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)

A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV 324 in Adults With Hepatocellular Cancer or Squamous Cell Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Cancer; Squamous-Cell Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: ABBV-324; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Nanfang Hospital - Southern Medical University /ID# 276916
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital Fudan University /ID# 276917
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus /ID# 270604
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center-Hebrew University /ID# 271235
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center. /ID# 271236
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 270585
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Recruiting
      • Kansai Medical University Hospital /ID# 272884
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital /ID# 270583
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Completed
    • Fdi Clinical Research /ID# 272960
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 272718
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro /ID# 272719
• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital /ID# 270593
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center /ID# 270526
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope - Orange County Lennar Foundation Cancer Center /ID# 276120
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center /ID# 271573
    • Orange, California, United States, 92868-3201
      • Recruiting
      • UC Irvine Medical Center /ID# 270507
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA - Santa Monica /ID# 275995
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center /ID# 270517
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University /ID# 275757
  • New York
    • New York, New York, United States, 10021-3459
      • Recruiting
      • Memorial Sloan Kettering Cancer Center /ID# 271228
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Sidney Kimmel Cancer Center /ID# 276269
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners /ID# 272750

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation: ABBV-324; Participants will receive escalating doses of ABBV-324 as part of the approximately 6.5 year study duration.	Drug: ABBV-324; Intravenous (IV) Infusion
Experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 1; Participants will receive ABBV-324 dose 1 as part of the approximately 6.5 year study duration.	Drug: ABBV-324; Intravenous (IV) Infusion
Experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 2; Participants will receive ABBV-324 dose 2 as part of the approximately 6.5 year study duration.	Drug: ABBV-324; Intravenous (IV) Infusion
Experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 3; Participants will receive ABBV-324 dose 3 as part of the approximately 6.5 year study duration.	Drug: ABBV-324; Intravenous (IV) Infusion
Active Comparator: Part 2 Comparator Arm 4: Lenvatinib; Participants will receive lenvatinib as part of the approximately 6.5 year study duration.	Drug: Lenvatinib; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-324	AUC of ABBV-324.	Up to Approximately 4 Years
Maximum Observed Serum Concentration (Cmax) of ABBV-324	Cmax of ABBV-324.	Up to Approximately 4 Years
Time to Maximum Observed Serum Concentration (Tmax) of ABBV-324	Tmax of ABBV-324.	Up to Approximately 4 Years
Terminal Elimination Half-Life (t1/2) of ABBV-324	t1/2 of ABBV-324.	Up to Approximately 4 Years
Antidrug Antibody (ADA)	Incidence and concentration of anti-drug antibodies.	Up to Approximately 4 Years
Neutralizing Antidrug Antibody (nADA)	Incidence and concentration of neutralizing anti-drug antibodies.	Up to Approximately 4 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 5, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HCC; Lenvatinib; Hepatocellular Cancer; Squamous-Cell Non-Small Cell Lung Cancer; LUSC; ABBV-324
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Liver Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; lenvatinib
• Other Study ID Numbers: M25-292; 2024-518012-39 (Other Identifier: EU CT); 2024-518012-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No