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

Advanced Solid Tumors Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03071757
• Other study ID #: M16-074
• Secondary ID: 2016-004205-14
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2017
• Est. completion date: April 13, 2022

Study information

• Verified date: April 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: April 13, 2022
• Est. primary completion date: April 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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:

• 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.

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasms

Intervention

Drug:
• ABBV-368
Intravenous infusion
• ABBV-181
Intravenous infusion

Locations

Country	Name	City	State
France	Centre Leon Berard /ID# 165037	Lyon CEDEX 08	Rhone
France	AP-HM - Hopital de la Timone /ID# 165036	Marseille CEDEX 05	Bouches-du-Rhone
France	Institut Curie /ID# 165038	Paris CEDEX 05	Ile-de-France
France	Institut Gustave Roussy /ID# 165035	Villejuif Cedex	Val-de-Marne
Japan	National Cancer Center Hospital /ID# 214531	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 214530	Kashiwa-shi	Chiba
Puerto Rico	Pan American Center for Oncology Trials, LLC /ID# 213809	Rio Piedras
Spain	Hospital Duran i Reynals /ID# 205997	Hospitalet de Llobregat	Barcelona
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 205996	Madrid
Spain	Hospital General Universitario Gregorio Maranon /ID# 205999	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 211500	Madrid
Spain	Hospital Universitario Puerta de Hierro, Majadahonda /ID# 206973	Majadahonda	Madrid
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 208879	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Valencia /ID# 211499	Valencia
Taiwan	National Cheng Kung University Hospital /ID# 164002	Tainan
Taiwan	National Taiwan University Hospital /ID# 164000	Taipei City
Taiwan	Taipei Medical University Hospital /ID# 164001	Taipei City
United States	University of Virginia /ID# 212895	Charlottesville	Virginia
United States	University of Texas Southwestern Medical Center /ID# 201934	Dallas	Texas
United States	Virginia Cancer Specialists - Fairfax /ID# 160787	Fairfax	Virginia
United States	Greenville Hospital System /ID# 160785	Greenville	South Carolina
United States	Carolina BioOncology Institute /ID# 160786	Huntersville	North Carolina
United States	Moores Cancer Center at UC San Diego /ID# 201334	La Jolla	California
United States	Yale University /ID# 207895	New Haven	Connecticut
United States	University of California, Davis Comprehensive Cancer Center /ID# 201342	Sacramento	California
United States	South Texas Accelerated Research Therapeutics /ID# 160788	San Antonio	Texas
United States	Stanford University /ID# 206949	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  France,  Japan,  Puerto Rico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Terminal half-life (t1/2) of ABBV-368	Terminal half-life 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
Primary	Area under the serum concentration-time curve (AUC) of ABBV-368	Area under the serum concentration-time curve 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
Primary	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.	Up to 1 year
Primary	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	Up to 18 months
Primary	Time to Cmax (Tmax) of ABBV-368	Time to 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
Primary	Terminal phase elimination rate constant (ß) of ABBV-368	Terminal phase elimination rate constant 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
Primary	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.	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
Primary	Maximum observed serum concentration (Cmax) of ABBV-368	Maximum observed serum concentration 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	Objective Response Rate (ORR)	ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.	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	Clinical benefit rate (CBR)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.	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	Duration of Objective Response (DOR)	DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.	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	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.	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