telisotuzumab (h224G11) / Pierre Fabre, AbbVie - LARVOL DELTA

Phase 2 randomized study evaluating safety, efficacy, and optimal dose of ABBV-400 in combination with fluorouracil, folinic acid, and bevacizumab in previously treated patients with metastatic colorectal cancer. (ASCO-GI 2025) - P2 | "ABBV-400 is a c-Met–directed antibody-drug conjugate composed of the monoclonal antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload...In stage 2, patients are randomized to up to 4 ABBV-400 dose cohorts (2 with Q2W and 2 with Q4W ABBV-400 schedule; all in combination with Q2W 5-FU, FA, and bev) and a comparator cohort (irinotecan [180 mg/m2] + 5-FU [400 mg/m2 bolus and 2400 mg/m2 infusion] + FA [200 mg/m2] + bev [5 mg/kg]; all Q2W). Patients are treated until progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment was initiated in November 2023, with 3 patients enrolled as of January 4, 2024."

Clinical • Combination therapy • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • MET

First-in-human study of ABBV-400, a novel c-Met–targeting antibodydrug conjugate, in advanced solid tumors: Results in colorectal cancer (AIOM 2024) - P1 | "ADC ABBV-400 comprises c-Met–targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. ABBV-400 at 2.4 and 3.0mg/kg Q3W has tolerable and manageable safety profile with promising antitumor activity. Long-term tolerability appears improved at 2.4 relative to 3.0mg/kg with higher relative dose intensity and generally lower TEAEs. The study is also evaluating ABBV-400 with bevacizumab in CRC pts."

Metastases • P1 data • Anemia • Colorectal Cancer • Fatigue • Interstitial Lung Disease • Leukopenia • Neutropenia • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • MET

Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (AIOM 2024) - P1 | "The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations."

Circulating tumor DNA • Clinical • Metastases • Tumor mutational burden • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • KRAS • LRP1B • MET • MSI • PTPRT • TMB • TOP1 • TP53

Efficacy of ABBV-400 monotherapy in patients with MET gene amplified advanced solid tumors (AIOM 2024) - P1 | "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. 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."

Clinical • Metastases • Monotherapy • Anemia • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Hematological Disorders • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study (ESMO 2024) - P1 | "ABBV-400 is an ADC composed of the c-Met–targeting mAb telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. ABBV-400 has a tolerable safety profile and antitumor activity in pts with NSQ EGFR WT NSCLC, warranting further investigation. Evaluation of ABBV-400 in other NSCLC subtypes is ongoing. Table: 1257MO Preliminary efficacya aTime-to-event endpoints (PFS, DOR, OS) are immature.bConfirmed responses.CBR, clinical benefit rate; CR, complete response; NE, not estimated; NSQ, non-squamous; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease"

Clinical • Metastases • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

ABBV-400, a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced gastric/gastroesophageal junction adenocarcinoma (GEA): Results from a phase I study (ESMO 2024) - P1 | "ABBV-400 is an ADC consisting of the c-Met–targeting mAb telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. ABBV-400 demonstrated a tolerable safety profile and antitumor activity in pts with advanced GEA, warranting additional study in future clinical trials."

Clinical • Metastases • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

Dr Levy on the Clinical Application of ADCs in NSCLC Following ASCO 2024 Data (OncLive) - "Benjamin Levy, MD...discuss the clinical application of antibody-drug conjugates in non-small cell lung cancer."

Video

Phase 2 randomized study evaluating safety, efficacy, and optimal dose of ABBV-400 in combination with fluorouracil, folinic acid, and bevacizumab in previously treated patients with metastatic colorectal cancer. (ASCO 2024) - P2 | "ABBV-400 is a c-Met–directed antibody-drug conjugate composed of the monoclonal antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload...In stage 2, patients are randomized to up to 4 ABBV-400 dose cohorts (2 with Q2W and 2 with Q4W ABBV-400 schedule; all in combination with Q2W 5-FU, FA, and bev) and a comparator cohort (irinotecan [180 mg/m 2 ] + 5-FU [400 mg/m 2 bolus and 2400 mg/m 2 infusion] + FA [200 mg/m 2 ] + bev [5 mg/kg]; all Q2W). Patients are treated until progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment was initiated in November 2023, with 3 patients enrolled as of January 4, 2024."

Clinical • Combination therapy • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • MET

First-in-human study of ABBV-400, a novel c-Met–targeting antibody-drug conjugate, in advanced solid tumors: Results in colorectal cancer. (ASCO 2024) - P1 | "The antibody-drug conjugate ABBV-400 comprises c-Met–targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. ABBV-400 at 2.4 and 3.0 mg/kg Q3W has a tolerable and manageable safety profile, with promising antitumor activity. Long-term tolerability appears improved at 2.4 relative to 3.0 mg/kg, with higher relative dose intensity and generally lower TEAEs. The study is also evaluating ABBV-400 with bevacizumab in pts with CRC."

Metastases • P1 data • Anemia • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Interstitial Lung Disease • Leukopenia • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • MET

Phase 1b study evaluating the efficacy and safety of ABBV-400, a c-Met–targeting antibody-drug conjugate, in select advanced solid tumor indications. (ASCO 2024) - P1 | "ABBV-400 is an antibody-drug conjugate, consisting of the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. Sharma et al. JCO 2023; 41[16 suppl]:3015."

Clinical • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2 • MET

Efficacy of ABBV-400 monotherapy in patients with MET gene amplified advanced solid tumors (ESMO 2023) - P1 | "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."

Clinical • Metastases • Monotherapy • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (ESMO 2023) - P1 | "The antibody-drug conjugate ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. A molecular response was observed in 48% (14/29) of all evaluated pts and 47% (8/17) of pts with CRC; median change from baseline tumor size was -22.5% and -20.3%, respectively. Table: 163P Pts with molecular response and correlation between baseline biomarker status and radiographic response Conclusions ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including in pts with high TMB and KRAS mutations."

Circulating tumor DNA • Clinical • Metastases • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • KRAS • LRP1B • MET • MSI • PTPRT • TMB • TOP1 • TP53

Dose escalation results from a first-in-human study of ABBV-400, a novel c-Met–targeting antibody-drug conjugate, in advanced solid tumors. (ASCO 2023) - P1 | "The antibody-drug conjugate (ADC) ABBV-400 consists of the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor (Top1i) payload. On the basis of DLTs, a maximum tolerated dose of ABBV-400 was identified. At this dose, safety results appear comparable with other Top1i ADCs. Promising antitumor activity was seen with ABBV-400 across tumor types, justifying further evaluation in the ongoing dose expansion in NSCLC, GEA, and CRC."

Metastases • P1 data • Anemia • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Fatigue • Gastric Cancer • Gastrointestinal Cancer • Interstitial Lung Disease • Leukopenia • Lung Cancer • Melanoma • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Uterine Cancer • EGFR • MET

Phase I Study of ABBV-399 (Telisotuzumab Vedotin) as Monotherapy and in Combination with Erlotinib in NSCLC (WCLC 2017) - P1; "ABBV-399 is a first-in-class antibody-drug conjugate composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). ABBV-399 is well tolerated at 2.7 mg/kg once every 21 days and has demonstrated antitumor activity in pts with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Early evidence suggests that ABBV-399 represents a novel treatment paradigm effective against multiple c-Met+ NSCLC molecular subtypes and histologies. Updated efficacy/safety data and c-Met IHC status will be presented."

Combination therapy • Monotherapy • P1 data • Non Small Cell Lung Cancer

Phase I study of ABBV-399, a c-Met antibody-drug conjugate (ADC), as monotherapy and in combination with erlotinib in patients (pts) with non-small cell lung cancer (NSCLC). (ASCO 2017) - P1; "ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). ABBV-399 is well tolerated at 2.7 mg/kg once every 21 days and has demonstrated antitumor activity in pts with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated efficacy/safety data and MET gene status will be presented."

Combination therapy • Monotherapy • P1 data • Biosimilar • Gene Therapies • Non Small Cell Lung Cancer • Pain

[VIRTUAL] Evaluating telisotuzumab vedotin in combination with osimertinib in patients with advanced non-small cell lung cancer: A phase I/Ib study cohort (ESMO 2020) - P1 | "Funding: AbbVie Inc. Clinical trial identification: NCT02099058."

