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 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.
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.
Trial Locations
- Locations (15)
HonorHealth Research Institute - Pima /ID# 155461
🇺🇸Scottsdale, Arizona, United States
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
Greenville Hospital System /ID# 154437
🇺🇸Greenville, South Carolina, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 154441
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics /ID# 154442
🇺🇸San Antonio, Texas, United States
Chris O'Brien Lifehouse /ID# 163131
🇦🇺Camperdown, New South Wales, Australia
Northern Cancer Institute /ID# 163132
🇦🇺St Leonards, New South Wales, Australia
Institut Bergonie /ID# 202391
🇫🇷Bordeaux, Gironde, France
Scroll for more (5 remaining)HonorHealth Research Institute - Pima /ID# 155461🇺🇸Scottsdale, Arizona, United States