petosemtamab (MCLA-158) / Merus - LARVOL DELTA

LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC. (PubMed, Future Oncol) - P3 | "LiGeR-HN2 (NCT06496178) evaluates petosemtamab versus investigator's choice of monotherapy (cetuximab, methotrexate, or docetaxel) in patients with previously treated r/m HNSCC. Primary endpoints in both trials are objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review, and overall survival. Both trials are recruiting at the time of publication.Clinical Trial Registration: NCT06525220 and NCT06496178 (ClinicalTrials.gov)."

Journal • Monotherapy • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • 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

Petosemtamab, a Bispecific Antibody Targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G Repeat-Containing Protein-Coupled Receptor (LGR5) Designed for Broad Clinical Applications. (PubMed, Cancers (Basel)) - "The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC."

Journal • Review • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Merus’ Petosemtamab with Pembrolizumab Interim Data Demonstrates Robust Efficacy and Durability in 1L PD-L1+ r/m HNSCC (Merus Press Release) - P1/2 | N=53 | NCT03526835 | Sponsor: Merus N.V. | "Observations in the presentation include as of a February 27, 2025 data cutoff date: 45 patients (pts) were treated The efficacy evaluable population consisted of 43 patients who were treated (with one or more doses) as of the data cutoff date and either ≥1 post-baseline tumor assessment, or discontinued early due to disease progression or death Median follow up of 14.3 months for the 45 patients In 43 evaluable patients: Confirmed overall response rate: 63% (27/43, 95% CI: 49-75), including 6 complete responses, 21 partial responses by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment, including: 4 of 8 patients with HPV associated cancer responded Responses observed across PD-L1 levels (CPS 1-19: 47% [8/17]; CPS > 20: 73% [19/26]) Median progression-free survival was 9 months (95% CI: 5.2-12.9)..."

P2 data • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the First Quarter 2025 and Provides Business Update (GlobeNewswire) - "A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25."

Enrollment status • P2 data • Colorectal Cancer

Merus Announces the Journal Publication of Petosemtamab Mechanism of Action (GlobeNewswire) - "Merus N.V...announced publication on the mechanism of action of petosemtamab, a bispecific antibody targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G (LGR5), in the scientific journal 'Cancers', a MDPI publication....'This publication outlining the scientific rationale for petosemtamab, a bispecific targeting EGFR and LGR5, underpins the strong previously reported phase 2 interim clinical data in both 1L PD-L1+ r/m HNSCC in combination with pembrolizumab and as a single-agent in 2L+ r/m HNSCC.'"

Clinical • Trial status • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Merus Announces Abstract Accepted for Presentation at the 2025 ASCO Annual Meeting (GlobeNewswire) - "Merus N.V...today announced the acceptance of an abstract for presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, Illinois on May 30- June 3, 2025. An updated analysis of the interim clinical data from the phase 2 trial of petosemtamab with pembrolizumab as 1L treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) will be presented in a poster at 2025 ASCO. The presentation will include data on the entire 45 patient dataset and follows the early clinical efficacy and encouraging safety data previously presented at 2024 ASCO."

P2 data • Squamous Cell Carcinoma of Head and Neck

Topical strategy to prevent skin toxicities from bispecific-EGFR inhibitors by blocking drug-receptor interactions in skin (ESMO-TAT 2025) - "In our previous work, we developed a compound and method to prevent "on-target" skin toxicity by topically blocking the drug-receptor interactions of cetuximab and panitumumab at the site of toxicity...To gain deeper insights into the mechanism of action, in silico docking experiments were conducted to understand how SDT-011 blocks amivantamab, petosemtamab, and izalontamab. SDT-011 demonstrated effective blocking of anti-EGFR bispecific monoclonal antibodies binding to EGFR, including amivantamab, petosemtamab, and izalontamab... SDT-011 offers a promising approach for treating on-target skin toxicity by topically blocking EGFRi monoclonal and bispecific antibodies at the site of toxicity. By potentially reducing the incidence and severity of skin toxicities associated with EGFR inhibitors, SDT-011 could improve patients' quality of life and treatment compliance, ultimately enhancing the overall effectiveness of cancer therapies."

Oncology

Merus Announces Financial Results for the Fourth Quarter and Full Year 2024 and Provides Business Update (GlobeNewswire) - "Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors - (i) LiGeR-HN1 phase 3 trial in 1L PD-L1+ r/m head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L r/m HNSCC enrolling - we expect both trials to be substantially enrolled by YE25; (ii) clinical update on phase 2 trial in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC planned for 1H25; (iii) phase 2 trial in 1L, 2L and 3L+ metastatic colorectal cancer (mCRC) enrolling; mCRC initial clinical data planned for 2H25."

Enrollment status • P2 data • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Petosemtamab granted Breakthrough Therapy designation by the U.S. FDA for 1L PD-L1 positive head and neck squamous cell carcinoma (GlobeNewswire) - "Merus...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (r/m HNSCC) with combined positive score (CPS) ≥ 1....BTD is supported by updated data from the ongoing phase 1/2 open-label, multicenter trial evaluating petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) (NCT03526835)."

Breakthrough therapy • Evidence highlight • Squamous Cell Carcinoma of Head and Neck • PD-L1

Merus announces First Patient Dosed in Phase 2 Trial of Petosemtamab in 3L+ mCRC (GlobeNewswire) - "Merus...announced that the first patient has been dosed in the Company’s phase 2 trial evaluating petosemtamab monotherapy in heavily pretreated (3L+) metastatic colorectal cancer (mCRC)....The phase 2, open-label trial will evaluate the safety and antitumor activity of petosemtamab monotherapy in 3L+ mCRC, post anti-EGFR therapy. To be eligible for enrollment, patients must lack certain mutations as detected in plasma by ctDNA NGS, including KRAS, NRAS."

Trial status • Colorectal Cancer

Petosemtamab Clinical Development (GlobeNewswire) - "r/m HNSCC:...phase 2 trial of petosemtamab in combination with pembrolizumab in PD-L1+ 1L HNSCC ongoing with a clinical data update planned for 2025; mCRC:...phase 2 trial in 1L mCRC in combination with standard chemotherapy planned to initiate in 2025, and phase 2 trial in 3L+ monotherapy planned to initiate in 2025; mCRC initial clinical data planned for 2025."

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

Merus’ Petosemtamab Monotherapy Interim Data Continues to Demonstrate Clinically Meaningful Activity in 2L+ r/m HNSCC (GlobeNewswire) - P1/2 | N=567 | NCT03526835 | Sponsor: Merus N.V. | "As of a July 5, 2024 data cutoff date, 82 pts were treated with petosemtamab 1500 mg Q2W...Confirmed overall response rate (ORR): 36% (90% CI: 27–46; 27/75) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment, including 4 complete responses (CRs), with one CR continuing on treatment for more than 3 years as of the data cutoff; and 13% (2/15) ORR in HPV associated cancer with another 5 patients achieving stable disease...Median duration of response (DOR), progression free survival (PFS) and overall survival (OS) were 6.2, 4.9 and 11.4 months...As of a July 5, 2024 data cutoff date, 28 pts were treated with petosemtamab 1100 mg Q2W...ORR: 19% (90% CI: 8–35; 5/27), including 2 CRs, by RECIST v1.1. per investigator assessment."

P1/2 data • Squamous Cell Carcinoma of Head and Neck

Petosemtamab (MCLA-158) monotherapy in previously treated (2L+) recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase II trial (ESMO Asia 2024) - P1/2 | "Petosemtamab was well tolerated at both dose levels; no new safety signals observed. Conclusions Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, continues to demonstrate promising clinical efficacy with a well-tolerated safety profile in 2L+ HNSCC."

Metastases • Monotherapy • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGR5

Merus Announces Publication of an Abstract on Petosemtamab as 2L+ treatment of r/m HNSCC at the ESMO Asia Congress 2024 (GlobeNewswire) - P1/2 | N=567 | NCT03526835 | Sponsor: Merus N.V. | "Observations in the abstract include: 47 pts were evaluable for response (≥4 months follow up prior to data cutoff date and ≥1 post baseline scan, or early progressive disease (PD)) and overall response rate was 40.4% (19/47 and 1 unconfirmed partial response (PR) that confirmed post cutoff, 20/47) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment; 7.2 months median duration of response; 5.1 months median progression free survival; 12.5 months median overall survival; Petosemtamab was well tolerated at both dose levels; no new safety signals observed; No grade 5 treatment emergent adverse events were reported."

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

Petosemtamab plus pembrolizumab vs. pembrolizumab alone for first-line (1L) treatment of recurrent/metastatic (r/m) PD-L1–positive head and neck squamous cell carcinoma (HNSCC): A randomized, open-label, phase III trial (ESMO 2024) - P1/2 | "The primary objectives are to compare overall response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) and overall survival in pts treated with petosemtamab plus pembrolizumab vs. pembrolizumab. Secondary objectives include evaluation of antitumor activity (measured by progression-free survival, duration of response, clinical benefit rate [all per RECIST v1.1 by BICR and by investigator assessment] and ORR per investigator assessment), safety and tolerability, and health-related quality of life (EuroQol EQ-5D-5L, EORTC QLQ-H&N43, Patient Global Impression of Change)."

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Petosemtamab compared with investigator's choice monotherapy in previously treated patients (pts) with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): A randomized, open-label, phase III trial (ESMO 2024) - P1/2 | "Pts will be randomized 1:1 to receive either petosemtamab intravenously (IV) every 2 weeks, or investigator's choice monotherapy (cetuximab IV once, then once weekly [QW]; methotrexate IV push QW; or docetaxel IV QW). The primary objectives are to compare overall response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) and overall survival in pts treated with petosemtamab vs. investigator's choice monotherapy. Secondary objectives include evaluation of antitumor activity (measured by ORR [by investigator assessment], and progression-free survival, duration of response, time to response, clinical benefit rate [all per BICR and investigator; per RECIST v1.1]), the safety and tolerability of petosemtamab, and health-related quality of life (EORTC QLQ-C30, EORTC QLQ-H&N43)."

Clinical • Metastases • Monotherapy • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGR5

Merus Announces First Patient Dosed in LiGeR-HN1, a Phase 3 Trial Evaluating Petosemtamab in Combination with Pembrolizumab in 1L r/m HNSCC (GlobeNewswire) - "Merus N.V...announced that the first patient has been dosed in the Company’s phase 3 trial evaluating the efficacy and safety of petosemtamab, a Biclonics targeting EGFR and LGR5, in combination with pembrolizumab, compared to pembrolizumab as first line (1L) therapy for patients with PD-L1+ recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC), referred to as the LiGeR-HN1 trial....Merus plans to enroll approximately 500 patients in the trial."

Trial status • Squamous Cell Carcinoma of Head and Neck

Merus announces acceptance of abstracts for presentation at ESMO Asia Congress 2024 (GlobeNewswire) - "Merus NV...announced the acceptance of an abstract on petosemtamab, a Biclonics antibody targeting EGFR and LGR5, in previously treated (2L+) patients with recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC), for presentation at the European Society for Medical Oncology (ESMO) Asia 2024 Congress, being held in Singapore from December 6-8, 2024."

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

Merus Announces Abstract Accepted for Presentation at the ESMO Asia Congress 2024 (GlobeNewswire) - "Merus N.V...today announced the acceptance of an abstract on petosemtamab...in previously treated (2L+) patients with recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) for presentation at the European Society for Medical Oncology (ESMO) Asia Congress 2024 taking place in Singapore December 6-8, 2024...The abstract will be available on the ESMO Asia Congress website on Sunday, Dec. 1, 2024 at 11:05 a.m. ET....The presentation at ESMO Asia will include updated efficacy, durability and safety data from that initial 2L+ HNSCC cohort along with interim data from the dose optimization cohort evaluating petosemtamab monotherapy 1500 or 1100 mg dose levels in 2L+ HNSCC."

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

MCLA-158-CL03: A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Merus N.V. | Not yet recruiting ➔ Recruiting

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

Merus Announces Financial Results for the Second Quarter 2024 and Provides Business Update (GlobeNewswire) - "Clinical data update on 2L+ HNSCC planned for late fourth quarter of 2024....Merus has confirmed through feedback with the U.S. Food and Drug Administration (FDA) that petosemtamab 1500 mg every two weeks is appropriate for further development in HNSCC as monotherapy, and in combination with pembrolizumab....Merus plans to initiate LiGeR-HN1, a phase 3 trial evaluating petosemtamab in combination with pembrolizumab in 1L HNSCC by year end 2024."

FDA event • P1/2 data • Trial initiation date • Squamous Cell Carcinoma of Head and Neck

A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Recurrent or Metastatic PD-L1+ Head and Neck Squamous Cell Carcinoma Patients (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: Merus N.V.

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

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

Enrollment open • Metastases • 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=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 • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • 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 • EGFR