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

AbbVie139 enrolled

Overview

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 3 parts: ABBV-368 dose escalation, ABBV-368 tumor-specific dose expansion (triple negative breast cancer \[TNBC\] cohort and head and neck cancer cohort) and 18F-AraG Imaging Substudy.

Recruitment is closed in Part 1A; subjects are in maintenance

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

139

Conditions

Advanced Solid Tumors Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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: * 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. * Part 3A and 3B Imaging Substudy: * 3A: Participants with locally advanced or metastatic TNBC that have exhausted standard treatment for their incurable disease and are treatment naïve to a PD-1/PD-L1 targeting agent. * 3B: Participants with recurrent HNSCC that are not candidates for curative treatment with local or systemic therapy, or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. 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. * 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. 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 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 A, 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.

Locations (27)

Moores Cancer Center at UC San Diego /ID# 201334

La Jolla, California, United States

University of California, Davis Comprehensive Cancer Center /ID# 201342

Sacramento, California, United States

Stanford University /ID# 206949

Stanford, California, United States

Yale University /ID# 207895

New Haven, Connecticut, United States

Carolina BioOncology Institute /ID# 160786

Huntersville, North Carolina, United States

Outcomes

Primary Outcomes

Terminal half-life (t1/2) of ABBV-368

Terminal half-life of ABBV-368

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Area under the serum concentration-time curve (AUC) of ABBV-368

Area under the serum concentration-time curve of ABBV-368

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with ABBV-181

The MTD of ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study.

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

Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 will be established during the Dose expansion of the study

Time frame: Up to 18 months

Time to Cmax (Tmax) of ABBV-368

Time to Cmax of ABBV-368

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Terminal phase elimination rate constant (β) of ABBV-368

Terminal phase elimination rate constant of ABBV-368

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Number of Participants With Adverse Events

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.

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Maximum observed serum concentration (Cmax) of ABBV-368

Maximum observed serum concentration of ABBV-368

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Secondary Outcomes

Objective Response Rate (ORR)

ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Clinical benefit rate (CBR)

CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Duration of Objective Response (DOR)

DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination

Progression-Free Survival (PFS)

PFS time is defined as the time from the first dose of study drug (Day 1) to disease progression or death, whichever occurs first.

Time frame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination