Colorectal Cancer
Conditions
Keywords
Colorectal Cancer, CRC, Telisotuzumab Adizutecan (ABBV-400), Unresectable Locally Advanced/Metastatic CRC
Brief summary
Colorectal cancer (CRC) is the third most common type of cancer diagnosed worldwide and in China. The purpose of this study is to assess adverse events and how telisotuzumab adizutecan moves through the body of adult participants with unresectable locally advanced/metastatic CRC. Telisotuzumab adizutecan is an investigational drug being developed for the treatment of CRC. Study doctors put the participants in cohorts called treatment arms. Each treatment arm receives a different dose of telisotuzumab adizutecan. This study will include a dose escalation phase followed by a dose expansion phase. Up to approximately 30 adult participants with unresectable locally advanced/metastatic CRC, will be enrolled in the study in approximately 8 sites in China. In the dose escalation arms, participants will receive escalating doses of intravenously (IV) infused telisotuzumab adizutecan dose A or B. In dose expansion arm part 1, participants will receive dose A of IV infused telisotuzumab adizutecan. In dose expansion arm part 2, participants will receive the dose C of IV infused telisotuzumab adizutecan. The total study duration will be approximately 2.5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Interventions
Intravenous (IV) Infusion
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. * Has histologically or cytologically confirmed unresectable advanced/metastatic colorectal cancer (mCRC). * Has measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1. * Does not harbor the BRAF V600E mutation and is not deficient mismatch repair (dMMR)+/microsatellite instability (MSI)-High. * Stage 2 only: * Archival or recently obtained tumor material must be submitted for assessment of c-Met protein levels by an AbbVie designated IHC laboratory during the pre-screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed. If archival tissue is negative for c-Met protein expression with 3+ intensity, \>= 10% tumor cells, recently obtained biopsy material may be submitted for reassessment of c-Met protein expression with 3+ intensity, \>= 10% tumor cells.
Exclusion criteria
* History (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis. * Prior systemic regimen containing c-Met protein targeting antibody (e.g., amivantamab-vmjw, ABT-700) or define: antibody-drug conjugate (ADC). Tyrosine kinase inhibitors (TKIs) of Met protein are allowed. * History of Interstitial lung disease (ILD)/pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan. * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. * History of clinically significant, intercurrent lung-specific illnesses including, but not limited to: * Underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, dependence on supplemental oxygen, etc.) * Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) and prior pneumonectomy. * No resolution of any acute clinically significant treatment-related toxicity from prior therapy to Grade \<= 1 prior to study entry, except for neutropenia (Grade \<= 2), peripheral neuropathy (Grade \<= 2), and alopecia (any grade). * Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). * History of other malignancies within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year Overall Survival \[OS\] rate \> 90%).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unconjugated Payload of Telisotuzumab Adizutecan | Up to 24 Months | Unconjugated payload of telisotuzumab adizutecan. |
| Dose-Limiting Toxicity (DLT) of Telisotuzumab Adizutecan in Stage 1 | Up to 24 Months | DLTs are defined as grade \>= 3 thrombocytopenia that cannot clinically improve after adequate medical treatment/support, febrile neutropenia grade \>= 3 or grade 4 neutropenia that cannot clinically improve after adequate medical treatment/support, and any grade 2 or higher interstitial lung disease (ILD)/pneumonitis that cannot clinically improve after adequate medical treatment/support. |
| Maximum observed plasma or serum concentration (Cmax) of Telisotuzumab Adizutecan Conjugate | Up to 24 Months | Cmax of telisotuzumab adizutecan conjugate. |
| Time to Cmax (Tmax) of Telisotuzumab Adizutecan Conjugate | Up to 24 Months | Tmax of telisotuzumab adizutecan conjugate. |
| Area Under the Concentration-Time Curve (AUC) of Telisotuzumab Adizutecan Conjugate | Up to 24 Months | AUC of telisotuzumab adizutecan conjugate. |
| Total Antibody of Telisotuzumab Adizutecan | Up to 24 Months | Total antibody of telisotuzumab adizutecan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | Up to 24 Months | DoR as assessed by Investigator: DoR is defined as the time from the participantt's initial response (CR or PR) to the first occurrence of radiographic progression or death from any cause. |
| Best Overall Response (BOR) | Up to 24 Months | Disease control as assessed by the Investigator: BOR of confirmed CR or confirmed PR, or stable disease based on RECIST, version 1.1. |
| Progression-Free Survival (PFS) | Up to 24 Months | PFS as assessed by Investigator: PFS is defined as the time from the participant's first dose of study treatment until radiographic progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 24 Months | OS is defined as the time from the participant's first dose of study treatment until death from any cause. |
| Objective Response (OR) | Up to 24 Months | OR as assessed by the Investigator: Confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. |
Countries
China
Contacts
Primary ContactABBVIE CALL CENTER
Outcome results
None listed