A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors

A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors

This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-428 when administered as monotherapy or in combination with nivolumab in participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-428; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse /ID# 163131
    • St Leonards, New South Wales, Australia, 2065
      • Northern Cancer Institute /ID# 163132
• France
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Institut Bergonie /ID# 202391
  • Ile-de-France
    • Paris CEDEX 05, Ile-de-France, France, 75248
      • Institut Curie /ID# 162258
    • Villejuif, Ile-de-France, France, 94805
      • Gustave Roussy /ID# 162257
  • Provence-Alpes-Cote-d Azur
    • Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, France, 13385
      • Hopital de la Timone /ID# 162256
  • Rhone
    • Lyon CEDEX 08, Rhone, France, 69373
      • Centre Leon Berard /ID# 168072
• Taiwan
  • Taipei
    • Taipei City, Taipei, Taiwan, 10002
      • National Taiwan Univ Hosp /ID# 169034
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258-2345
      • HonorHealth Research Institute - Pima /ID# 155461
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center - Main /ID# 154439
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • University of Chicago /ID# 154440
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center /ID# 170665
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System /ID# 154437
  • Texas
    • Houston, Texas, United States, 77030-4000
      • MD Anderson Cancer Center at Texas Medical Center /ID# 154441
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics /ID# 154442

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies.
• Participants have adequate bone marrow, renal, hepatic and coagulation function.
• For all dose expansion arms, participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
• Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.

Exclusion Criteria:

• Active or prior documented autoimmune disease in the last 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
• History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
• Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis B or C. Participants who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled.
• Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy.
• Male participants who are considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle).	Drug: ABBV-428; ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.
Experimental: Arm A, B, and C; Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428.	Drug: ABBV-428; ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.
Experimental: Arm D; Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.	Drug: ABBV-428; ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.; Drug: Nivolumab; Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.; Other Names: OPDIVO
Experimental: Arm 2; ABBV-428 plus nivolumab.	Drug: ABBV-428; ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.; Drug: Nivolumab; Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.; Other Names: OPDIVO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events		First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose
Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab	If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.	1 day of study drug administration within the 28-day cycle at the designated cohort dose
Area under the serum concentration-time curve (AUC) of ABBV-428		Up to 30 days after a 24-month treatment period
Terminal half-life (t1/2) of ABBV-428		Up to 30 days after a 24-month treatment period
Maximum observed serum concentration (Cmax) of ABBV-428		Up to 30 days after a 24-month treatment period
Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab	The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.	Up to 2 years
Time to Cmax (Tmax) of ABBV-428		Up to 30 days after a 24-month treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Objective Response (DOR)	DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.	Up to 30 days after a 24-month of treatment period
Clinical benefit rate (CBR)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment.	Up to 30 days after a 24-month of treatment period
Progression-Free Survival (PFS)	PFS time is defined as the time from the first dose of ABBV-428 to disease progression or death, whichever occurs first	Up to 30 days after a 24-month of treatment period
Objective Response Rate (ORR)	ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.	Up to 30 days after a 24-month of treatment period

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Luke JJ, Barlesi F, Chung K, Tolcher AW, Kelly K, Hollebecque A, Le Tourneau C, Subbiah V, Tsai F, Kao S, Cassier PA, Khasraw M, Kindler HL, Fang H, Fan F, Allaire K, Patel M, Ye S, Chao DT, Henner WR, Hayflick JS, McDevitt MA, Fong L. Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. J Immunother Cancer. 2021 Feb;9(2):e002015. doi: 10.1136/jitc-2020-002015.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2016
• Primary Completion (Actual): October 29, 2019
• Study Completion (Actual): October 29, 2019

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 17, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Nivolumab; Ovarian cancer; Non-small cell lung cancer (NSCLC); Neoplasm; Advanced solid tumor; Non-squamous NSCLC
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: M15-819; 2016-001461-88 (EudraCT Number)

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