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-181. This study will also evaluate the safety and tolerability of ABBV-181 in combination with Rovalpituzumab Tesirine. The study will consist of 2 parts: ABBV-181 monotherapy dose escalation and expansion, and ABBV-181 in combination with Rovalpituzumab Tesirine.
|First Received Date||December 15, 2016|
|Last Changed Date||July 19, 2018|
|Start Date||December 14, 2016|
|Anticipated Primary Completion Date||December 14, 2019|
|Primary Outcome Measures||
Recommended Phase 2 Dose (RPTD) and schedule for ABBV-181 and Rovalpituzumab Tesirine combination [Time Frame: Up to 6 months]
Terminal half-life (t1/2) [Time Frame: Up to 4 weeks after participant's first dose]
Maximum observed serum concentration (Cmax) [Time Frame: Up to 12 weeks after participant's first dose]
Area under the serum concentration time curve (AUC) [Time Frame: Up to 12 weeks after participant's first dose]
Number of participants with adverse events [Time Frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months)]
Time to Cmax (Tmax) [Time Frame: Up to 12 weeks after participant's first dose]
Recommended Phase 2 Dose (RPTD) for ABBV-181 [Time Frame: Up to 6 months]
Maximum tolerated dose (MTD) of ABBV-181 [Time Frame: Up to 6 months]
|Secondary Outcome Measures||
Objective response rate (ORR) [Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period]
Preliminary response and activity of ABBV-181 and Rovalpituzumab Tesirine when given in combination [Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period]
Clinical benefit rate (CBR, defined as CR, PR or SD) [Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period]
Progression-free survival (PFS) [Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period]
Duration of objective response (DOR) [Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period]
|Study Arms / Comparison Groups||2 / 0|
|Ages||18 Years - 99 Years|
|Accepts Healthy Volunteers||No|
ABBVIE CALL CENTER
- Participant must have an advanced solid tumor and must not be a candidate for surgical resection or other approved therapeutic regimen known to provide clinical benefit. For dose escalation, the participant may have been previously treated with a programmed cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be PD-I/PD-L1 targeting agent naïve. For Combination, the participant must be have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve.
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for Monotherapy and 0 to 1 for Combination.
- Participants have adequate bone marrow, renal, hepatic and coagulation function.
- Participants must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the trial. Participants in the expansion cohort must have measurable disease per RECIST version 1.1 or disease evaluable by assessment of tumor antigens.
- Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of ABBV-181 or Rovalpituzumab Tesirine.
- For Combination therapy, participant must not have had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based drug.
- Participant has unresolved adverse events greater than grade 1 from prior anticancer therapy except for alopecia.
- 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. Subjects who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA are anti-viral therapy may be enrolled.
- Participant has known history or inflammatory bowel disease, pneumonitis, or known uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).
|Verification Date||July 2018|