Study to Assess Adverse Events and How Intravenously (IV) Infused ABBV-400 Moves Through the Body of Adult Participants With Unresectable Locally Advanced/Metastatic Colorectal Cancer

AbbVie

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Colorectal Cancer

Treatments: Drug: ABBV-400

Study type: Interventional

Funder types: Industry

Identifiers

NCT06464692

M24-559

Details and patient eligibility

About

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 ABBV-400 moves through the body of adult participants with unresectable locally advanced/metastatic CRC.

ABBV-400 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 ABBV-400. This study will include a dose escalation phase to determine the best dose of ABBV-400, followed by a dose expansion phase to confirm the dose. Up to approximately 27 adult participants with unresectable locally advanced/metastatic CRC, will be enrolled in the study in approximately 10 sites in China.

In the dose escalation arms, participants will receive escalating doses of intravenously (IV) infused ABBV-400 dose A or B. In dose expansion arm part 1, participants will receive the optimal dose of IV infused ABBV-400. In dose expansion arm part 2, participants will receive the dose B of IV infused ABBV-400. 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.

Enrollment: 27 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

• Expansion Part 2 only:

  • Diagnosis of a malignant solid tumor by histology (World Health Organization [WHO] criteria).
  • Measurable disease per RECIST v1.1.
  • Advanced solid tumors including (but not limited to) non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastroesophageal junction adenocarcinoma (GEA), colorectal cancer (CRC), and renal cell carcinoma (RCC), who have progressed on standard of care therapy and are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.

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 targeting antibody (e.g., amivantamab-vmjw, ABT-700) or define: antibody-drug conjugate (ADC). Tyrosine kinase inhibitors (TKIs) of Met are allowed.

• No availability of representative baseline tumor tissue (archived and/or fresh biopsy during screening phase), only applicable for participants enrolled in Stage 2.

• 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%).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

27 participants in 4 patient groups

Safety Run-In Cohort 1: ABBV-400 Dose A

Experimental group

Description:

Participants with unresectable locally advanced/metastatic colorectal cancer (CRC) will receive ABBV-400 dose A during the approximately 2.5 year study duration.

Treatment:

Drug: ABBV-400

Safety Run-In Cohort 2: ABBV-400 Dose B

Experimental group

Description:

Participants with unresectable locally advanced/metastatic CRC will receive ABBV-400 dose B during the approximately 2.5 year study duration.

Treatment:

Drug: ABBV-400

Dose Expansion Part 1: ABBV-400 Optimal Dose

Experimental group

Description:

Participants with unresectable locally advanced/metastatic CRC will receive ABBV-400 at the optimal dose during the approximately 2.5 year study duration.

Treatment:

Drug: ABBV-400

Dose Expansion Part 2: ABBV-400 Dose B

Experimental group

Description:

If further analysis is warranted, participants with unresectable locally advanced/metastatic CRC will receive ABBV-400 dose B during the approximately 2.5 year study duration.

Treatment:

Drug: ABBV-400