA Sequencing in ALK-Positive Lung Cancers (IASLC-WCLC 2024) - "Second, we found support for clinical trials of solid tumor vaccines like BNT116 for ALK+ and EGFR+ LC patients because 70% of ALK+ patients and 59% of EGFR+ patients sampled express one or more among the six proteins in this mRNA vaccine...Conclusions : Taken together, we believe these types of data offer opportunities to expedite therapeutic development of improved treatments for ALK+ and other oncogene-driven LC patients. We will extend this work to include validation of transcriptome-nominated targets in tumor cells using immunohistochemistry, mass spectrometry and other protein expression assays, and in vitro and in vivo models."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ALK • EGFR

First UK patient receives innovative lung cancer vaccine (UCLH NHS) - "A lung cancer patient at UCLH is the first to receive a novel cancer vaccine designed to prime the immune system to recognise and fight cancer cells...The primary objective of this study is to determine if BNT116 is safe and well tolerated. The trial will be enrolling patients at different stages of NSCLC, from early-stage NSCLC before surgery or radiotherapy (Stage 2 and 3) to late-stage disease (Stage 4) or recurrent cancer...The trial aims to establish the safety profile and a safe dose of BNT116 monotherapy, as well as of BNT116 in combination with established treatments for NSCLC to see if BNT116 has a synergistic anti-tumour effect when given with these established chemotherapy or immunotherapy treatments....Approximately 130 participants will be enrolled in the study across 34 research sites in seven countries, with six UK sites selected."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BNT116: “Preliminary results of BNT116 show encouraging antitumor activity and manageable safety profile in combination with docetaxel”; Non-small cell lung cancer (BioNTech) - Q1 2024 Results

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

BioNTech Announces First Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - P1 | N=130 | LuCa-MERIT-1 (NCT05142189) | Sponsor: BioNTech SE | "In April 2024, data from a Phase 1 trial cohort (NCT05142189) were presented at the AACR Annual Meeting. Patients were treated with BNT116 in combination with docetaxel after progression on a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Preliminary data of BNT116 in combination with docetaxel show encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Efficacy results suggest that combination therapy with BNT116 and docetaxel was active with an overall response rate ('ORR') of 30% and a disease control rate ('DCR') of 85%."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer (AACR 2024) - "BNT116 + DTX shows encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Updated safety and clinical activity data will be presented along with additional biomarker data."

Clinical • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CLDN6 • MAGEA4 • PRAME

BioNTech to Present Clinical Data Updates for Personalized mRNA-based and Targeted Oncology Candidates at AACR 2024 (GlobeNewswire) - "Highlights of BioNTech’s clinical stage programs to be presented at AACR Annual Meeting 2024: Longer-term follow-up data of activity and immune responses of the investigator-initiated first-in-human Phase 1 trial (NCT04161755) with the mRNA-based individualized neoantigen-specific immunotherapy ('iNeST') candidate autogene cevumeran (BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma ('PDAC') will be presented....BioNTech will present preliminary results on the LuCa-MERIT-1 Phase 1 trial (NCT05142189) with its off-the-shelf, shared tumor-associated-antigen-based mRNA therapeutic cancer vaccine candidate BNT116 in combination with docetaxel in patients with advanced unresectable or metastatic non-small cell lung cancer ('NSCLC')."

P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: BioNTech SE

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen RNA vaccine BNT116 in patients with advanced non-small cell lung cancer (SITC 2023) - "Methods LuCa-MERIT-1 is a first-in-human, open label, Phase I trial with cohorts to confirm the dose of BNT116 alone or as combination therapy with cemiplimab, docetaxel, and/or carboplatin/paclitaxel (21-day cycles). Conclusions In this trial, BNT116 was generally well tolerated with an expected safety profile as monotherapy and in combination with cemiplimab. Updated safety and clinical activity data will be presented along with additional biomarker data (TAA expression, PD-L1 expression, cytokines, tumor markers)."

Clinical • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BioNTech to Present Multiple Program Updates Across Modalities at ESMO Congress 2023 (GlobeNewswire) - P1/2 | N=235 | NCT05438329 | Sponsor: DualityBio Inc. | "The Company will present first-in-human data of BNT325 (DB-1305) (NCT05438329), a next-generation Trop-2-targeting antibody-drug conjugate ('ADC')...Initial data with this candidate show encouraging preliminary efficacy and a manageable safety profile in patients with advanced/metastatic non-small cell lung cancer (NSCLC)....A trial in progress poster will inform on the ongoing EMPOWERVAX Lung 1 Phase 2 trial (NCT05557591)...evaluating the efficacy and safety of BioNTech’s fully-owned off-the-shelf mRNA cancer vaccine candidate BNT116 in combination with cemiplimab versus cemiplimab alone in the first-line treatment of patients with advanced NSCLC and PD-L1 expression ≥50%."

P1/2 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BioNTech to Present Clinical and Preclinical Data Updates Across Multiple Immuno-Oncology Programs at 2023 SITC Annual Meeting (BioNTech Press Release) - P1 | N=130 | LuCa-MERIT-1 (NCT05142189) | Sponsor: BioNTech SE | "First clinical data will be presented on the LuCa-MERIT-1 Phase 1 study (NCT05142189) with BioNTech’s off-the-shelf mRNA therapeutic cancer vaccine candidate BNT116 alone and in combination with cemiplimab in patients with advanced, unresectable, or metastatic NSCLC. The data show encouraging initial clinical activity in heavily pre-treated patients with advanced NSCLC and a tolerable safety profile."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase II study of cemiplimab plus BNT116 versus cemiplimab alone in first-line treatment of patients with advanced non-small cell lung cancer with PD-L1 expression ≥50% (ESMO 2023) - P2 | "Enrollment of up to 100 patients is planned. Enrolment is ongoing."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: BioNTech SE | N=80 ➔ 130 | Trial primary completion date: May 2025 ➔ Jan 2026

Enrollment change • Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety and Efficacy of Intravenous Cemiplimab Plus BNT116 Versus Cemiplimab Alone in Advanced Non-Small Cell Lung Cancer in Adult Participants With PD-L1 ≥ 50% (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting | Phase classification: P1/2 ➔ P2

Combination therapy • Enrollment open • Metastases • Monotherapy • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Safety and Efficacy of Intravenous Cemiplimab Plus BNT116 Versus Cemiplimab Alone in Advanced Non-Small Cell Lung Cancer in Adult Participants With PD-L1 ≥ 50% (clinicaltrials.gov) - P1/2 | N=107 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Sep 2027 ➔ Jun 2027 | Trial primary completion date: Jun 2027 ➔ Mar 2027

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

LuCa-MERIT-1: First-in-human, open label, phase I dose confirmation trial evaluating the safety, tolerability, and preliminary efficacy of BNT116 alone and in combinations in patients with advanced non-small cell lung cancer (ESMO 2022) - P1 | "BNT116 alone or in combination with either docetaxel or the PD-1 inhibitor cemiplimab (Libtayo®) may have synergistic anti-tumor effects, thus potentially addressing the unmet medical need of these cancer patients. Secondary endpoints are related to clinical activity, i.e., tumor assessments, as per RECIST 1.1. The first patient is planned to be dosed in May 2022, with enrolment expected for approximately 12 months."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

LuCa-MERIT-1: First-in-human open label dose confirmation trial evaluating safety, tolerability, and efficacy of BNT116 alone and in combinations in patients with advanced non-small cell lung cancer (SITC 2022) - "BNT116 alone or in combination with either docetaxel or the PD-1 inhibitor cemiplimab (Libtayo ® ) may have synergistic anti-tumor effects, thus potentially addressing the unmet medical need of these cancer patients. The first patient was dosed in JUL 2022, with enrolment expected for approximately 12 months. The study was approved by IRB/IEC, approval numbers: 2022-03/1691 (Turkey), OGYÉI/6962-9/2022 (Hungary), and US and Spain (approval numbers for the later were not provided)."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BioNTech Announces Third Quarter 2022 Financial Results and Corporate Update (GlobeNewswire) - "BioNTech expects continued pipeline advancement and expansion as well as one more data readout from an ongoing trial for the remainder of 2022. In 2023, BioNTech expects to provide up to ten clinical trial updates in oncology....A second trial evaluates BNT116 alone and in combination with cemiplimab as first-line treatment of patients with advanced NSCLC whose tumors express programmed cell death ligand-1 (PD-L1) in ≥ 50% of tumor cells...The trial is expected to dose the first patient in the fourth quarter of 2022 and is sponsored by Regeneron Pharmaceuticals, Inc....A Phase 1/2 trial in patients with solid tumors is ongoing. Expansion cohorts in melanoma, NSCLC, pancreatic and head and neck carcinoma are recruiting for combination regimens of BNT312 in these indications. Safety and preliminary efficacy data of BNT312 combination therapy in patients with advanced solid tumors are planned to be presented at the ESMO-Immuno-Oncology annual congress in December 2022."

P1/2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Safety and Efficacy of Intravenous Cemiplimab Plus BNT116 Versus Cemiplimab Alone in Advanced Non-Small Cell Lung Cancer in Adult Participants With PD-L1 ≥ 50% (clinicaltrials.gov) - P1/2 | N=107 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

Combination therapy • Monotherapy • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Patients with Chronic Lymphocytic Leukemia Have a Very High Risk of Ineffective Response to the BNT162b2 Vaccine. (PubMed, Vaccines (Basel)) - "We conducted a single-center study with the main objective to evaluate the immunogenicity of the BNT1162b2 mRNA vaccines in 42 patients affected by CLL with the assessment of antibody response after the second and the third dose. Our data, despite the small size of our cohort, demonstrate that patients with CLL have a low rate of effective response to the BNT162b2 vaccine. However, the effective role of a subsequent dose is still unclear, highlighting the need for alternative methods of immunization in this particularly fragile group of patients."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor