A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors
- Registration Number
- NCT02955251
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 ABBV-428 ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Arm A, B, and C ABBV-428 Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428. Arm 2 ABBV-428 ABBV-428 plus nivolumab. Arm 2 Nivolumab ABBV-428 plus nivolumab. Arm D ABBV-428 Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab. Arm D Nivolumab Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.
- Primary Outcome Measures
Name Time Method 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 1 day of study drug administration within the 28-day cycle at the designated cohort dose 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.
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 Up to 2 years 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.
Time to Cmax (Tmax) of ABBV-428 Up to 30 days after a 24-month treatment period
- Secondary Outcome Measures
Name Time Method Duration of Objective Response (DOR) Up to 30 days after a 24-month of treatment period DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Clinical benefit rate (CBR) Up to 30 days after a 24-month of treatment period 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.
Progression-Free Survival (PFS) Up to 30 days after a 24-month of treatment period PFS time is defined as the time from the first dose of ABBV-428 to disease progression or death, whichever occurs first
Objective Response Rate (ORR) Up to 30 days after a 24-month of treatment period ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
Trial Locations
- Locations (15)
Centre Leon Berard /ID# 168072
🇫🇷Lyon CEDEX 08, Rhone, France
Gustave Roussy /ID# 162257
🇫🇷Villejuif, Ile-de-France, France
HonorHealth Research Institute - Pima /ID# 155461
🇺🇸Scottsdale, Arizona, United States
Institut Curie /ID# 162258
🇫🇷Paris CEDEX 05, Ile-de-France, France
Institut Bergonie /ID# 202391
🇫🇷Bordeaux, Gironde, France
National Taiwan Univ Hosp /ID# 169034
🇨🇳Taipei City, Taipei, Taiwan
Greenville Hospital System /ID# 154437
🇺🇸Greenville, South Carolina, United States
Hopital de la Timone /ID# 162256
🇫🇷Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, France
Northern Cancer Institute /ID# 163132
🇦🇺St Leonards, New South Wales, Australia
UC Davis Comprehensive Cancer Center - Main /ID# 154439
🇺🇸Sacramento, California, United States
University of Chicago /ID# 154440
🇺🇸Chicago, Illinois, United States
Fox Chase Cancer Center /ID# 170665
🇺🇸Philadelphia, Pennsylvania, United States
South Texas Accelerated Research Therapeutics /ID# 154442
🇺🇸San Antonio, Texas, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 154441
🇺🇸Houston, Texas, United States
Chris O'Brien Lifehouse /ID# 163131
🇦🇺Camperdown, New South Wales, Australia