A Multicenter, Phase 1, Open-Label, Dose-Escalation 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

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

Sponsors

Lead sponsor: AbbVie

Source AbbVie
Brief Summary

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.

Detailed Description

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

Overall Status Recruiting
Start Date March 21, 2017
Completion Date September 29, 2021
Primary Completion Date June 15, 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Terminal half-life (t1/2) of ABBV-368 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 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 Up to 1 year
Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 Up to 18 months
Time to Cmax (Tmax) of ABBV-368 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 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 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 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 Outcome
Measure Time Frame
Objective Response Rate (ORR) 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) 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) 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) 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
Enrollment 170
Condition
Intervention

Intervention type: Drug

Intervention name: ABBV-368

Description: Intravenous infusion

Intervention type: Drug

Intervention name: ABBV-181

Description: Intravenous infusion

Eligibility

Criteria:

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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
AbbVie Inc. Study Director AbbVie
Overall Contact

Last name: ABBVIE CALL CENTER

Phone: 847.283.8955

Email: [email protected]

Location
facility status
Ucsd /Id# 201334 | La Jolla, California, 92093, United States Recruiting
UC Davis Comprehensive Cancer Center - Main /ID# 201342 | Sacramento, California, 95817, United States Recruiting
Stanford University /ID# 206949 | Stanford, California, 94305, United States Recruiting
Yale University /ID# 207895 | New Haven, Connecticut, 06510, United States Recruiting
University of Iowa Hospitals and Clinics /ID# 213170 | Iowa City, Iowa, 52242, United States Not yet recruiting
Carolina BioOncology Institute /ID# 160786 | Huntersville, North Carolina, 28078, United States Recruiting
Greenville Hospital System /ID# 160785 | Greenville, South Carolina, 29605, United States Recruiting
UT Southwestern Medical Center /ID# 201934 | Dallas, Texas, 75390-7208, United States Recruiting
South Texas Accelerated Research Therapeutics /ID# 160788 | San Antonio, Texas, 78229, United States Recruiting
University of Virginia /ID# 212895 | Charlottesville, Virginia, 22908, United States Not yet recruiting
Virginia Cancer Specialists /ID# 160787 | Fairfax, Virginia, 22031, United States Recruiting
Institut Curie /ID# 165038 | Paris CEDEX 05, Ile-de-France, 75248, France Recruiting
Hopital de la Timone /ID# 165036 | Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, 13385, France Recruiting
Centre Leon Berard /ID# 165037 | Lyon CEDEX 08, Rhone, 69373, France Recruiting
Institut Gustave Roussy /ID# 165035 | Villejuif, Val-de-Marne, 94800, France Recruiting
National Cancer Center Hospital East /ID# 214530 | Kashiwa-shi, Chiba, 277-8577, Japan Not yet recruiting
National Cancer Center Hospital /ID# 214531 | Chuo-ku, Tokyo, 104-0045, Japan Not yet recruiting
Pan American Center for Oncology Trials, LLC /ID# 213809 | Rio Piedras, 00935, Puerto Rico Recruiting
Hospital Duran i Reynals /ID# 205997 | L'Hospitalet de Llobregat, Barcelona, 08907, Spain Recruiting
Clinica Universitar de Navarra - Pamplona /ID# 208879 | Pamplona, Navarra, Comunidad, 31008, Spain Recruiting
Hospital General Universitario Gregorio Maranon /ID# 205999 | Madrid, 28007, Spain Recruiting
Clinica Universidad de Navarra - Madrid /ID# 205996 | Madrid, 28027, Spain Recruiting
Hospital Puerta de Hierro /ID# 206973 | Madrid, 28035, Spain Recruiting
Hospital Universitario Fundacion Jimenez Diaz /ID# 211500 | Madrid, 28040, Spain Recruiting
Hosp Clin Univ de Valencia /ID# 211499 | Valencia, 46010, Spain Recruiting
National Cheng Kung University Hospital /ID# 164002 | Tainan City, Tainan, 70403, Taiwan Recruiting
National Taiwan Univ Hosp /ID# 164000 | Taipei City, Taipei, 10002, Taiwan Recruiting
Taipei Medical University Hospital /ID# 164001 | Taipei City, 11031, Taiwan Recruiting
Location Countries

France

Japan

Puerto Rico

Spain

Taiwan

United States

Verification Date

November 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 5
Arm Group

Arm group label: Part 1A: Monotherapy Dose Escalation

Arm group type: Experimental

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.

Arm group label: Part 2A: Monotherapy Cohort Expansion

Arm group type: Experimental

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.

Arm group label: Part 2B: Combination Therapy Cohort Expansion

Arm group type: Experimental

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.

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

Arm group type: Experimental

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.

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

Arm group type: Experimental

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.

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov