telisotuzumab adizutecan (ABBV-400) / AbbVie - LARVOL DELTA

A Study to Assess Intravenous (IV) Telisotuzumab Adizutecan in Combination With Fluorouracil, Folinic Acid, and Oxaliplatin (FOLFOX) Compared to Standard of Care in Adult Participants With First-Line Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P2/3 | N=900 | Not yet recruiting | Sponsor: AbbVie

New P2/3 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A phase 2 randomized study comparing telisotuzumab adizutecan monotherapy with standard of care in patients with post-adjuvant circulating tumor DNA-positive colorectal cancer. (ASCO-GI 2026) - P1, P2 | "Study follow-up will occur every 3 mos for the first 2 yrs and every 6 mos for the 3 yrs thereafter. The Table shows study objectives and endpoints."

Circulating tumor DNA • Clinical • Monotherapy • P2 data • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MET • TOP1

A Study to Assess Adverse Events, Change in Disease Activity of Intravenous Telisotuzumab Adizutecan in Combination With Osimertinib as First-Line Treatment in Adult Participants With Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=854 | Recruiting | Sponsor: AbbVie | Trial completion date: Dec 2031 ➔ Nov 2036 | Trial primary completion date: Dec 2031 ➔ Nov 2036

Adverse events • 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

Phase I basket study of telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein-targeting antibody-drug conjugate: Results from patients (pts) with pancreatic ductal adenocarcinoma (PDAC) (ESMO 2025) - P1 | "Table: 2214MO Outcome Overall (N=42 ‡ ) 1L FOLFIRINOX (n=26) 1L gem– nab -paclitaxel (n=15) Best overall response,* ,† n (%) CR 0 0 0 PR 10 (24) 4 (15) 6 (40) SD 24 (57) 17 (65) 6 (40) PD 4 (10) 2 (8) 2 (13) NE/Not assessed 4 (10) 3 (12) 1 (7) ORR,* ,† n (%) 10 (24) 4 (15) 6 (40) CBR,* ,† n (%) 34 (81) 21 (81) 12 (80) Median PFS, mo [95% CI] 5.3 [4.0, 6.8] 5.0 [3.6, 6.2] 6.8 [2.4, NE] *Confirmed responses...CBR, clinical benefit rate; CR, complete response; NE, not estimable; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. Conclusions Temab-A had a manageable safety profile in pts with advanced PDAC and promising efficacy, especially in pts who received 1L gemcitabine– nab -paclitaxel."

Clinical • P1 data • Pan tumor • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MET

Telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Dose expansion results of a phase I study (ESMO 2025) - P1 | "Methods Unselected pts with advanced CRC were enrolled in 2 parts: (1) Safety lead-in: pts received escalating doses of Temab-A at 1.6 (n=7) or 2.4 (n=8) mg/kg (2.0 mg/kg backfill [n=5]) + Bev 7.5 mg/kg Q3W; (2) Dose optimization: pts were randomized to Temab-A 2.0 (n=23) or 2.4 (n=22) mg/kg + Bev 7.5 mg/kg Q3W, or trifluridine/tipiracil (TAS-102) 35 mg/m 2 days 1–5 and 8–12 Q4W + Bev 5.0 mg/kg (n=21) Q2W (SOC). c, confirmed; CI, confidence interval; DCR, disease control rate; DCR12, DCR at 12 weeks; ORR, objective response rate. Conclusions Temab-A at 2.4 mg/kg + Bev had manageable safety and promising efficacy compared with the SOC in 3L+ pts with CRC."

Clinical • Combination therapy • P1 data • Colorectal Cancer • Oncology • Solid Tumor • MET

Telisotuzumab adizutecan (ABBV-400; Temab-A) in patients with MET-amplified (MET-amp) advanced solid tumors: Results from a phase I study (ESMO 2025) - P1 | "Table: 918O All pts with MET -amp tumors 1.6 mg/kg n=18 2.0 mg/kg n=8 2.4 mg/kg n=34 3.0 mg/kg n=39 Total ∗ N=100 Grade ≥3 AE, n (%) 10 (56) 4 (50) 24 (71) 33 (85) 72 (72) Gastrointestinal AEs, n (%) 14 (78) 5 (63) 27 (79) 29 (74) 75 (75) Grade ≥3 1 (6) 0 0 2 (5) 3 (3) Hematologic AE, n (%) 9 (50) 3 (38) 25 (74) 34 (87) 72 (72) Grade ≥3 5 (28) 3 (38) 19 (56) 28 (72) 56 (56) cORR, n (%) 7 (39) 3 (38) 16 (47) 20 (51) 46 (46) cCBR, n (%) 12 (67) 5 (63) 27 (79) 33 (85) 78 (78) *Includes 1 pt treated at 4 mg/kg.AE, adverse event; c, confirmed; CBR, clinical benefit rate; ORR, objective response rate. Conclusions Temab-A monotherapy had a manageable safety profile and encouraging efficacy in pts with diverse MET- amp advanced solid tumors."

Clinical • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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

Leveraging patient-derived organoids to investigate bystander effects of antibody-drug conjugates in solid tumor backgrounds (AACR 2026) - "Experimental assays incorporated mosaic PDO populations treated with ADCs (trastuzumab deruxtecan, telisotuzumab adizutecan, ADCs) and controls (antibody alone, warhead alone). PDO-based platforms combined with automated culture and advanced image analysis provide a robust system to study ADC bystander effects in heterogeneous tumor contexts. These findings will inform ADC development strategies and biomarker-driven patient selection."

ADC • Clinical • Oncology • Solid Tumor • HER-2 • 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

M25-287: A Study to Assess Adverse Events, Change in Disease Activity of Intravenous Telisotuzumab Adizutecan in Combination with Osimertinib as First-Line Treatment in Adult Participants with Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer (clinicaltrialsregister.eu) - P2/3 | N=44 | Recruiting | Sponsor: AbbVie Deutschland GmbH & Co. KG

Adverse events • New P2/3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

M25-713: A Study to Assess Adverse Events, Change in Disease Activity of Intravenous (IV) Telisotuzumab Adizutecan Compared to Standard of Care in Adult Participants with Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer (clinicaltrialsregister.eu) - P2/3 | N=56 | Recruiting | Sponsor: AbbVie Deutschland GmbH & Co. KG

Adverse events • New P2/3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

M24-064: A Study Assessing Adverse Events and Disease Activity When Comparing Intravenously (IV) Infused ABBV-400 to Trifluridine and Tipiracil (LONSURF) Oral Tablets Plus IV Infused Bevacizumab in Adult Participants with Refractory Metastatic Colorectal Cancer expressing c-Met Protein Level Above Cutoff (clinicaltrialsregister.eu) - P2/3 | N=87 | Not yet recruiting | Sponsor: AbbVie Deutschland GmbH & Co. KG

Adverse events • Monotherapy • New P2/3 trial • Colorectal Cancer • Oncology • Solid Tumor

A Phase 2/3 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination with Osimertinib as First-Line Treatment in Patients with Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer (ChiCTR) - P2/3 | N=688 | Not yet recruiting | Sponsor: Shanghai Chest Hospital; Shanghai Chest?Hospital

New P2/3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • MET

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

Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400 (clinicaltrials.gov) - P1 | N=302 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Platinum resistant • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Epithelial Ovarian Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2 • TOP1

Genomic alterations in circulating tumor DNA (ctDNA) and response to telisotuzumab adizutecan (ABBV-400) treatment in patients (pts) with colorectal cancer (CRC). (ASCO-GI 2025) - P1 | "Telisotuzumab adizutecan has promising efficacy. RRs were seen in CRC pts with heterogeneous genomic profiles, including pts positive for actionable biomarkers in the metastatic setting. More pts with MR experienced RRs and benefited from treatment."

Circulating tumor DNA • Clinical • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ASXL1 • BRAF • FGFR3 • FLT1 • HER-2 • KRAS • MET • NRG1 • PTPRT • SMAD4 • TP53

Dose optimization and exposure-response analyses to support optimal dose of ABBV-400, a novel C-met–targeting antibody drug conjugate, in patients with metastatic colorectal cancer (mCRC). (ASCO 2024) - P1 | "Population PK, E-R for efficacy and safety and RDI analyses and totality of clinical data supported the selection of 2.4 mg/kg Q3W as optimal ABBV-400 monotherapy dose for further study in mCRC patients. 1. Sharma M, et al."

Clinical • Metastases • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • MET • TOP1

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

Exposure-response analyses from a randomized dose optimization study of telisotuzumab adizutecan (Temab-A) in combination with bevacizumab in patients with metastatic colorectal cancer (mCRC). (ASCO-GI 2026) - P1 | " The ongoing phase 1 trial included a safety lead-in (Part 7a; 1.6 and 2.4 mg/kg every 3 weeks [Q3W] Temab-A+BEV) followed by a randomized dose optimization study evaluating two dose levels of Temab-A (Part 7b; 2.0 and 2.4 mg/kg Q3W) in combination with BEV and a third randomized arm evaluating standard of care (SOC); trifluridine/tipiracil+BEV; N=20) in patients with mCRC. Consistent strong ER relationships were demonstrated for Temab-A+BEV from an RDO study. These findings were similar to those from Temab-A monotherapy, which supported 2.4 mg/kg Q3W dosing in a cMet unselected mCRC population to provide good balance between efficacy and safety."

Clinical • Combination therapy • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

A phase 2 randomized study of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with standard of care (SOC) in patients with metastatic colorectal cancer. (ASCO-GI 2026) - P1, P2 | "During D-ESC, pts receive escalating doses of Temab-A (Q4W) with either FOLFOX + bevacizumab (BEV; substudy 1: N~18) or 5-fluorouracil (5-FU)–folinic acid + panitumumab (PAN; substudy 2: N~12) in 28-day cycles. Objectives and endpoints are listed in the table. CR, complete response; DOR, duration of response; Inv, investigator; OR, overall response; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; PROs, patient reported outcomes."

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

Study to Evaluate Adverse Events and Efficacy of Intravenous (IV) Telisotuzumab Adizutecan in Combination With a PD-1 Immune Checkpoint Inhibitor in Adult Participants With Advanced or Metastatic Non-Squamous NSCLC With No Prior Treatment for Advanced Disease, and No Actionable Genomic Alterations (clinicaltrials.gov) - P1/2 | N=252 | Recruiting | Sponsor: AbbVie | N=132 ➔ 252

Adverse events • Checkpoint inhibition • Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • PD-L1

A Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Telisotuzumab Adizutecan Compared to Standard of Care in Adult Participants With Locally Advanced or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=430 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2031 ➔ Sep 2030 | Trial primary completion date: Aug 2031 ➔ Sep 2030

Adverse events • Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

M24-311: Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unresectable Metastatic Colorectal Cancer in Combination With IV Fluorouracil, Folinic Acid, and Bevacizumab (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor