A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors

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 ]. The MTD of ABBV-368 when administered as monotherapy or as combination therapy with nivolumab will be determined during the dose escalation phase of the study.
• Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with nivolumab [ Time Frame: Up to 18 months ]. Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with nivolumab will be established during the Dose expansion of the study
• 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 ]. Maximum observed serum concentration of ABBV-368
• Time to Cmax (Tmax) of ABBV-368 [ Time Frame: Day 1 Cycle 1 up to 30 days after a 24-month of treatment period ]. Time to Cmax of ABBV-368
• 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 ]. Area under the serum concentration-time curve of ABBV-368
• 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 phase elimination rate constant of ABBV-368
• 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 ]. Terminal half-life of ABBV-368
• 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) ]. An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization , results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.

Secondary Outcome Measures

• Objective Response Rate (ORR) [ Time Frame: 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.
• Clinical benefit rate (CBR) [Time Frame: 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.
• Progression-Free Survival (PFS) [Time Frame: Up to 30 days after a 24-month of treatment period]
  PFS time is defined as the time from the first dose of study drug (Day 1) to disease progression or death, whichever occurs first.
• Duration of Objective Response (DOR) [ Time Frame: 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.

Eligibility

Inclusion Criteria

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.

Exclusion Criteria

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).