Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 981 |
| INN | Petosemtamab |
| Status | Clinical |
| Drug code(s) | MCLA-158 |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Bispecific |
| Format, general category | Full length Ab |
| Format details | Biclonic |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | EGFR, LGR5 |
| Indications of clinical studies | Head and neck cancer, Colorectal cancer |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | December 15, 2017 |
| Start of Phase 2 | |
| Start of Phase 3 | July 15, 2024 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Merus B.V. |
| Licensee/Partner | None |
| Comments about company or candidate | Sep 2024: First patient has been dosed in the phase 3 trial LiGeR-HN1 evaluating the efficacy and safety of petosemtamab plus pembrolizumab compared to pembrolizumab in 1L PD-L1+ r/m HNSCC July 24, 2024 press release: First patient has been dosed in the company’s Phase 3 trial evaluating the efficacy and safety of petosemtamab compared to investigator’s choice of single agent chemotherapy or cetuximab in previously treated (2/3L) patients with recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) referred to as the LiGeR-HN2 trial (NCT06496178) NCT06496178 Phase 3 in head and neck cancer due to start in July 2024. May 13, 2024 -- Merus N.V. announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for petosemtamab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed following treatment with platinum based chemotherapy and an anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand 1 (PD-L1) antibody. Plan to initiate a phase 3 trial in previously treated HNSCC mid-2024 Phase 1/2 study for Advanced solid tumors NCT03526835 is recruiting as of February 28, 2023. Aug 2023: Described as Phase 1/2; Petosemtamab granted Fast Track Designation for the treatment of patients with recurrent or metastatic head & neck squamous cell carcinoma; Phase 3 trial of petosemtamab monotherapy in previously treated (2L/3L) head and neck squamous cell carcinoma planned to initiate in mid-2024 (https://www.globenewswire.com/news-release/2023/08/07/2720163/37568/en/Merus-Announces-Financial-Results-for-the-Second-Quarter-2023-and-Provides-Business-Update.html) June 2022: Listed as Phase 1 in Merus pipeline accessed online. June 2021: Listed as Phase 1 in Merus pipeline accessed online. Phase 1 results published (https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.3_suppl.62) Conclusions: Dual EGFR/LRG5 blockade with MCLA-158 was well tolerated, and the RP2D was 1500 mg IV q2w. Enrollment of pts with gastric and other non-CRC cancers at the RP2D continues in the expansion phase. Aug 2019: The dose escalation of the Phase 1 clinical trial of MCLA-158 in patients with solid tumors is ongoing. Emerging data for the Phase 1 trial, which will include safety and information around the recommended Phase 2 dose, is expected at the end of 2019. Merus plans to provide further guidance on the program in 2020. NCT03526835 Phase 1 study started May 2, 2018 still recruiting as of Aug 2019. Jan 4 2018: Merus announced approval of a CTA in Belgium, one of the several European countries where Merus has filed a CTA and where it plans to first initiate a Phase 1, first-in-human clinical trial of MCLA-158. MCLA-158 is an ADCC-enhanced Biclonics® designed to bind to cancer stem cells expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). The trial, which will focus initially in patients with metastatic colorectal cancer, is anticipated to start during the first quarter of 2018. Merus plans to file an IND for MCLA-158 with the U.S. FDA in the first quarter of 2018. Merus B.V. is developing MCLA-158 for the treatment of solid tumors, colorectal cancer. |
| Full address of company | CT Utrecht, The Netherlands Europe Netherlands https://merus.nl/about/contact/ |
MCLA-158 is an ADCC-enhanced Biclonics® designed to bind to cancer stem cells expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). This ADCC-enhanced common light chain IgG1 bispecific antibody binds in domain III of EGFR and in the N-Cap/1 st LRR of LGR5, both ligand binding regions, however, only EGF binding was blocked by MCLA-158.
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |