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 nivolumab 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 (non-small cell lung cancer [NSCLC] cohort and head and neck cancer cohort) .
|First Received Date||March 2, 2017|
|Last Changed Date||April 28, 2017|
|Start Date||April 3, 2017|
|Anticipated Primary Completion Date||February 15, 2019|
|Primary Outcome Measures||
Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with nivolumab [Time Frame: Up to 1 year]
Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with nivolumab [Time Frame: Up to 18 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]
Time to Cmax (Tmax) 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]
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]
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]
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)]
|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]
Progression-Free Survival (PFS) [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]
|Study Arms / Comparison Groups||4 / 0|
|Ages||18 Years - 99 Years|
|Accepts Healthy Volunteers||No|
- 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:
- Parts 1A and 1B Dose Escalation:
- 1A: Subjects with advanced or metastatic solid tumors that have exhausted standard treatment for their incurable disease and who may be treatment naïve to a programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) targeting agent and for which there is no anti-PD-1/PD-L1 agent approved. Additional tumor types for which there is approved PD-1/PD-L1 therapy may be considered at the Sponsor's discretion provided they have failed such therapy in the past.
- 1B: Subjects for whom there is approved PD-1/PD-L1 targeting agent who are treatment-naïve to a PD-1/PD-L1 targeting agent; subjects for whom there is currently no PD-1/PD-L1 approved therapy and are diagnosed with immunogenic type tumors (eligible tumor types to be discussed with the sponsor); subjects who have been treated with a PD1/PD-L1 targeting agent and are refractory to such agent.
- Part 2A and 2B Cohort Expansion:
- Non Small Cell Lung Cancer (NSCLC): Participants with locally advanced or metastatic NSCLC who have failed platinum-based therapy and a PD-1/PD-L1 targeting agent. Participants with known genomic tumor aberrations for which there is approved targeted therapy should have disease progression on these therapies prior to receiving ABBV-368.
- 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. Tumor progression or recurrence must have occurred within 6 months of last dose of platinum therapy. Participants must be treatment- naïve to a PD-1/PD-L1 targeting agent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
- Subject must have immune-related Response Evaluation Criteria for Solid Tumors (irRECIST) evaluable or measurable disease in the PART 1 and measurable disease per irRECIST 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 or active autoimmune disorders and other conditions that compromise or impair the immune system.
- Active bacterial, fungal or viral infection including hepatitis B (HBV) or hepatitis C (HCV).
|Verification Date||April 2017|