The primary purpose of this Phase 1, open-label study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of ABBV-368 as a monotherapy and in combination with ABBV-181 in participants with locally advanced or metastatic solid tumors. The study will consist of 2 parts: ABBV-368 dose escalation and ABBV-368 tumor-specific dose expansion (triple negative breast cancer [TNBC] cohort and head and neck cancer cohort).
|First Received Date||March 2, 2017|
|Last Changed Date||August 28, 2018|
|Start Date||March 27, 2017|
|Anticipated Primary Completion Date||February 15, 2019|
|Primary Outcome Measures||
Terminal half-life (t1/2) of ABBV-368 [Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period]
Area under the serum concentration-time curve (AUC) of ABBV-368 [Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period]
Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with ABBV-181 [Time Frame: Up to 1 year]
Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 [Time Frame: Up to 18 months]
Time to Cmax (Tmax) of ABBV-368 [Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period]
Terminal phase elimination rate constant (β) of ABBV-368 [Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period]
Number of Participants With Adverse Events [Time Frame: From first dose of study drug until 100 days following last dose of study drug (up to 24 months)]
Maximum observed serum concentration (Cmax) of ABBV-368 [Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period]
|Secondary Outcome Measures||
Objective Response Rate (ORR) [Time Frame: Up to 30 days after a 24-month of treatment period]
Clinical benefit rate (CBR) [Time Frame: Up to 30 days after a 24-month of treatment period]
Duration of Objective Response (DOR) [Time Frame: Up to 30 days after a 24-month of treatment period]
Progression-Free Survival (PFS) [Time Frame: Up to 30 days after a 24-month of treatment period]
|Study Arms / Comparison Groups||3 / 0|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
ABBVIE CALL CENTER
- Participants must have histologic or cytology diagnosis of a known immunogenic solid tumor, as described for Part 1 Dose Escalation and Part 2 Cohort Expansion:
- Part 1 Dose Escalation:
- Participants with advanced or metastatic solid tumors that have exhausted standard treatment for their incurable disease and for whom there is currently no programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) approved therapy, with immunogenic type tumors such as, but not limited to triple negative breast cancer (TNBC), ovarian cancer, small cell lung cancer, mesothelioma, and cholangiocarcinoma.
- Participants who are refractory to a PD-1/PD-L1 agent, with tumor types such as melanoma, NSCLC, platinum-pretreated head and neck cancer, second line bladder and RCC.
- Part 2A and 2B Cohort Expansion:
- 2A : TNBC ABBV-368 monotherapy cohorts: Subjects with locally advanced or metastatic TNBC that have exhausted standard treatment for their incurable disease.
- 2B : Head and Neck cohort: Participants with recurrent squamous cell head and neck carcinoma that are not candidates for curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
- Participants must have immune-related Response Evaluation Criteria for Solid Tumors (iRECIST) evaluable or measurable disease in the PART 1 and measurable disease per iRECIST in PART 2
- Adequate bone marrow, kidney and liver function.
- Received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 21 days prior to the first dose of ABBV-368.
- Prior treatment with an OX40 targeting agent.
- has known uncontrolled metastases to the central nervous system (CNS).
- History of active autoimmune disorders and other conditions that compromise or impair the immune system.
- Confirmed positive test results for human immunodeficiency virus (HIV), or subjects with chronic or active hepatitis B or C. Subjects who have a history of hepatitis B or C who have documented cures after anti-viral therapy may be enrolled.
- Has received live vaccine within 28 days prior to the first dose of study drug.
|Verification Date||August 2018|