NCT02955251

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2016

Typical duration for phase_1

Geographic Reach
4 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 4, 2016

Completed
14 days until next milestone

Study Start

First participant enrolled

November 18, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 29, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 29, 2019

Completed
Last Updated

July 20, 2020

Status Verified

July 1, 2020

Enrollment Period

2.9 years

First QC Date

November 2, 2016

Last Update Submit

July 17, 2020

Conditions

Keywords

CancerNeoplasmAdvanced solid tumorNivolumabNon-small cell lung cancer (NSCLC)Non-squamous NSCLCOvarian cancer

Outcome Measures

Primary Outcomes (7)

  • 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 Outcomes (4)

  • Duration of Objective Response (DOR)

    Up to 30 days after a 24-month of treatment period

  • Clinical benefit rate (CBR)

    Up to 30 days after a 24-month of treatment period

  • Progression-Free Survival (PFS)

    Up to 30 days after a 24-month of treatment period

  • Objective Response Rate (ORR)

    Up to 30 days after a 24-month of treatment period

Study Arms (4)

Arm 1

EXPERIMENTAL

ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle).

Drug: ABBV-428

Arm A, B, and C

EXPERIMENTAL

Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428.

Drug: ABBV-428

Arm D

EXPERIMENTAL

Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.

Drug: ABBV-428Drug: Nivolumab

Arm 2

EXPERIMENTAL

ABBV-428 plus nivolumab.

Drug: ABBV-428Drug: Nivolumab

Interventions

ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.

Arm 1Arm 2Arm A, B, and CArm D

Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.

Also known as: OPDIVO
Arm 2Arm D

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

HonorHealth Research Institute - Pima /ID# 155461

Scottsdale, Arizona, 85258-2345, United States

Location

UC Davis Comprehensive Cancer Center - Main /ID# 154439

Sacramento, California, 95817, United States

Location

University of Chicago /ID# 154440

Chicago, Illinois, 60637-1443, United States

Location

Fox Chase Cancer Center /ID# 170665

Philadelphia, Pennsylvania, 19111, United States

Location

Greenville Hospital System /ID# 154437

Greenville, South Carolina, 29605, United States

Location

MD Anderson Cancer Center at Texas Medical Center /ID# 154441

Houston, Texas, 77030-4000, United States

Location

South Texas Accelerated Research Therapeutics /ID# 154442

San Antonio, Texas, 78229, United States

Location

Chris O'Brien Lifehouse /ID# 163131

Camperdown, New South Wales, 2050, Australia

Location

Northern Cancer Institute /ID# 163132

St Leonards, New South Wales, 2065, Australia

Location

Institut Bergonie /ID# 202391

Bordeaux, Gironde, 33000, France

Location

Hopital de la Timone /ID# 162256

Marseille, Provence-Alpes-Côte d'Azur Region, 13385, France

Location

Centre Leon Berard /ID# 168072

Lyon, Rhone, 69373, France

Location

Institut Curie /ID# 162258

Paris, Île-de-France Region, 75248, France

Location

Gustave Roussy /ID# 162257

Villejuif, Île-de-France Region, 94805, France

Location

National Taiwan Univ Hosp /ID# 169034

Taipei City, Taipei, 10002, Taiwan

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

NeoplasmsCarcinoma, Non-Small-Cell LungOvarian Neoplasms

Interventions

ABBV-428Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteLung DiseasesRespiratory Tract DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • AbbVie Inc.

    AbbVie

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 2016

First Posted

November 4, 2016

Study Start

November 18, 2016

Primary Completion

October 29, 2019

Study Completion

October 29, 2019

Last Updated

July 20, 2020

Record last verified: 2020-07

Data Sharing

IPD Sharing
Will not share

Locations