A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-324 in Adult Participants With Hepatocellular Cancer (HCC) or Squamous-Cell Non-Small Cell Lung Cancer (LUSC)

NCT06858813 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: M25-2922024-518012-392024-518012-39-00
• Study Type: interventional
• Target: 232
• Locations: 7 countries
• Sites: 22

Brief Summary

HCC is a common cancer worldwide and a leading cause of cancer-related death. Lung cancer is the most frequently diagnosed cancer in the world, and the leading cause of cancer deaths. The purpose of this study is to assess adverse events and change in disease activity when ABBV-324 is given to adult participants to treat hepatocellular cancer (HCC) or squamous-cell non-small cell lung cancer (LUSC). ABBV-324 is an investigational drug being developed for the treatment of HCC and LUSC. Study doctors put the participants in groups called arms. Each arm receives ABBV-324 alone (monotherapy) or a comparator drug, lenvatinib followed by a safety follow-up period. Approximately 232 HCC or LUSC will be enrolled in the study in approximately 45 sites worldwide. In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of ABBV-324 until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will receive ABBV-324, or a comparator of oral lenvatinib. The study will run for a duration of approximately 6.5 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.

Conditions

Hepatocellular Cancer; Squamous-Cell Non-Small Cell Lung Cancer

Keywords

Hepatocellular Cancer; Squamous-Cell Non-Small Cell Lung Cancer; LUSC; HCC; ABBV-324; Lenvatinib

Outcome Measures

Primary Outcomes (5)

• Number of Participants with Adverse Events (AE)s

  An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

  Up to Approximately 4 Years

• Number of Participants with Change in Vital Signs

  Number of Participants with Change in Vital Signs will be assessed.

  Up to Approximately 4 Years

• Number of Participants with Change in Electrocardiogram (ECG)

  Number of Participants with Change in ECG will be assessed.

  Up to Approximately 4 Years

• Number of Participants with Change in Clinical Laboratory Tests

  Number of participants with change in clinical laboratory tests will be assessed.

  Up to Approximately 4 Years

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants with a confirmed Complete Response or partial response(PR) per investigator review according to response evaluation criteria in solid tumors (RECIST) version 1.1.

  Up to Approximately 4 Years

Secondary Outcomes (6)

• Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-324

  Up to Approximately 4 Years

• Maximum Observed Serum Concentration (Cmax) of ABBV-324

  Up to Approximately 4 Years

• Time to Maximum Observed Serum Concentration (Tmax) of ABBV-324

  Up to Approximately 4 Years

• Terminal Elimination Half-Life (t1/2) of ABBV-324

  Up to Approximately 4 Years

• Antidrug Antibody (ADA)

  Up to Approximately 4 Years

Study Arms (5)

Part 1 Dose Escalation: ABBV-324

EXPERIMENTAL

Participants will receive escalating doses of ABBV-324 as part of the approximately 6.5 year study duration.

Drug: ABBV-324

Part 2 Dose Optimization Arm 1: ABBV-324 Dose 1

EXPERIMENTAL

Participants will receive ABBV-324 dose 1 as part of the approximately 6.5 year study duration.

Drug: ABBV-324

Part 2 Dose Optimization Arm 1: ABBV-324 Dose 2

EXPERIMENTAL

Participants will receive ABBV-324 dose 2 as part of the approximately 6.5 year study duration.

Drug: ABBV-324

Part 2 Dose Optimization Arm 1: ABBV-324 Dose 3

EXPERIMENTAL

Participants will receive ABBV-324 dose 3 as part of the approximately 6.5 year study duration.

Drug: ABBV-324

Part 2 Comparator Arm 4: Lenvatinib

ACTIVE COMPARATOR

Participants will receive lenvatinib as part of the approximately 6.5 year study duration.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Oral Capsule

Part 2 Comparator Arm 4: Lenvatinib

ABBV-324 DRUG

Intravenous (IV) Infusion

Part 1 Dose Escalation: ABBV-324; Part 2 Dose Optimization Arm 1: ABBV-324 Dose 1; Part 2 Dose Optimization Arm 1: ABBV-324 Dose 2; Part 2 Dose Optimization Arm 1: ABBV-324 Dose 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Hepatocellular cancer (HCC) only: Child-Pugh A classification within 7 days before Cycle 1, Day 1 dosing.
• Laboratory values meeting the criteria outlined in the protocol.
• QT interval corrected for heart rate (QTc) \< 470 msec (using Fridericia's correction), no Grade 3 arrythmia, and no other clinically significant cardiac abnormalities.
• Measurable disease per RECIST version 1.1.
• Part 1 and Part 2 - participants with HCC meeting the following disease activity criteria:
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or cytology. Participants with fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma/HCC are not eligible to enroll.
• Disease that is not amenable to surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies. For participants who progressed after locoregional therapy for HCC, locoregional therapy must have been completed \>= 28 days prior to baseline scan for the current study.
• Part 1: Failure of at least 1 prior systemic treatment for HCC.
• Part 2: Failure of at least 1 prior systemic treatment consisting of an immune checkpoint inhibitor (CPI) containing regimen for HCC, including but not limited to, atezolizumab in combination with bevacizumab or tremelimumab in combination with durvalumab. Note: Participants who have received prior lenvatinib will not be eligible for Part 2.
• Part 1 only - participants with squamous-cell non-small cell lung cancer (LUSC) meeting the following disease activity criteria:
• Advanced or metastatic LUSC that is not amenable to surgical resection.
• Must have failed at least 1 prior line of therapy that included at least platinum-based chemotherapy and an immune CPI, and/or an appropriate targeted therapy (if applicable), or is not suitable for other approved therapeutic options that have demonstrated clinical benefit at the judgment of the investigator. Participants should have no more than 2 lines of prior cytotoxic chemotherapy excluding neoadjuvant and/or adjuvant. Participants who are intolerant of standard therapy are eligible.

You may not qualify if:

• Unresolved clinically significant adverse events (AEs) \> Grade 1 from prior anticancer therapy except for alopecia.
• 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). Participants may continue with antiepileptic therapy if required.
• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or 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 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.
• Must have discontinued anticancer therapy with antineoplastic intent including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half lives of the drug (whichever is shorter) prior to the first dose of ABBV-324. Palliative radiation therapy for bone, skin or subcutaneous metastases with 10 fractions or less is permitted and not participant to a washout period.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (22)

City of Hope National Medical Center /ID# 270526

Duarte, California, 91010, United States

RECRUITING

City of Hope - Orange County Lennar Foundation Cancer Center /ID# 276120

Irvine, California, 92618, United States

RECRUITING

USC Norris Comprehensive Cancer Center /ID# 271573

Los Angeles, California, 90033, United States

RECRUITING

UC Irvine Medical Center /ID# 270507

Orange, California, 92868-3201, United States

RECRUITING

UCLA - Santa Monica /ID# 275995

Santa Monica, California, 90404, United States

RECRUITING

University of Chicago Medical Center /ID# 270517

Chicago, Illinois, 60637, United States

RECRUITING

Washington University /ID# 275757

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center /ID# 271228

New York, New York, 10021-3459, United States

RECRUITING

Thomas Jefferson University Sidney Kimmel Cancer Center /ID# 276269

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

SCRI Oncology Partners /ID# 272750

Nashville, Tennessee, 37203, United States

RECRUITING

Nanfang Hospital - Southern Medical University /ID# 276916

Guangzhou, Guangdong, 510000, China

RECRUITING

Zhongshan Hospital Fudan University /ID# 276917

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Rambam Health Care Campus /ID# 270604

Haifa, 3109601, Israel

RECRUITING

Hadassah Medical Center-Hebrew University /ID# 271235

Jerusalem, 91120, Israel

RECRUITING

Rabin Medical Center. /ID# 271236

Petah Tikva, 4941492, Israel

RECRUITING

National Cancer Center Hospital East /ID# 270585

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

Kansai Medical University Hospital /ID# 272884

Hirakata-shi, Osaka, 573-1191, Japan

RECRUITING

National Cancer Center Hospital /ID# 270583

Chuo-Ku, Tokyo, 104-0045, Japan

RECRUITING

Fdi Clinical Research /ID# 272960

San Juan, 00927, Puerto Rico

COMPLETED

Hospital Universitario Fundacion Jimenez Diaz /ID# 272718

Madrid, 28040, Spain

RECRUITING

Hospital Universitario HM Sanchinarro /ID# 272719

Madrid, 28050, Spain

RECRUITING

National Taiwan University Hospital /ID# 270593

Taipei, 100, Taiwan

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Liver Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 5, 2025
• Study Start: April 14, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2); US (10); IL (3); ES (2); JP (3); PR (1); TW (1)