telisotuzumab vedotin (ABBV-399)

In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 (datopotamab deruxtecan and sacituzumab govitecan [SG]) and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing...The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.

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

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

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

No abstract available

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.

P3, N=250, 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.

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

Telisotuzumab vedotin (Teliso-V) is a c-Met ADC, which composed of a c-Met antibody (ABT-700) and a microtubule inhibitor MMAE... In summary, HRA00129-C004 is a novel c-Met targeted ADC with a highly permeable payload demonstrating great stability and anti-tumor activity in both in vitro and in vivo. The promising preclinical data support advancing HRA00129-C004 into clinical testing, and Investigational New Drug (IND) application to NMPA has been submitted.

Telisotuzumab vedotin (Teliso-V) is a c-Met ADC, which composed of a c-Met antibody (ABT-700) and a microtubule inhibitor MMAE... In summary, HRA00129-C004 is a novel c-Met targeted ADC with a highly permeable payload demonstrating great stability and anti-tumor activity in both in vitro and in vivo. The promising preclinical data support advancing HRA00129-C004 into clinical testing, and Investigational New Drug (IND) application to NMPA has been submitted.

P2, N=270, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

P1, N=237, Active, not recruiting, AbbVie | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

P1, N=237, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

The study was open to enrollment as of Nov 2022. Clinical trial information: NCT05513703.

MET amp occurred more frequently in responders; however, Teliso-V activity was not restricted to these pts, as most responders were not MET amplified. Specific genomic alterations beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or did not respond to Teliso-V.

P2, N=70, Recruiting, AbbVie | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Nov 2025 --> Oct 2026

No abstract available

Teliso-V demonstrated a promising ORR in previously treated pts with MET Amp NSQ NSCLC with c-Met OE and improved PFS when compared to last prior systemic cancer therapy. These preliminary data support the ongoing Phase 2 trial of Teliso-V monotherapy in pts with previously untreated MET Amp NSCLC (TeliMET NSCLC-02; NCT05513703), which is currently enrolling.

P2, N=70, Recruiting, AbbVie | Not yet recruiting --> Recruiting

Telisotuzumab vedotin plus erlotinib was safe and effective in EGFR-mutant, c-MET+ non-small cell lung cancer (NSCLC).

Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with EGFR-M+, c-Met+ NSCLC.

Overall T+O efficacy (ORR, DCR, DoR) is shown in the table. Table: 387P Conclusions T + O combination demonstrated tolerable safety and encouraging efficacy with an overall ORR of 50% and DCR of 75% in pts with EGFR-mut, c-Met OE NSCLC who progressed on prior O. This combination may be a potential 2L and 3L Tx option likely to benefit this specific population and deserves further clinical exploration.

P2, N=270, Recruiting, AbbVie | Trial primary completion date: Jan 2025 --> Sep 2025

P2, N=70, Not yet recruiting, AbbVie

P2, N=310, Recruiting, AbbVie | Trial completion date: Jan 2025 --> Sep 2025

P1, N=260, Recruiting, AbbVie | Trial completion date: Dec 2024 --> Dec 2023 | Trial primary completion date: Dec 2024 --> Dec 2023

In a phase 1/1b study (NCT02099058) in patients (pts) with c-Met OE NSCLC, Teliso-V alone or in combination with erlotinib demonstrated an acceptable safety profile and antitumor activity. Teliso-V + Osi is well tolerated with an ORR of 58% (67% at 1.9 mg/kg) in pts with c-Met OE NSCLC who progressed on prior Osi.

Teliso-V demonstrated a promising ORR in pts with previously treated c-Met OE NSQ EGFR WT NSCLC; this cohort is currently expanding in Stage 2. ORR was modest in the cohorts of pts with c-Met OE NSQ EGFR mutant NSCLC and with c-Met OE SQ NSCLC; both cohorts have now met the protocol-specified stopping criteria and are no longer enrolling. The safety profile observed was consistent with IA3.

P3, N=698, Recruiting, AbbVie | Trial completion date: Mar 2027 --> Mar 2028

P3, N=698, Recruiting, AbbVie | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2027 --> Jun 2025

P3, N=698, Ongoing, AbbVie Deutschland GmbH & Co. KG

P1, N=225, Recruiting, AbbVie | Trial primary completion date: Jun 2022 --> Dec 2024