Trial: A Randomized Trial Assessing Adverse Ev…

Trial Details

Sponsor: AbbVie (industry)

Phase: 3

Start date: Nov. 8, 2024

Planned enrollment: 460

Trial ID: NCT06614192

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: ABBV-400 (telisotuzumab)

Overview

ABBV-400 (telisotuzumab adizutecan; sometimes “Temab-A”) is an investigational, c‑Met–targeting antibody–drug conjugate (ADC) being developed for multiple solid tumors. Human trials are ongoing, including a first‑in‑human phase 1 study (NCT05029882) and subsequent signal‑seeking and randomized studies across tumor types. Early clinical activity has been reported in metastatic colorectal cancer (mCRC) and in non‑small cell lung cancer (NSCLC). (ascopubs.org)

Mechanism of action

Target: c‑Met (MET receptor tyrosine kinase). The antibody component is telisotuzumab.
Payload: a novel topoisomerase‑1 inhibitor (adizutecan) linked via a cleavable valine–alanine linker; the conjugation uses a bromoacetamide attachment designed to minimize systemic payload release.
Rationale: leverages c‑Met expression to deliver a potent Topo‑1 inhibitor to tumor cells, aiming for activity even at lower c‑Met expression levels and in settings where MMAE‑based c‑Met ADCs have had limitations. (aacrjournals.org)

Efficacy

Metastatic colorectal cancer (monotherapy, phase 1; NCT05029882) - As of the October 2023 data cut, among 122 treated patients (dose escalation plus CRC‑specific expansion), objective response rates (ORR) by dose cohort were: - 1.6 mg/kg Q3W: 0% (n=32) - 2.4 mg/kg Q3W: 15% (6/40) - 3.0 mg/kg Q3W: 20% (8/41) - Median duration of response: 4.1 months at 2.4 mg/kg and 5.5 months at 3.0 mg/kg (data immature).
- Median PFS: 5.3 months (2.4 mg/kg) and 4.5 months (3.0 mg/kg) (data immature).
- Responses were enriched at higher c‑Met expression (reported >30% ORR at efficacious doses ≥2.4 mg/kg), with some activity at lower expression levels (approximately 10–15% ORR). (ascopubs.org)

ctDNA‑based translational readouts in mCRC (phase 1; NCT05029882) - In 113 evaluable patients, confirmed ORR was 18%. Molecular response in ctDNA (≥50% decrease in circulating tumor fraction by Guardant panels) correlated with higher ORR (about 35% with molecular response vs 0–8% without) and longer PFS. (ascopubs.org)

NSCLC (phase 1; NCT05029882) - Preliminary antitumor activity has been reported in previously treated EGFR‑wild‑type, non‑squamous NSCLC, presented at ESMO 2024. (dailyreporter.esmo.org)

Planned/ongoing studies - A multicohort phase 1b “signal‑seeking” trial (NCT06084481) is enrolling across additional solid tumors (e.g., HCC, PDAC, BTC, ESCC, breast, HNSCC). (ascopubs.org) - A randomized phase 3 trial in refractory, c‑Met–overexpressing mCRC compares ABBV‑400 monotherapy to trifluridine/tipiracil plus bevacizumab (NCT06614192). A separate, large phase 2 master protocol in mCRC is evaluating combinations with FOLFOX/bevacizumab or 5‑FU/leucovorin/panitumumab (e.g., NCT06820463). (jhoonline.biomedcentral.com)

Safety

Phase 1 (mCRC cohorts; cut as of October 2023; N=122) - Any grade ≥3 treatment‑emergent adverse event (TEAE): 64%; serious TEAEs: 41%.
- Common hematologic TEAEs: anemia 52% (grade ≥3: 30%), neutropenia 37% (≥3: 25%), leukopenia 25% (≥3: 12%), thrombocytopenia 23% (≥3: 12%).
- Common non‑hematologic TEAEs: nausea 57% (≥3: 3%), fatigue 43% (≥3: 2%), vomiting 39% (≥3: 4%).
- Diarrhea grade ≥3: <1%.
- Unadjudicated interstitial lung disease/pneumonitis: 7% (grade ≥3: 2%).
- Treatment‑related discontinuations: 9%.
Dose levels of 2.4–3.0 mg/kg Q3W showed “tolerable and manageable” profiles, with better long‑term tolerability noted at 2.4 mg/kg. The maximum tolerated dose reported for subsequent evaluations was 3.0 mg/kg Q3W. (ascopubs.org)

Preclinical/targeted toxicology - Non‑clinical studies indicated expected Topo‑1–class toxicities (bone marrow and gastrointestinal) in cynomolgus monkeys. (aacrjournals.org)

Key details and development status

Modality: c‑Met–directed IgG1 ADC carrying a novel Topo‑1 inhibitor payload (adizutecan). (aacrjournals.org)
Dosing under study: Q3W intravenous dosing; evaluated 1.6–6.0 mg/kg in phase 1; dose expansion commonly at 2.4 or 3.0 mg/kg Q3W; MTD 3.0 mg/kg Q3W. (ascopubs.org)
Indications under active study: mCRC (monotherapy and combinations), NSCLC (various molecular subsets), and multiple additional solid tumors in signal‑seeking cohorts. (ascopubs.org)

HealthScout AI Analysis

Goal: To compare the efficacy, safety, and patient-reported outcomes of ABBV-400 monotherapy versus trifluridine/tipiracil (LONSURF) plus bevacizumab in adults with c-Met over-expressed refractory metastatic colorectal cancer, and to select the optimal ABBV-400 dose for phase 3 evaluation.

Patients: Adults with refractory metastatic colorectal cancer characterized by c-Met over-expression, ECOG performance status 0–1, measurable disease by RECIST v1.1, and life expectancy ≥12 weeks. Key exclusions include prior c-MET–targeting antibodies or ADCs, hypersensitivity to bevacizumab or trifluridine/tipiracil, and active infections per protocol.

Design: Global, open-label, randomized, controlled, two-stage phase 3 study across ~160 sites in 15–20 countries, totaling ~460 participants. Stage 1 randomizes participants to two ABBV-400 dose levels to characterize safety, PK, and antitumor activity and select the optimal dose. Stage 2 randomizes participants to the optimal ABBV-400 dose versus standard of care LONSURF plus bevacizumab. Blinded independent central review is used for key efficacy endpoints.

Treatments: ABBV-400 monotherapy: ABBV-400 (telisotuzumab adizutecan) is a c-Met–targeting antibody-drug conjugate linking telisotuzumab to a cleavable topoisomerase I inhibitor payload. It selectively delivers cytotoxic payload to c-Met–overexpressing tumor cells to inhibit DNA replication. Early-phase studies in solid tumors, including colorectal cancer, showed objective response rates around 18–24% at 2.4–3.0 mg/kg, with higher responses (>35%) in tumors with higher c-Met expression; safety has been manageable but includes myelosuppression, GI toxicities, and a risk of ILD/pneumonitis, with better tolerability at 2.4 mg/kg relative to 3.0 mg/kg. Standard of care comparator: oral trifluridine/tipiracil plus IV bevacizumab, a commonly used regimen in refractory mCRC that provides disease control and survival benefit over trifluridine/tipiracil alone.

Outcomes: Primary outcomes include, in Stage 1, safety and tolerability (AEs, vital signs, ECGs, and laboratory abnormalities) and objective response by BICR; and in Stage 2, objective response by BICR and overall survival. Key secondary outcomes include PFS by BICR and investigator, OS in Stage 1, duration of response, disease control rate, and investigator-assessed ORR. Stage 1 includes extensive pharmacokinetics of ABBV-400 (Cmax, Tmax, t1/2, AUC), ADC analytes, unconjugated payload, and immunogenicity (ADA, nADA). Stage 2 includes patient-reported outcomes using EORTC QLQ-C30 domains (physical function, diarrhea, global health status/quality of life) at prespecified cycle days.

