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

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

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

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=694 | Not yet recruiting | Sponsor: AbbVie

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

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

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

An oral presentation on investigational telisotuzumab adizutecan (ABBV-400, Temab-A), a next-generation, c-Met directed antibody-drug conjugate (ADC) with a novel topoisomerase 1 inhibitor (Top1i) payload, will showcase (PRNewswire) - P1 | N=520 | NCT05029882 | Sponsor: AbbVie | "Preliminary safety and efficacy results in 41 patients with pre-treated, advanced epidermal growth factor receptor (EGFR)-mutated non-squamous non-small cell lung cancer (NSCLC) from the dose expansion part of a Phase 1 study (NCT05029882). Patients received a median of 3 prior lines of therapies and 93% of patients had prior anti-EGFR treatment. The objective response rate (ORR) was 63%. High ORR was observed regardless of c-Met protein expression levels. At the time of data cut-off, 54% of responders experienced a ≥6 months duration of response (DoR). The most common any-grade TEAEs in ≥30% of patients were anemia (63%), nausea (61%), vomiting (37%), decreased appetite (34%), and neutropenia (34%). Additional data with 4 months follow-up will be presented at ASCO."

P1 data • Lung Non-Squamous Non-Small Cell Cancer

Antibody-drug Conjugate Pneumonitis in a Patient With Stage IV Adenocarcinoma of the Lung (ATS 2025) - "At presentation, he was receiving a C-Met ADC (telisotuzumab-adizutecan), with the most recent outpatient ECOG of 1...He was started on 3 liters/min of oxygen, ceftriaxone, and azithromycin...Empiric antibiotics were later escalated to cefepime and doxycycline, and due to worsening respiratory distress, transitioned to piperacillin-tazobactam, TMP-SMX, and fluconazole...Clinicians managing patients with advanced cancers on emerging therapies should consider drug-related pneumonitis as a potential diagnosis. Without a non-invasive diagnostic test, determining the appropriate timing for initiating high-dose corticosteroids and immunosuppressants presents a clinical challenge that necessitates further guidelines and education."

Clinical • Metastases • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumococcal Infections • Pneumonia • Pulmonary Embolism • Solid Tumor • MET

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 | Recruiting | Sponsor: AbbVie | N=206 ➔ 280

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

Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Adizutecan (ABBV-400) Moves Through the Body of Adult Participants With Unresectable Locally Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: AbbVie | Trial completion date: Apr 2027 ➔ Sep 2028 | Trial primary completion date: Apr 2027 ➔ Sep 2028

Adverse events • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

ABBV-969: A first-in-class dual-targeting PSMA-STEAP1 drug conjugate for the treatment of metastatic castrate-resistant prostate cancer (AACR 2025) - P1 | "ABBV-969 is a conjugate of the DVD-Ig with a proprietary topoisomerase-1 (Top1) inhibitor linker-drug identical to that used in two assets in clinical development, ABBV-400, targeting c-Met, and ABBV-706, targeting SEZ6. Furthermore, ABBV-969 is well tolerated in cynomolgus monkeys with bone marrow and gastrointestinal toxicities common to other Top1 inhibitor ADCs. ABBV-969 is currently in dose escalation in a Phase 1 clinical study (NCT06318273)."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • MET • SEZ6 • STEAP1 • TOP1

A Study to Evaluate the Adverse Events, Efficacy, and Optimal Dose of Intravenous (IV) Telisotuzumab Adizutecan in Combination With IV Budigalimab 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=172 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

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

A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid/Leucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=390 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

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

Evaluating ABBV-400 with fluorouracil, folinic acid, and bevacizumab in previously treated patients with mCRC (JSMO 2025) - No abstract available

Clinical • Colorectal Cancer • Oncology

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

Phase 1b study evaluating efficacy and safety of ABBV-400 in select advanced solid tumor indications (JSMO 2025) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor

Telisotuzumab Adizutecan (ABBV-400), a c-Met-Targeting ADC, in Pts With Advanced GEA: Results From a Phase 1 Study (JSMO 2025) - No abstract available

Clinical • Metastases • P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

ABBV-400, a novel c-Met-targeting antibody-drug conjugate, in advanced solid tumors: Results in colorectal cancer (JSMO 2025) - No abstract available

Metastases • Colorectal Cancer • Oncology • Solid Tumor • MET

M21-404: Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab (clinicaltrials.gov) - P1 | N=520 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid/Leucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=390 | Not yet recruiting | Sponsor: AbbVie

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

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

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

PK/PD analyses of circulating tumor DNA (ctDNA) in patients with metastatic colorectal cancer (mCRC) treated with telisotuzumab adizutecan (ABBV-400). (ASCO-GI 2025) - P1 | "Exposure-response analyses have previously shown correlation between ABBV-400 conjugate exposures and probability of efficacy (objective response rate) as well as safety in mCRC subjects. The current PK/PD analyses demonstrate that higher ABBV-400 conjugate and payload exposures are also correlated with liquid biopsy data, i.e., ctDNA and MR based on ctDNA. c-MET expression and MET-amp did not have impact on ABBV-400 exposures."

Circulating tumor DNA • Clinical • Metastases • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

Biomarkers of response in patients with gastric/gastroesophageal junction adenocarcinoma (GEA) treated with telisotuzumab adizutecan. (ASCO-GI 2025) - P1 | "In pts with advanced GEA treated with telisotuzumab adizutecan, c-Met OE/MET amp and ctDNA-based MR were associated with enhanced antitumor activity. Compared with real-world data, MET amp was enriched in this study population. Phase 2 studies will continue to explore c-Met OE and MET amp prevalence and their potential predictive value with other biomarkers in a clinically representative population."

Biomarker • Clinical • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

A Study to Evaluate the Adverse Events, Efficacy, and Optimal Dose of Intravenous (IV) Telisotuzumab Adizutecan in Combination With IV Budigalimab 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=172 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

AndroMETa-GEA: A Study to Evaluate the Adverse Events, Efficacy, and Optimal Dose of Intravenous (IV) ABBV-400 in Combination With IV Fluorouracil, Leucovorin, and Budigalimab in Adult Participants With Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Combination therapy • Enrollment open • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor