P1, N=250, Recruiting, Mythic Therapeutics | N=150 --> 250

P1/2, N=27, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P2, N=180, Not yet recruiting, AbbVie

P3, N=460, Not yet recruiting, AbbVie

No abstract available

P2, N=100, Not yet recruiting, AbbVie

P3; Trial primary completion date: Jun 2025 --> Mar 2028

P1, N=136, Not yet recruiting, Doma Biopharmaceutical（Suzhou）Co., Ltd.

P3, N=0, Withdrawn, AbbVie | N=250 --> 0 | Not yet recruiting --> Withdrawn

P1, N=237, Active, not recruiting, AbbVie | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Apr 2024 --> Nov 2024

P1/2, N=27, Not yet recruiting, AbbVie

These results highlight the potential of MYTX-011 for treating a broader range of patients with NSCLC with c-MET expression than other c-MET-targeting ADCs. A first-in-human study is ongoing to determine the safety, tolerability, and preliminary efficacy of MYTX-011 in patients with NSCLC (NCT05652868).

P1, N=31, Active, not recruiting, Byondis B.V. | Recruiting --> Active, not recruiting | N=120 --> 31 | Trial completion date: Mar 2025 --> Jul 2024 | Trial primary completion date: Jan 2025 --> Jul 2024

Teliso-V was associated with durable responses in c-Met protein-overexpressing non-squamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

P1, N=155, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=155, Not yet recruiting, MediLink Therapeutics (Suzhou) Co., Ltd.

P2, N=9, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=70 --> 9 | Trial completion date: Oct 2027 --> Mar 2026 | Trial primary completion date: Oct 2026 --> Mar 2025

Of great note, there are currently nine c-Met-targeting ADCs being examined in different phases of clinical studies as well as eight preclinical studies for treating various solid tumors. The purpose of this study is to present a broad overview of clinical- and preclinical-stage c-Met-targeting ADCs.

P1, N=162, Recruiting, AstraZeneca | N=108 --> 162

P3; Trial completion date: Jul 2026 --> Mar 2028

P3; Trial completion date: Mar 2028 --> Jul 2026

P1, N=108, Recruiting, AstraZeneca | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> Oct 2025

P1/2, N=237, Recruiting, Regeneron Pharmaceuticals | N=83 --> 237 | Trial completion date: Dec 2026 --> Feb 2030 | Trial primary completion date: Dec 2026 --> Feb 2030

The resulting biparatopic anti-c-MET ADCs were comparably active on c-MET expressing tumor cell lines as REGN5093 exatecan DAR6 ADC. Structural molecular modeling of paratope combinations for preferential inter-target binding combined with protein engineering for manufacturability yielded deep insights into the capabilities of rational and library approaches. The methodologies of in silico hydrophobicity identification and sequence optimization could serve as a blueprint for rapid development of optimal biparatopic ADCs targeting further tumor-associated antigens in the future.

P1, N=150, Recruiting, Mythic Therapeutics

P1/2, N=106, Recruiting, RemeGen Co., Ltd. | Not yet recruiting --> Recruiting

No abstract available

P2, N=206, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P1, N=220, Recruiting, AbbVie | Not yet recruiting --> Recruiting

Introduction: Telisotuzumab vedotin (Teliso-V) is a first-in-class antibodydrug conjugate that delivers a cytotoxic payload directly to tumor cells with MET protein (or c-Met) OE... MET OE was detected in 25% of samples, most of which were negative for METamp and MET mutations. A subpopulation of METamp patients did not have MET OE. NSCLC with MET OE was associated with worse prognosis compared with NSCLC with no MET OE in the context of standard-of-care treatment.

P2, N=206, Not yet recruiting, AbbVie

P3, N=250, Not yet recruiting, AbbVie

P1, N=220, Not yet recruiting, AbbVie

Enrollment of ≥698 pts is planned across ∼300 sites in ∼40 countries. As of 4 July 2023, 162 sites are actively recruiting in 26 countries including Asia-Pacific countries (China [25 sites], Japan [38 sites], South Korea [5 sites], Taiwan [8 sites], Australia [2 sites]).

Conclusions T + O showed tolerable safety and encouraging efficacy in pts with EGFR-mut, c-Met OE NSCLC with progression on O, regardless of MET amplification status or number of prior L, with an ORR of 53/50% and DCR of 71/76% as per investigators/ICR. T + O may be a potential option for these pts and warrants further clinical investigation.

P1, N=15, Suspended, Open Innovation Partners, Inc. | N=40 --> 15 | Trial completion date: Mar 2023 --> Dec 2023 | Active, not recruiting --> Suspended | Trial primary completion date: Mar 2023 --> Jul 2023

P1, N=460, Recruiting, AbbVie | N=300 --> 460

Secondary endpoints include ORR, duration of response, and patient-reported outcomes. Safety, adverse events (AEs), drug discontinuation or dosing modification due to AEs, and tolerability will be assessed.

Telisotuzumab vedotin (ABBV-399), a first-in-class MET (or c-Met)-directed ADC, had promising monotherapy anticancer activity in previously treated pts with MET-overexpressing (OE), non-squamous EGFR wild type NSCLC (Camidge et al...Conclusions Pts with MET OE NSCLC had worse prognosis compared with those without MET OE, when treated with standard of care including ICI. Given the development of MET-directed ADCs, MET OE (distinct from METamp) may be a future target for characterization and treatment of NSCLC.

Impact of Teliso-V monotherapy on PROs will also be assessed at LUMINOSITY trial conclusion and in the phase 3, TeliMET NSCLC-01 trial (NCT04928846). Table: 1413P Time to deterioration in symptoms, functional domains, and QOL

Background Anti–c-Met (MET protein) antibody-drug conjugate ABBV-400 comprises monoclonal antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor via a stable, cleavable linker. Conclusions ABBV-400 monotherapy showed promising tolerability and efficacy in pts with various MET amp advanced solid tumors. Based on these results, MET amp cohort will be expanded to 60 more pts.