Burden on patient: Moderate to high. Participants will have frequent clinic visits for IV therapy (ABBV-400 or bevacizumab infusions) and safety monitoring, along with regular imaging per RECIST. Stage 1 adds substantial burden from intensive pharmacokinetic sampling, immunogenicity testing, and comprehensive safety labs and ECGs to support dose selection. While the SOC arm includes an oral component, the addition of bevacizumab requires infusion visits and monitoring. Overall, the schedule exceeds typical standard care due to centralized radiology review timing, serial PRO questionnaires, and expanded safety/PK assessments, particularly in Stage 1.

Last updated: Oct 2025

Eligibility

Show Criteria

No email / No phone

Status: Completed

AndroMETa-CRC-064: An Open Label, Randomized, Controlled, Global Phase 3 Study Comparing ABBV-400 Monotherapy to LONSURF (Trifluridine and Tipiracil) Plus Bevacizumab in Subjects With c-Met Over-Expressed Refractory Metastatic Colorectal Cancer

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: ABBV-400 (telisotuzumab)

Overview

Mechanism of action

Efficacy

Safety

Key details and development status

Further reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (51)

Mater Hospital Brisbane /ID# 268360

Assuta Medical Center /ID# 267745

Hadassah Medical Center-Hebrew University /ID# 267579

Rabin Medical Center /ID# 267740

Rambam Health Care Campus /ID# 267739

Tel Aviv Sourasky Medical Center /ID# 267578

The Chaim Sheba Medical Center /ID# 267741

Aichi Cancer Center /ID# 268237

National Cancer Center Hospital East /ID# 268236

The University of Osaka Hospital /ID# 268743

Saitama Prefectural Cancer Center /ID# 268706

National Cancer Center Hospital /ID# 268713

Pan American Center for Oncology Trials /ID# 267888

Seoul National University Bundang Hospital /ID# 268592

Asan Medical Center /ID# 268717

Samsung Medical Center /ID# 268720

Seoul National University Hospital /ID# 268719

Yonsei University Health System Severance Hospital /ID# 268718

Changhua Christian Hospital /ID# 270464

China Medical University Hospital /ID# 267631

Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 267635

Linkou Chang Gung Memorial Hospital /ID# 267637

National Cheng Kung University Hospital /ID# 270468

Taichung Veterans General Hospital /ID# 270467

Taipei Veterans General Hospital /ID# 267628

Kaohsiung Chang Gung Memorial Hospital /ID# 267638

National Taiwan University Hospital /ID# 267627

City of Hope - Orange County Lennar Foundation Cancer Center /ID# 270655

City of Hope National Medical Center /ID# 267875

USC Norris Comprehensive Cancer Center /ID# 268131

Lutheran Medical Center- Cancer Centers of Colorado /ID# 268175

Yale New Haven Hospital /ID# 269125

AdventHealth Orlando /ID# 267970

Winship Cancer Institute of Emory University /ID# 266884

St. Luke's Cancer Institute: Boise /ID# 268095

Hope And Healing Cancer Services /ID# 268541

Northwestern Memorial Hospital /ID# 268610

Springfield Clinic - First /ID# 268666

Community Cancer Center North /ID# 267965

Hattiesburg Clinic /ID# 267860

Washington University /ID# 267872

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 268185

Rutgers Cancer Institute of New Jersey /ID# 268056

Duke University Medical Center /ID# 267966

University of North Carolina Medical Center /ID# 266879

Avera Cancer Institute - Sioux Falls /ID# 268074

West Cancer Center and Research Institute - Germantown /ID# 268619

The University of Texas MD Anderson Cancer Center /ID# 268098

University of Texas - Southwestern Medical Center /ID# 268241

University of Virginia /ID# 268108

Millennium Research & Clinical Development /ID# 268400