Sponsor: AbbVie (industry)
Phase: 2
Start date: Nov. 12, 2023
Planned enrollment: 280
ABBV-400 (telisotuzumab adizutecan) is an antibody-drug conjugate (ADC) that consists of telisotuzumab, a c-Met-targeting antibody, conjugated to a novel topoisomerase 1 inhibitor payload via a stable, cleavable linker [1]. The drug is designed to specifically target cells expressing c-Met (MET protein), which is frequently overexpressed in several types of cancer including non-small cell lung cancer (NSCLC), gastroesophageal cancer, and colorectal cancer (CRC). The topoisomerase 1 inhibitor payload works by interrupting DNA replication in cancer cells.
In a Phase 1 study (NCT05029882) of patients with advanced solid tumors, ABBV-400 has shown promising efficacy across multiple cancer types. In colorectal cancer (n=122), objective response rates of 18% and 24% were observed at doses of 2.4 mg/kg and 3.0 mg/kg respectively, with higher response rates (>35%) in patients with higher c-Met expression [2]. In NSCLC patients with EGFR wild-type disease (n=48), the objective response rate was 43.8% with a clinical benefit rate of 85.4% [3]. The drug has also shown activity in patients with MET-amplified tumors, with a 73% response rate reported in one cohort (n=11).
The safety profile has been generally manageable across trials. Common treatment-emergent adverse events include hematologic effects such as anemia (52-66%), neutropenia (37-62%), and thrombocytopenia (23-43%), as well as non-hematologic events including nausea (57-60%), fatigue (43-49%), and vomiting (38-39%) [1,3]. Grade 3 or higher adverse events occurred in 63-88% of patients across studies. Interstitial lung disease/pneumonitis has been reported in 6-9% of patients. The 2.4 mg/kg dose appears to have better long-term tolerability than 3.0 mg/kg, with higher relative dose intensity and generally lower adverse event rates [2].
[1] Phase 1 Results in Advanced Solid Tumors - Annals of Oncology [2] Latest Phase 1 Results in Colorectal Cancer - ASCO 2024 [3] Phase 1 Results in NSCLC - Annals of Oncology
Last updated: Dec 2024
Last updated: Aug 2025
Goal: To evaluate the safety, efficacy, and optimal dose of ABBV-400 in combination with fluorouracil, folinic acid, and bevacizumab, and to compare ABBV-400-containing regimens to standard of care in previously treated patients with unresectable metastatic colorectal cancer.
Patients: Adults with histologically or cytologically confirmed unresectable metastatic colorectal cancer who have measurable disease by RECIST 1.1 and have progressed on only one prior systemic first-line therapy. Patients with BRAF V600E mutations or with dMMR+/MSI-H tumors are excluded, as are those who have recently received prior anticancer therapies.
Design: This is a multicenter, randomized, phase 2 study with approximately 280 participants allocated to several dose-escalation and dose-optimization arms, including comparator standard of care cohorts. ABBV-400 is tested in combination with standard chemotherapeutic agents across multiple dosing schedules.
Treatments: ABBV-400, an investigational antibody-drug conjugate targeting c-Met, is being studied at various doses and schedules in combination with fluorouracil, folinic acid, and bevacizumab. ABBV-400 delivers a novel topoisomerase 1 inhibitor to c-Met expressing cancer cells, disrupting DNA replication. Early phase 1 studies showed objective response rates of 18-24% in colorectal cancer, with better responses (>35%) in tumors with higher c-Met expression, and a manageable safety profile mainly characterized by hematologic and gastrointestinal adverse events. The control arm uses a standard regimen of fluorouracil, folinic acid, bevacizumab, and irinotecan, which is standard second-line therapy for mCRC.
Outcomes: Primary endpoints include objective response rate (ORR) by RECIST v1.1, progression-free survival, and rate of adverse events. Secondary endpoints include duration of response, overall survival, and best overall response as defined by RECIST criteria.
Burden on patient: There is a moderate to high patient burden due to frequent intravenous treatments, regular clinic visits, ongoing laboratory and imaging assessments, and monitoring for adverse events. As this is a dose-finding study with a novel agent, participants can expect more clinic visits and tests than with standard of care, including safety labs, frequent physical exams, and likely additional blood draws for pharmacokinetic and biomarker analyses.
Inclusion Criteria:
* Diagnosis of histologically or cytologically confirmed unresectable metastatic colorectal cancer (mCRC).
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Progressed on only one first-line (1L) systemic treatment of combination chemotherapy in the metastatic setting with or without targeted therapy.
Exclusion Criteria:
* Harbor the BRAF V600E mutation.
* dMMR+/MSI-H.
* Received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-400.
Edegem, Antwerpen, 2650, Belgium
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Bonheiden, Antwerpen, 2820, Belgium
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Bruxelles, Bruxelles-Capitale, 1200, Belgium
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Gent, Oost-Vlaanderen, 9000, Belgium
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Leuven, Vlaams-Brabant, 3000, Belgium
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Roeselare, West-Vlaanderen, 8800, Belgium
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Anderlecht, 1070, Belgium
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Tübingen, Baden-Wuerttemberg, 72076, Germany
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Mannheim, Baden-Wuerttemberg, 68167, Germany
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Berlin, 13353, Germany
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Hamburg, 20246, Germany
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Kfar Saba, HaMerkaz, 4428164, Israel
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Jerusalem, Yerushalayim, 91120, Israel
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Jerusalem, Yerushalayim, 91031, Israel
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Tel Aviv, 6789140, Israel
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Haifa, 3109601, Israel
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Nagoya-shi, Aichi, 464-8681, Japan
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Kashiwa-shi, Chiba, 277-8577, Japan
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Chuo-ku, Tokyo, 104-0045, Japan
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Hwasun-gun, Jeonranamdo, 58128, Korea, Republic of
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Madrid, 28050, Spain
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Barcelona, 08035, Spain
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Madrid, 28041, Spain
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Valencia, 46010, Spain
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Zaragoza, 50009, Spain
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Kaohsiung City, Kaohsiung, 833, Taiwan
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Taipei City, Taipei, 100, Taiwan
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Taoyuan City, 333, Taiwan
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Kaohsiung, 807, Taiwan
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Tainan, 704, Taiwan
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Phoenix, Arizona, 85054, United States
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Springdale, Arkansas, 72762, United States
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Duarte, California, 91010, United States
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Irvine, California, 92618, United States
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New Haven, Connecticut, 06519, United States
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Jacksonville, Florida, 32224, United States
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Chicago, Illinois, 60611-2927, United States
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Indianapolis, Indiana, 46250-2042, United States
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Fort Wayne, Indiana, 46804, United States
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Henderson, Louisiana, 89052, United States
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Rochester, Minnesota, 55905-0001, United States
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Durham, North Carolina, 27710-3000, United States
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Charlotte, North Carolina, 28204, United States
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Portland, Oregon, 97239, United States
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Charleston, South Carolina, 29425, United States
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Sioux Falls, South Dakota, 57105, United States
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Houston, Texas, 77090-3063, United States
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Houston, Texas, 77030, United States
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Fairfax, Virginia, 22031, United States
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Fairfax, Virginia, 22031, United States
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