Clinical trial NCT06464692: 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
Official title: A Phase 1b Study to Evaluate Safety and Pharmacokinetics (PK) of Telisotuzumab Adizutecan (ABBV-400) in Chinese Subjects With Unresectable Locally Advanced/Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer
CRC
Telisotuzumab Adizutecan (ABBV-400)
Unresectable Locally Advanced/Metastatic CRC
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%).

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT) of Telisotuzumab Adizutecan in Stage 1
timeFrame: Up to 24 Months
measure: Maximum observed plasma or serum concentration (Cmax) of Telisotuzumab Adizutecan Conjugate
timeFrame: Up to 24 Months
measure: Time to Cmax (Tmax) of Telisotuzumab Adizutecan Conjugate
timeFrame: Up to 24 Months
measure: Area Under the Concentration-Time Curve (AUC) of Telisotuzumab Adizutecan Conjugate
timeFrame: Up to 24 Months
measure: Total Antibody of Telisotuzumab Adizutecan
timeFrame: Up to 24 Months
measure: Unconjugated Payload of Telisotuzumab Adizutecan
timeFrame: Up to 24 Months
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: Up to 24 Months
measure: Duration of Response (DoR)
timeFrame: Up to 24 Months
measure: Best Overall Response (BOR)
timeFrame: Up to 24 Months
measure: Progression-Free Survival (PFS)
timeFrame: Up to 24 Months
measure: Overall Survival (OS)
timeFrame: Up to 24 Months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital /ID# 263297
state: Beijing
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University /ID# 263309
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital /ID# 263049
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital /ID# 263172
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital /ID# 263248
state: Hubei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University /ID# 263193
state: Jiangxi
city: Shenyang
country: China
facility: First Affiliated Hospital of China Medical University /ID# 263338
state: Liaoning
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine /ID# 263094
state: Zhejiang
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: