Advanced Solid Tumors Cancer
Conditions
Keywords
Cancer, Neoplasm, Advanced solid tumor, Nivolumab, Non-small cell lung cancer (NSCLC), Non-squamous NSCLC, Ovarian cancer
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.
Interventions
DRUGABBV-428
ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.
DRUGNivolumab
Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cmax (Tmax) of ABBV-428 | Up to 30 days after a 24-month treatment period | — |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, France, Taiwan, United States
Outcome results
None listed