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

Telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with fluorouracil, leucovorin, and budigalimab in locally advanced/metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (a/m GEA). (ASCO 2025) - P1, P2 | "Treatment is administered until disease progression, intolerable toxicity, or other discontinuation criteria are met. Either archived formalin-fixed paraffin-embedded tissue or a fresh biopsy is required for biomarker research that will include evaluation of c-Met protein expression and MET genomic alterations."

Combination therapy • IO biomarker • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • HER-2 • MET • PD-L1

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

Phase 1b/2 study evaluating telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with budigalimab in patients (pts) with advanced non-squamous (NSQ) non-small cell lung cancer (NSCLC) with no prior treatment for advanced disease and no actionable genomic alterations. (ASCO 2025) - P1, P1/2 | "Pts are randomized 1:1:1:1 to Temab-A at 1 of 2 doses determined in part 1 + budigalimab, to budigalimab + CT, or to SOC (pembrolizumab + CT) arms...Treatment continues until disease progression, intolerable toxicity, or other discontinuation criteria are met. The first dosing of the first patient enrolled is planned in March 2025."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • PD-L1

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

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

Telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced EGFR-mutated (MT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase 1 study. (ASCO 2025) - P1 | "Temab-A has a manageable safety profile with promising clinical activity in pts with 3L+ NSQ EGFR MT NSCLC, meriting further investigation. aConfirmed responses. P, probability."

Clinical • Metastases • P1 data • Anemia • Interstitial Lung Disease • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • MET

AndroMETa-Lung-713: A phase 2/3 study of telisotuzumab adizutecan (ABBV-400, Temab-A) vs standard of care (SOC) in patients with epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC). (ASCO 2026) - P1, P2/3 | "Clinical Trial Registration Number: NCT07155187 Background: Patients with advanced EGFR-mutated NSCLC routinely receive third-generation EGFR TKIs in first-line therapy, such as osimertinib or lazertinib, either as monotherapy or in combination with other agents. Following progression, available options primarily include platinum-doublet chemotherapy or amivantamab + chemotherapy, with country-specific approvals for additional agents including antibody-drug conjugates (ADCs)...Tumor assessments are performed Q6W for 2 years, then Q12W. Assessment of PK, immunogenicity, and exploratory biomarker analyses, including c-Met protein expression levels and ctDNA dynamics, will be conducted."

Clinical • First-in-human • P2/3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Phase I Study of Telisotuzumab Adizutecan (Temab-A, ABBV-400), a Novel c-Met Antibody-Drug Conjugate, in Patients With Late-Line Colorectal Cancer and Advanced Solid Tumors. (PubMed, J Clin Oncol) - P1 | "Temab-A at 2.4 mg/kg once every 3 weeks has a tolerable and manageable safety profile, with promising antitumor activity."

First-in-human • Journal • P1 data • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • BRAF • MET

Targeting MET-LGR5 crosstalk using an antibody-drug conjugate combination with diverse payloads to overcome adaptive resistance in colorectal cancer (AACR 2026) - "Combination treatment with ABT700-PBD and 8E11-CPT2 in CRC patient-derived xenograft models extended survival compared to single-agent ADCs. Collectively, our findings support MET and LGR5 ADC combination therapy as a novel treatment strategy to overcome adaptive resistance-driven relapse in CRC."

ADC • Colorectal Cancer • Oncology • Solid Tumor • LGR5 • STAT3

Telisotuzumab adizutecan (Temab-A, ABBV-400), a novel c-Met antibody-drug conjugate, in Asian patients (pts) with advanced CRC: Results of a phase I study (ESMO Asia 2025) - P1 | "Temab-A monotherapy had encouraging efficacy in AS pts with CRC with comparable responses to OVR pts. No new safety signals were observed vs OVR pts."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • MET

Lineage-Specific c-MET Expression and Co-Activated Pathway Signatures across Solid Tumors: Implications for Antibody– Drug Conjugate Therapy (AMP 2025) - "The recent U.S. Food and Drug Administration approval of telisotuzumab, a c-MET–targeted antibody–drug conjugate (ADC), for the treatment of lung adenocarcinoma has reignited interest in c-MET–directed therapeutics across other solid tumors... This pan-cancer proteogenomic analysis highlights significant heterogeneity in c-MET expression and downstream signaling across solid tumors. The integration of c-MET protein levels co-activated signaling pathways, and somatic mutation profiles may provide a more refined framework for patient stratification in future c-MET–targeted therapeutic trials. Whereas lung adenocarcinoma presents an ideal model for c-MET adenocarcinoma response, extending efficacy to other tumor types will likely require a multi-dimensional approach that accounts for proteomic context and oncogenic co-dependencies."

Colorectal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • MET • mTOR • STAT3

Telisotuzumab adizutecan (ABBV-400; Temab-A) monotherapy vs trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer with increased c-Met protein expression: An open-label, randomized, phase 3 trial. (ASCO 2025) - P1, P3 | "Patient eligibility includes age ≥18 years, confirmed c-Met expression of 3+ in ≥10% of tumor cells, metastatic adenocarcinoma of the colon/rectum, measurable disease per RECIST v1.1, ECOG performance status 0–1, prior treatment with a fluoropyrimidine (eg, 5-FU or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF antibody (unless locally not approved) or an anti-EGFR antibody if indicated, and appropriate targeted therapy or immunotherapy if targetable mutations present (eg, BRAF V600E or HER2) or MSI-H/dMMR. Prior treatment with regorafenib and/or fruquintinib is permitted, but no prior treatment with trifluridine/tipiracil Study-specific c-Met protein expression IHC cutoff is defined as 3+ intensity in ≥10% of tumor cells...Safety evaluations include adverse event monitoring, vital sign measurements, ECG variables, and clinical laboratory testing. Enrollment began in December 2024."

Clinical • IO biomarker • Metastases • Monotherapy • P3 data • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • HER-2 • MET • MSI

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

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."

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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