Clinical • Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Second-Line, Biomarker-Driven Therapies for Squamous NSCLC: Report on Lung-MAP SWOG S1400 (IASLC.org) - "The primary objective of this study was to establish an infrastructure that could be used to efficiently evaluate targeted therapies in biomarker subgroups. The infrastructure created allowed for biomarker testing and evaluation of targeted therapies with regulatory intent. Patients included in this trial had stage IV or recurrent squamous cell lung cancer and had received previous platinum-doublet chemotherapy."

Biomarker • Online posting

Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol. (PubMed, Lancet Oncol) - P2/3 | "Lung-MAP (S1400) met its goal to quickly address biomarker-driven therapy questions in squamous non-small-cell lung cancer. In early 2019, a new screening protocol was implemented expanding to all histological types of non-small-cell lung cancer and to add focus on immunotherapy combinations for anti-PD-1 and anti-PD-L1 therapy-relapsed disease. With these changes, Lung-MAP continues to meet its goal to focus on unmet needs in the treatment of advanced lung cancers."

Biomarker • Clinical • IO biomarker • Journal • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • HRD • PIK3CA

Targeted Therapy Approaches for MET Abnormalities in Non-Small Cell Lung Cancer. (PubMed, Drugs) - "Following the discovery of MET as a potential therapeutic target, extensive clinical studies have proposed three approaches to targeting MET: (1) MET tyrosine kinase inhibitors (TKIs), including crizotinib, capmatinib, tepotinib, savolinitib, and cabozantinib; (2) MET or HGF monoclonal antibodies, including emibetuzumab and ficlatuzumab; and (3) MET or HGF antibody drug conjugates, including telisotuzumab. Herein, we discuss the relevant clinical trials, particularly focusing on the efficacy as well as the safety and tolerability of the treatment options, in the promising field of targeting MET in NSCLC."

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

Phase 1 study of telisotuzumab vedotin in Japanese patients with advanced solid tumors. (PubMed, Cancer Med) - P1 | "In conclusion, telisotuzumab vedotin demonstrated a manageable safety profile, with antitumor activity in Japanese patients with advanced solid tumors; the recommended phase 2 dose was confirmed as 2.7 mg/kg every 3 weeks. ClinicalTrials.gov registration number: NCT03311477."

Clinical • Journal • P1 data • Oncology • Pain • Solid Tumor

Biotherapeutic Antibodies for the Treatment of Head and Neck Cancer: Current Approaches and Future Considerations of Photothermal Therapies. (PubMed, Front Oncol) - "There are currently three approved antibodies against HNCs (cetuximab, nivolumab, and pembrolizumab), and 48 antibodies under development...In addition, three antibody drug conjugates (ADCs: telisotuzumab-vedotin, indatuximab-ravtansine, and W0101) and two bispecific antibodies (GBR 1372 and ABL001) have been under development...These conjugates combine the high specificity of antibodies with unique spectral properties of GNPs to generate a treatment approach known as photothermal therapy. This approach can provide promising outcomes due to the ability of GNPs to convert light into heat, which can specifically destroy cancer cells and treat HNC in an effective manner."

Journal • Review • Developmental Disorders • Head and Neck Cancer • Infectious Disease • Oncology • Solid Tumor

"Interesting that just today $ABBV mentioned telisotuzumab vedotin (cMet ADC) $SGEN" (@JacobPlieth)

A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753). (PubMed, Clin Lung Cancer) - P2 | "Telisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC."

Clinical • Journal • P2 data • Bronchopulmonary Dysplasia • Hematological Disorders • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • Squamous Cell Carcinoma

Study of ABT-700 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=124; Active, not recruiting; Sponsor: AbbVie (prior sponsor, Abbott); Trial primary completion date: Dec 2015 ➔ Apr 2016

Trial primary completion date • Biosimilar • Oncology

Phase 1 Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients With Advanced Solid Tumors. (PubMed, Mol Cancer Ther) - "Among patients with nonamplified tumors (n=35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors."

Clinical • Journal • P1 data