petosemtamab (GEN-1158) / Genmab - LARVOL DELTA

A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2) (clinicaltrials.gov) - P3 | N=621 | Active, not recruiting | Sponsor: Merus B.V. | Recruiting ➔ Active, not recruiting

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

Clinical and correlative outcomes of petosemtamab ± pembrolizumab (pembro) in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) (ESMO 2026) - P1/2 | "Updated clinical data will be presented.Conclusions In r/m HNSCC, 1L petosemtamab + pembro demonstrated clinically meaningful, durable activity with no new safety signals. Correlative analyses showed enhanced intratumoral immune cell infiltration and activation of immune-related gene expression in responding tumors, indicating a mechanistic link between petosemtamab's immune-engaging biology and clinical benefit, and supporting continued clinical development."

Clinical • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2) (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Merus N.V. | Not yet recruiting ➔ Recruiting

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

MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=560 | Recruiting | Sponsor: Merus B.V. | Trial primary completion date: Nov 2025 ➔ May 2028 | Trial completion date: Nov 2027 ➔ Nov 2028

First-in-human • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=567 | Recruiting | Sponsor: Merus N.V. | N=360 ➔ 567 | Trial completion date: Jun 2025 ➔ Nov 2027 | Trial primary completion date: Jun 2024 ➔ Nov 2025

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=360 | Recruiting | Sponsor: Merus N.V. | Unknown status ➔ Recruiting | Phase classification: P1 ➔ P1/2 | N=120 ➔ 360 | Trial completion date: Jan 2021 ➔ Jun 2024 | Trial primary completion date: Jan 2021 ➔ Jun 2023

Enrollment change • Enrollment open • First-in-human • Phase classification • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Merus N.V.

First-in-human • New P1 trial • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2) (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: Merus N.V.

Monotherapy • New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=360 | Recruiting | Sponsor: Merus N.V. | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2023 ➔ Jun 2024

First-in-human • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Petosemtamab plus chemotherapy in metastatic colorectal cancer (mCRC): Updated results from a phase 2 trial (ESMO 2026) - P1/2 | "2L pts could have received 1 prior chemotherapy regimen ± bevacizumab (bev)...Table: 822P Key outcomes (left + right sides) Efficacy, n (%) Petosemtamab + FOLFOX/FOLFIRI 1L (n=17) 2L (n=20) ORRa 14 (82) 14 (70) CR 1 (6) 0 PRa 13 (76) 14 (70) DCR 17 (100) 18 (90b) TEAEs (≥25% of pts) 1L/2L petosemtamab + FOLFOX (n=27) 1L/2L petosemtamab + FOLFIRI (n=26) Any G G3/4 Any G G3/4 Dermatitis acneiform 13 (48) 0 12 (46) 1 (4) Diarrhea 9 (33) 0 12 (46) 3 (12) Stomatitis 9 (33) 0 9 (35) 1 (4) Fatigue 8 (30) 2 (7) 9 (35) 1 (4) Blood magnesium decreased 8 (30) 0 4 (15) 0 Dry skin 7 (26) 0 6 (23) 0 Neuropathy peripheral 7 (26) 0 0 0 Peripheral sensory neuropathy 7 (26) 1 (4) 1 (4) 0 Nausea 6 (22) 0 9 (35) 0 Abdominal pain 5 (19) 1 (4) 7 (27) 3 (12) Vomiting 5 (19) 1 (4) 7 (27) 1 (4) aConfirmed + unconfirmed. bTwo patients not evaluable. Conclusions With more patients treated and longer follow-up, petosemtamab + chemotherapy continue to show promising antitumor activity..."

Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metastatic Colorectal Cancer (LiGeR-CRC2) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metastatic Colorectal Cancer (LiGeR-CRC2) (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Genmab

New P3 trial • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Upcoming treatments (EADV 2026) - "Cytokines are small, low-molecular-weight proteins (~5–25 kDa) that serve as critical chemical messengers for cell-to-cell communication within the immune system. Produced by a wide range of cells, including immune cells (such as T cells, B cells, macrophages, and natural killer cells) and non-immune cells (such as endothelial, fibroblast, and epithelial cells), they regulate immunity, inflammation, and hematopoiesis.Key Approved Monoclonal AntibodiesPembrolizumab (Keytruda): Blockade of the PD-1 immune checkpoint for multiple solid tumors including melanoma and non-small cell lung cancer.Trastuzumab (Herceptin): Targeting of the HER2 receptor in HER2-positive breast cancers.Lecanemab (Leqembi): Clearance of brain amyloid-beta plaques for early-stage Alzheimer's disease.Blinatumomab (Blincyto): Bispecific T-cell engager utilized for B-cell precursor acute lymphoblastic leukemia.Emerging Formats and Pipeline DrugsBispecific and Multispecific Antibodies: Engineered to..."

Acute Lymphocytic Leukemia • Alzheimer's Disease • Breast Cancer • Chronic Spontaneous Urticaria • CNS Disorders • Dermatology • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Leukemia • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Pruritus • Solid Tumor • Urticaria • HAVCR2 • HER-2 • LAG3 • TIGIT

Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer (LiGeR-CRC1) (clinicaltrials.gov) - P3 | N=960 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS

Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer (LiGeR-CRC1) (clinicaltrials.gov) - P3 | N=960 | Not yet recruiting | Sponsor: Genmab

New P3 trial • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS

Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC) (AACR 2023) - "Pts received a median of 2 (range 1-4) lines of prior systemic therapy, including anti-PD-1/PD-L1 in 96% of pts and platinum-based chemotherapy in 92% of pts; 2 pts received prior cetuximab. Petosemtamab demonstrates promising clinical efficacy with a manageable safety profile in pretreated HNSCC pts. Further clinical development in HNSCC is planned with petosemtamab monotherapy and in combination with SOC."

Clinical • IO biomarker • Metastases • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

LiGeR-HN1: A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1) (clinicaltrials.gov) - P3 | N=699 | Active, not recruiting | Sponsor: Merus B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • PD-L1

Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 study. (ASCO 2024) - P1/2 | "Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab demonstrates a well-tolerated safety profile and promising preliminary clinical efficacy as 1L treatment for pts with r/m HNSCC."

Clinical • Metastases • P2 data • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGR5

Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 trial. (ASCO 2025) - P1/2, P3 | "Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab continues to demonstrate promising clinical efficacy and a well-tolerated safety profile as 1L treatment for pts with r/m PD-L1+ HNSCC. A global phase 3 trial, LiGeR-HN1 (NCT06525220), is ongoing to evaluate petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC."

Clinical • Metastases • P2 data • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

MCLA-158-CL04: Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Merus B.V. | Initiation date: Mar 2025 ➔ Mar 2026

Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Petosemtamab: Data from P3 LiGeR-HN1 trial (NCT06525220) for 1L PD-L1+ R/M HNSCC in Q4 2026 (Genmab A/S) - Q2 2026 Results: Data from P3 LiGeR-HN2 trial (NCT06496178) for 2/3L HNSCC in Q1 2027

P3 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

MCLA-158-CL04: Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Merus B.V. | N=180 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

HPV Status Shapes the Therapeutic Rationale for Bispecific Antibodies in R/M HNSCC (EACR 2026) - "Amivantamab, Petosemtamab, Ivonescimab, and Ficerafusp alfa are emerging targeted bispecific/bifunctional antibodies under investigation... This study provides biological validation of bispecific and bifunctional antibody use in R/M HNSCC setting. In particular, we identified that the therapeutic benefit is correlated to HPV status. In the future, survival analysis will be integrated in order to validate this data."

Bispecific • IO biomarker • Head and Neck Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • TGFB1 • TGFBR2

Petosemtamab plus pembrolizumab as first-line (1L) treatment of PD-L1 high metastatic non-small cell lung cancer (NSCLC): Global phase 2 trial. (ASCO 2026) - P2 | "The primary objective is investigator-assessed objective response rate. Enrollment of approximately 80 patients in North America, EU, and Asia-Pacific is planned."

Clinical • IO biomarker • Metastases • P2 data • Tumor mutational burden • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGR5 • PD-L1 • TMB

Recent highlights and breakthroughs in immunotherapy for head and neck cancers. (PubMed, Curr Opin Oncol) - "Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors."

IO biomarker • Journal • Head and Neck Cancer • Nasopharyngeal Carcinoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF