telisotuzumab vedotin (ABBV-399) / AbbVie - LARVOL DELTA

Diffuse interstitial lung disease induced by antibody-drug conjugates (PubMed, Rev Mal Respir) - "Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and therapeutic modalities is required in order to quickly detect and treat ADC-induced ILD."

Journal • Review • Interstitial Lung Disease • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Tumor • CEACAM5 • ERBB3 • HER-2 • MET

Elucidating the mechanism of clinical Teliso-v (cMet-MMAE ADC) and osimertinib combination: A CAV1 and EGFR multi-protein complex controls endolysosomal trafficking of Teliso-V (AACR 2025) - "In addition to osimertinib, other EGFR inhibitors including erlotinib, gefitnib, or afatinib also enhanced Teliso-V EL trafficking which is consistent with the effect of EGFR-MT signaling in suppressing c-Met ADC EL trafficking. Chronic and acute treatment with osimertinib displaces EGFR/c-Met/CAV-1 multimeric signaling complexes leading to improved lysosomal processing of c-Met-targeted ADCs and enhanced tumor cytotoxicity. This study provides mechanistic insights into the combination of Teliso-V and osimertnib in 2L+ EGFRMT NSCLC patients in the clinic."

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAV1 • EGFR • MET

The anti-tumor activity of a novel anti-Her2 and anti-c-Met bispecific antibody-drug conjugate (AACR 2025) - "Its cytotoxic potency was comparable to Trastuzumab-MMAE (T-MMAE) in Her2-high expressing cancer cells and to Telisotuzumab vedotin (Teliso-V) in c-Met-high expressing cancer cells. The novel anti-Her2/anti-c-Met bispecific ADC BB-205 demonstrates superior anti-tumor activity in preclinical studies. BB-205 shows promising therapeutic potential as a first-in-class ADC drug candidate."

Genito-urinary Cancer • Kidney Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • MET

Clinical relevance and translatability of NSCLC patient-derived xenograft (PDX) models for evaluating cMET-targeted therapies (AACR 2025) - "Antibody Drug Conjugates (ADCs), such as c-MET targeting telisotuzumab-vedotin, are emerging as a promising therapy for EGFR inhibitor-progressed NSCLC, but understanding ADC efficacy across diverse profiles of advanced tumors remains a challenge...Notably, Champions low-passage models preserved the molecular and histological features of the original patient tumors, including mutations and copy number variations, which were critical for understanding the response to therapy. Our study highlights the translational potential of Champions PDX models, serving as a platform for investigating the efficacy and mechanisms of resistance to targeted therapies."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Telisotuzumab vedotin: Accelerated approval in US for 2L high c-met NSCLC in Q2 2025 (AbbVie) - Q1 2025 Results

FDA approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Association of genomic alterations in circulating tumor DNA (ctDNA) with clinical response to telisotuzumab vedotin (Teliso-V) in 2L+ EGFR wildtype ( EGFRwt) non-squamous non-small cell lung cancer (NSCLC) patients (pts) with c-Met overexpression (OE). (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT03539536 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Circulating tumor DNA • Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

LUMINOSITY, a phase 2 study of telisotuzumab vedotin in patients with c-Met protein–overexpressing non-squamous EGFR-wildtype advanced NSCLC: Efficacy outcomes by prior therapy. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT03539536 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

TeliMET NSCLC-04: A phase 2, open-label, randomized, global study of 2 telisotuzumab vedotin regimens in patients with previously treated c-Met protein–overexpressing, locally advanced/metastatic non-squamous EGFR wildtype non-small cell lung cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06568939 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Recent advances in therapeutic strategies for non-small cell lung cancer. (PubMed, J Hematol Oncol) - "For instance, amivantamab has been approved as a treatment for epidermal growth factor receptor (EGFR)-mutant NSCLC, including those with EGFR exon 20 insertion mutations. Additionally, antibody-drug conjugates (ADCs), including HER2-targeting trastuzumab deruxtecan, TROP2-targeting ADCs, HER3-targeting patritumab deruxtecan, and MET-targeting telisotuzumab vedotin, have demonstrated promising outcomes in several clinical trials. This review summarizes the recent advancements and challenges associated with the evolving NSCLC therapeutic landscape."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

Clinical Value of Testing for c-Met Protein Overexpression in Patients With Non-Small Cell Lung Cancer (ISPOR 2025) - "OBJECTIVES: This study evaluated the clinical value of testing patients with advanced/metastatic EGFR wild-type non-squamous non-small cell lung cancer (NSCLC) with MET immunohistochemistry (IHC) to identify those with high and high/intermediate c-Met protein overexpression (OE), who would then be eligible for telisotuzumab vedotin (Teliso-V), an investigational antibody-drug conjugate. A deterministic decision-tree (for treatment and MET IHC testing allocations) into a stochastic partition-survival model (for efficacy-related outcomes) was used to evaluate clinical utility of MET IHC testing... The model findings suggest clinical value in implementing testing for c-Met protein OE among all eligible NSCLC patients, as demonstrated by improved outcomes among patients when MET IHC testing is conducted."

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Telisotuzumab vedotin: Accelerated approval in US for 2L NSCLC in 2025 (AbbVie) - Q4 2024 Results

Accelerated approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein–overexpressing nonsquamous EGFR wildtype advanced NSCLC: Updated analysis of the LUMINOSITY trial (ELCC 2025) - P2 | "In this updated analysis, Teliso-V monotherapy 1.9 mg/kg in pts with c-Met protein OE EGFR WT NSQ NSCLC continued to demonstrate durable responses, with an enrichment in the c-Met–high population. No new safety signals were observed.Table 18PEfficacy endpointsDOR, duration of response; OS, overall survival; PFS, progression-free survival.aPer independent central review."

Clinical • Metastases • Monotherapy • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Treatment of c-MET Antibody-Drug Conjugate Asymptomatic Pneumonitis with a Novel Steroid Regimen in Non-Small Cell Lung Cancer: A Case Report. (PubMed, J Immunother Precis Oncol) - "We report a case of a patient with metastatic non-small cell lung cancer taking the ADC telisotuzumab vedotin (Teliso V) plus osimtertinib who developed ADC-induced pneumonitis despite clinical benefit. This patient was able to tolerate treatment for a prolonged period on a novel steroid regimen, using steroids when pneumonitis was asymptomatic but radiologically evident and as a daily suppressant. This treatment strategy may have implications in the broader management of ADC-interstitial lung disease/pneumonitis and underscores its potential mechanisms."

Journal • Inflammation • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • MET

ABBV – 400: A c-Met Targeting ADC With Activity in CRC & MET Amplified Tumours (ADC London 2025) - "• Exploring the elusive targeting of c-Met protein • Reviewing the limitations of small molecule inhibitors and antibodies • Discussing next generation ADCs that are effective at targeting the c-Met protein: Teliso-V, Temab-A"

Oncology • MET

M14-237: A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=237 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Teliso-V and osimertinib: the METamorphosis of EGFR-mutant lung cancer? (PubMed, Ann Oncol) - No abstract available

Journal • Lung Cancer • Oncology • Solid Tumor • EGFR

Antibodies to watch in 2025. (PubMed, MAbs) - "In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key..."

Journal • Review • Oncology

A Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Vedotin (ABBV-399) Moves Through the Body as a Monotherapy in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Monotherapy • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib. (PubMed, Ann Oncol) - P1 | "Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population."

Journal • P1 data • Cardiovascular • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • EGFR • MET

METRIX: International real-world study of c-Met protein overexpression in patients with non-small cell lung cancer (ESMO Asia 2024) - "Background The c-Met (MET protein)-directed antibody-drug conjugate telisotuzumab vedotin had promising efficacy in patients (pts) with EGFR wildtype nonsquamous non-small cell lung cancer (NSQ NSCLC) and c-Met protein overexpression (OE)...Understanding the prevalence of c-Met protein OE in different pt populations and its overlap with other biomarker alterations could aid in therapy decisions. Future results from METRIX will expand these data."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK1 • BRAF • EGFR • KRAS • MET • PD-L1 • ROS1

Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions. (PubMed, Antibodies (Basel)) - " Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody...Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 1b Study of Telisotuzumab Vedotin (Teliso-V) and Osimertinib in Patients (Pts) With Advanced EGFRMutated (Mut), c-Met Overexpressing (OE) Non-Small Cell Lung Cancer (NSCLC): Final Efficacy and Safety Updates (AIOM 2024) - P1 | "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 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."

Clinical • Metastases • P1 data • Anemia • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • MET

A Study to Assess Disease Activity of Intravenously (IV) Infused Telisotuzumab Vedotin in Adult Participants With Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=9 | Terminated | Sponsor: AbbVie | Trial completion date: Mar 2026 ➔ Oct 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ Oct 2024; Strategic considerations

Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC) (AIOM 2024) - P2 | "METamp occurred more frequently in responders; but Teliso-V activity wasn’t restricted to these pts: most responders weren’t METamplified. Specific genomic alts beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or didn’t respond to Teliso-V."

Circulating tumor DNA • Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • MET

Telisotuzumab vedotin: Regulatory approval for non-squamous NSCLC (based on LUMINOSITY trial) in H1 2025 (AbbVie) - Q3 2024 Results

Approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology