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

AbbVie

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors Cancer

Treatments: Drug: ABBV-181; Drug: ABBV-368

Study type: Interventional

Funder types: Industry

Identifiers

NCT03071757

M16-074

2016-004205-14 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 139 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

139 participants in 5 patient groups

Part 1A: Monotherapy Dose Escalation

Experimental group

Description:

Part 1A: ABBV-368 (various dose levels) intravenous administration every 2 weeks (Q2W). One cycle of treatment is 28 days, thus there will be 2 doses with ABBV-368 per cycle.

Treatment:

Drug: ABBV-368

Part 2A: Monotherapy Cohort Expansion

Experimental group

Description:

Part 2A: Additional participants (triple negative breast cancer \[TNBC\]) will be enrolled in a dose expansion cohort that will further evaluate ABBV-368 (various dose levels) intravenous administration Q4W.

Treatment:

Drug: ABBV-368

Part 2B: Combination Therapy Cohort Expansion

Experimental group

Description:

Part 2B: Additional participants (with Head and Neck carcinoma) will be enrolled in a dose expansion cohort that will further evaluate ABBV-368 (various dose levels) intravenous administration Q4W plus ABBV-181.

Treatment:

Drug: ABBV-181

Drug: ABBV-368

Part 3A: 18F-AraG Imaging Substudy in TNBC Participants

Experimental group

Description:

Part 3A: Additional participants (with TNBC) will be enrolled in 18F-AraG Imaging Substudy that will further evaluate ABBV-368 intravenous administration Q4W plus ABBV-181.

Treatment:

Drug: ABBV-181

Drug: ABBV-368

Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants

Experimental group

Description:

Part 3B: Additional participants (with HNSCC) will be enrolled in 18F-AraG Imaging Substudy that will further evaluate ABBV-368 intravenous administration Q4W plus ABBV-181.

Treatment:

Drug: ABBV-181

Drug: ABBV-368