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Abstract CT012: Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC)

EGFR is a known driver of cancer growth, and leucine-rich, repeat-containing, G-protein coupled receptor 5 (LGR5) is a transmembrane receptor expressed on cancer stem cells. Petosemtamab is a human, common… Click to show full abstract

EGFR is a known driver of cancer growth, and leucine-rich, repeat-containing, G-protein coupled receptor 5 (LGR5) is a transmembrane receptor expressed on cancer stem cells. Petosemtamab is a human, common light chain, IgG1 bispecific antibody with ADCC-enhanced activity, targeting EGFR and LGR5, which has shown potent antitumor activity in patient (pt)-derived HNSCC xenograft models. In the dose escalation part of an ongoing phase 1/2 study, the RP2D was established at 1500 mg Q2W, 4 week cycle (JCO 2021:39.3 Sup 62). Petosemtamab is being investigated in the expansion part in pts with selected advanced solid tumors. Promising activity was seen in HNSCC pts previously treated with both platinum-based chemotherapy and checkpoint inhibitors (MCT 2021:20 Sup12 P185). We present data of the expanded HNSCC cohort treated at the RP2D. Primary objective (expansion): investigator-assessed ORR per RECIST 1.1. Secondary objectives: ORR, DOR, PFS (per investigator and central review), OS and safety/tolerability. Key eligibility criteria: advanced/metastatic HNSCC, prior standard therapy, ECOG PS 0-1, measurable disease (RECIST 1.1), baseline tumor biopsy. At the data cutoff date (28 Nov 2022), 49 HNSCC pts were treated. Median age was 63 years (range 31-77), ECOG PS 0/1: 13/35 pts, and 78% were male. Most frequent primary tumor locations were oropharynx (35%), oral cavity (31%), and larynx (16%). 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. A median of 4 treatment cycles (range 1-21) was administered, with 17 pts continuing on therapy at the cutoff. Among 42 pts evaluable for efficacy (≥2 cycles and ≥1 postbaseline scan, or early PD), ORR per investigator was 35.7% (15/42), including 1 CR (ongoing after 18 months), 12 PRs, and 2 unconfirmed PRs with treatment ongoing at the cutoff. 15 pts had SD and DCR was 71.4%. Median DOR was 6.0 months (95%CI=3.3-not calculable). Median PFS was 5.0 months (95%CI=3.2-6.8). Of 78 pts treated at the RP2D (escalation and all expansion cohorts), the most frequent AEs regardless of causality (all grades/G3-4) were rash (33%/0%), hypotension (26%/6%), dyspnea (26%/4%), nausea (26%/1%), dermatitis acneiform (24%/1%), blood magnesium decreased (19%/5%), erythema (19%/0%), diarrhea (19%/0%); IRRs (composite term) were reported in 74%/21% of pts, mostly at the first infusion, and all resolved. 5 pts (6%) discontinued treatment due to IRRs on Day 1. 1 esophageal cancer pt died due to unrelated G5 GI bleeding. Retrospective biomarker analyses will be presented. 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. Citation Format: Ezra E. Cohen, Jérôme Fayette, Amaury Daste, Caroline Even, Christophe Le Tourneau, Irene Brana, Esma Saada, Elisa Fontana, Lara Iglesias, Shumei Kato, Rocio Garcia-Carbonero, Josep Tabernero, Guillem Argilés, Marina Magin, Yu-Ming Shen, Renée de Leeuw, Mohamed Bekradda, Eduardo Pennella, Ernesto Wasserman, Viktoriya Stalbovskaya, Jeroen Lammerts van Bueren, Lokesh Jain, Andrew Joe, Antoine Hollebecque. Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT012.

Keywords: lgr5; igg1 bispecific; petosemtamab; activity; hnscc; cancer

Journal Title: Cancer Research
Year Published: 2023

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