GEN1053 / Genmab, BioNTech - LARVOL DELTA

A hexamerization-enhanced, Fc-silenced agonistic CD27 antibody amplifies T-cell effector functions as single agent and in combination with PD-1 blockade. (PubMed, Sci Rep) - "HexaBody-CD27 (GEN1053/BNT313) is an investigational novel agonistic CD27 antibody engineered to enhance T-cell costimulation and promote antitumor immunity...In conclusion, HexaBody-CD27 enhanced T-cell activation and effector functions in an FcγR-crosslinking-independent manner, without inducing T-cell depletion. The immune agonist activity of HexaBody-CD27 was potentiated in combination with PD-1 blockade."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD27 • CD8

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy (clinicaltrials.gov) - P1/2 | N=31 | Terminated | Sponsor: Genmab | N=103 ➔ 31 | Trial completion date: Dec 2026 ➔ May 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ May 2024; Due to strategic evaluation of GEN1053 within the context of Genmab's portfolio

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Combination of HexaBody-CD27 with PD-(L)1 blockade potentiates single-agent activity leading to enhanced human T-cell effector functions in vitro (CIMT 2024) - P1/2 | "HexaBody®-CD27 (GEN1053/BNT313) is a novel CD27 human monoclonal antibody with a functionally inert IgG1 Fc domain harboring a hexamerization- enhancing mutation to induce CD27 activation independently of Fc gamma receptor crosslinking, while also avoiding T-cell depletion...Here we present preclinical studies investigating the effect of combining HexaBody-CD27 with anti-PD(L)1 antibodies (pembrolizumab, nivolumab, and atezolizumab) on human T cells [1]...These findings provide preclinical rationale for investigation of this combination in clinical trials. The clinical safety and preliminary antitumor activity of HexaBody-CD27 is currently being evaluated in patients with advanced solid tumors (NCT05435339)."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD27 • CD8 • CLDN6 • GZMB • IFNG • LAMP1

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy (clinicaltrials.gov) - P1/2 | N=103 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2027 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Sep 2026

Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Combination of HexaBody-CD27 with PD-(L)1 blockade potentiates single-agent activity leading to enhanced human T-cell effector functions in vitro (SITC 2023) - P1/2 | "HexaBody®-CD27 (GEN1053/BNT313) is a novel CD27 human monoclonal antibody with a functionally inert IgG1 Fc domain harboring a hexamerization-enhancing mutation to induce CD27 activation independently of Fc gamma receptor crosslinking, while also avoiding T-cell depletion...Methods The effects of combining HexaBody-CD27 with anti-PD-(L)1 antibodies (pembrolizumab, nivolumab, and atezolizumab) on human CD8+ T-cell proliferation and effector functions were investigated in vitro...This study provides preclinical rationale for investigation of this combination in clinical trials. HexaBody-CD27 is currently being evaluated in patients with advanced solid tumors (NCT05435339)."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD27 • CD8 • CLDN6 • GZMB • IFNG • LAMP1

HexaBody-CD27 enhances T-cell activation, proliferation, cytokine secretion and cytotoxic activity independently of Fc gamma receptor-mediated crosslinking (SITC 2022) - P1/2 | "HexaBody-CD27 (GEN1053/BNT313) is a novel anti-CD27 mAb with an IgG Fc domain engineered to induce CD27 agonist activity independently of FcγR-bearing cells, which may be scarce in tumors...in China. Animals were housed and handled in accordance with good animal practice as defined by the regulations of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD27 • CD4 • CD8 • IFNG

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy (clinicaltrials.gov) - P1/2 | N=103 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy and in Combination Estudio para evaluar la seguridad, la tolerabilidad y el efecto preliminar del anticuerpo GEN1053 en tumores sólidos malignos como monoterapia y en combinación (clinicaltrialsregister.eu) - P1/2 | N=170 | Ongoing | Sponsor: Genmab B.V.

Combination therapy • Monotherapy • New P1/2 trial • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

BioNTech Announces Second Quarter Financial Results and Corporate Update (GlobeNewswire) - "A data update from the ongoing randomized Phase 2 trial of autogene cevumeran combined with pembrolizumab in patients with first-line metastatic melanoma is now expected in the first half of 2023; BNT313 (GEN1053) – A Phase 1 trial to evaluate the safety, tolerability, and preliminary efficacy of BNT313 on malignant solid tumors as monotherapy is expected to be initiated in the second half of 2022."

P1 data • P2 data • Melanoma • Oncology • Solid Tumor

Genmab and BioNTech Expand Global Strategic Collaboration to Develop and Commercialize Novel Immunotherapy Candidates (GlobeNewswire) - "Genmab...and BioNTech SE...announced an expansion of their global strategic collaboration to develop and commercialize novel immunotherapies for the treatment of cancer patients. Under the expansion, Genmab and BioNTech will jointly work to research, develop, and commercialize novel monospecific antibody candidates for various cancer indications....Under the expanded collaboration, the companies will jointly develop and commercialize, subject to regulatory approval, monospecific antibodies leveraging Genmab’s proprietary HexaBody® technology platform. The first monospecific antibody candidate, GEN1053/BNT313, is expected to enter clinical trials by the end of 2022.... Under the terms of the agreement, the companies will equally share the development costs and potential future profit deriving from GEN1053/BNT313."

Licensing / partnership • New P1/2 trial • Oncology • Solid Tumor

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy (clinicaltrials.gov) - P1/2 | N=103 | Not yet recruiting | Sponsor: Genmab

Monotherapy • New P1/2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck