tecaginlimab (GEN1042) / Genmab, BioNTech - LARVOL DELTA

GCT1042-01: GEN1042 Safety Trial and Anti-tumor Activity in Participants with Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=1287 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Genmab | N=30 ➔ 42 | Trial primary completion date: Jul 2026 ➔ Mar 2026

Enrollment change • Monotherapy • Trial primary completion date • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=88 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • CNS Tumor • Oncology • Solid Tumor

A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Genmab | Trial completion date: Oct 2027 ➔ Feb 2027

Combination therapy • Monotherapy • Trial completion date • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Finanshus after accounting from Johnson & Johnson: The focus is on upcoming updates from Genmab's pipeline [Google translation] (MedWatch) - "Jefferies analyst Peter Welford notes that Johnson & Johnson reported second-quarter Darzalex sales of $2.88 billion. dollar is 3-4 per cent. above the consensus estimates and Jefferies' own estimate...But in relation to the share price for Genmab, it is more the company's development pipeline that is in focus, Welford assesses...'In the short term, the focus is on Epkinly (Genmab's cancer drug, ed) maintaining its launch course in the US, updated Acasunlimab lung cancer data at the WCLC lung cancer conference and the first 1042 results.'....The results will probably be available at a scientific meeting in the fourth quarter, Jefferies estimates."

Clinical data • Sales • Follicular Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies. (PubMed, Cancer Treat Rev) - "ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting."

Journal • Review • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Pneumonia • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

GEN1042-mIgG2a, an Fc-inert mouse-human chimeric variant of GEN1042 (DuoBody®-CD40x4-1BB), exhibits in vivo antitumor activity and peripheral immune modulation (CIMT 2024) - P1/2 | "This model has enabled ongoing preclinical exploration of GEN1042 in combination with PD-1 blockade and a platinum-based chemotherapy doublet, which is hypothesized to potentiate antitumor activity through complementary immune modulatory effects. These data support ongoing clinical studies evaluating combination therapy in patients with advanced solid tumors (NCT04083599, NCT05491317)."

IO biomarker • Preclinical • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • CD40 • CD86 • IFNG

BioNTech Announces Fourth Quarter and Full Year 2023 Financial Results and Corporate Update (GlobeNewswire) - "BNT312/GEN1042:...The companies intend to share updated data at a medical conference in the second half of 2024 from an ongoing Phase 1/2 dose-escalation clinical trial (NCT04083599) with expansion cohorts evaluating safety and anti-tumor activity of BNT312/GEN1042 as monotherapy and in combination therapies in patients with solid tumors."

P1/2 data • Solid Tumor

GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=1287 | Recruiting | Sponsor: Genmab | N=647 ➔ 1287 | Trial primary completion date: Oct 2025 ➔ Jul 2025

Enrollment change • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Safety and Antitumor Activity of GEN1042 in Combination with Pembrolizumab _ Chemotherapy in Solid Tumors: Phase 2b Dose-Expansion Trial in Progress (ESMO-IO 2023) - P1/2 | "Eligible patients with recurrent/metastatic HNSCC (PD-L1 combined positive score ≥1) will receive GEN1042 + PEM ± cisplatin or carboplatin + 5-fluorouracil. Secondary endpoints are duration of response, disease control rate, progression-free survival, overall survival, safety/tolerability, and pharmacokinetics. Combination therapy expansion cohorts are recruiting across several countries including Spain, US, and Denmark."

Clinical • Combination therapy • P2b data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD40

A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GEN1042-mIgG2a, an Fc-inert mouse-human chimeric variant of GEN1042 (DuoBody®-CD40x4–1BB), exhibits in vivo antitumor activity and peripheral immune modulation (SITC 2023) - P1/2 | "Establishment of this model has enabled ongoing preclinical exploration of the hypothesis that combining GEN1042 with PD-1 blockade and a platinum-based chemotherapy doublet will potentiate antitumor activity through complementary immune modulatory effects. These data support ongoing clinical studies evaluating the combination of GEN1042 with pembrolizumab and chemotherapy in patients with advanced solid tumors (NCT04083599, NCT05491317)."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD40 • CD86

A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Genmab

Combination therapy • Monotherapy • New P1 trial • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Strength in Partnerships: Duobody CD40x41BB (GEN1042) Therapeutic for Advanced Solid Tumor Treatment (PEGS 2023) - P1/2 | "Preclinical data shows enhanced priming and anti-tumor activity inclusive of T cell proliferation and effector functions. Furthermore, monotherapy and combination data from our FIH, open-label, phase I/II trial (NCT04083599) reveal a manageable safety profile, clinical activity, and pharmacodynamics consistent with the mechanism of action."

Licensing / partnership • Metastases • Oncology • Solid Tumor • CD40

GEN1042 (DuoBody-CD40x4-1BB)®in combination with PD-1 blockade reverses T-cell exhaustion in vitro (AACR 2023) - P1/2 | "These data suggest that, in addition to enhancing T-cell effector functions during T cell priming, GEN1042 can amplify the magnitude of the immune response in combination with PD-1 blockade by re-establishing the functional activity of dysfunctional T cells. GEN1042 is currently being evaluated in patients with advanced solid tumors in a phase 1/2 clinical trial (NCT04083599)."

Combination therapy • IO biomarker • Preclinical • Oncology • Solid Tumor • CD40 • HAVCR2 • IFNG • IL2 • LAG3 • TNFA

Safety and Preliminary Efficacy of GEN1042 (DuoBody®-CD40x4-1BB) Combination Therapy in Advanced Solid Tumors (JSMO 2023) - No abstract available

Clinical • Combination therapy • Metastases • Oncology • Solid Tumor

First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4-1BB (GEN1042) in patients with advanced solid tumors (SITC 2021) - P1/2 | "Conclusions DuoBody-CD40×4-1BB demonstrated biologic and early antitumor activity with a favorable safety profile in patients with advanced solid tumors. Expansion cohorts, including combination therapy with PD-1 inhibitors, are currently enrolling."

Clinical • IO biomarker • P1/2 data • CNS Tumor • Lung Cancer • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • CD8

First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4-1BB (GEN1042) in patients with advanced solid tumors (SITC 2021) - P1/2 | "Expansion cohorts, including combination therapy with PD-1 inhibitors, are currently enrolling. Trial Registration NCT04083599"

Clinical • IO biomarker • P1/2 data • CNS Tumor • Lung Cancer • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • CD8

[VIRTUAL] DuoBody-CD40×4-1BB (GEN1042) induces dendritic-cell maturation and enhances T-cell activation and effector functions in vitro by conditional CD40 and 4-1BB agonist activity (AACR 2021) - P1/2 | "Thereby, DuoBody-CD40×4-1BB provides a unique combination of priming and enhancing existing anti-tumor immunity. DuoBody-CD40×4-1BB is currently being evaluated in patients with advanced solid tumors in a first-in-human trial (NCT04083599)."

IO biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • CD8 • CD86 • CLDN6 • CXCL10 • GZMB • IFNG • LAMP1 • TNFA

Safety and Preliminary Efficacy of GEN1042 (DuoBody®-CD40x4-1BB) Combination Therapy in Patients With Advanced Solid Tumors (ESMO-IO 2022) - P1/2 | "We present data from the safety run-in (SRI) and expansion cohorts investigating GEN1042 + pembrolizumab (PEM) ± standard of care (SoC) CTx. Methods Tx-naive pts with advanced, metastatic/unresectable/recurrent non-CNS tumors received GEN1042 + PEM ± CTx (nab-paclitaxel + gemcitabine or cis/carboplatin + 5-FU) until disease progression or unacceptable toxicity...Encouraging preliminary activity was observed in all patients with HNSCC treated with GEN1042 + PEM + CTx; updated results will be presented. Conclusions GEN1042 + PEM ± SoC CTx was overall well tolerated and showed initial antitumor activity in pts with advanced/metastatic disease."

Clinical • Combination therapy • IO biomarker • Brain Cancer • CNS Tumor • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD40 • PD-L1

A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=75 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=647 | Recruiting | Sponsor: Genmab | N=447 ➔ 647 | Trial primary completion date: Sep 2023 ➔ Oct 2025

Enrollment change • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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

A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=75 | Not yet recruiting | Sponsor: Genmab

New P1/2 trial • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. (PubMed, J Immunother Cancer) - P1/2 | "DuoBody-CD40×4-1BB is capable of enhancing antitumor immunity by modulating DC and T-cell functions and shows biological activity in patients with advanced solid tumors. These findings demonstrate that targeting of these two pathways with an Fc-inert bispecific antibody may be an efficacious approach to (re)activate tumor-specific immunity and support the clinical investigation of DuoBody-CD40×4-1BB for the treatment of cancer."

Journal • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD40