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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03071757
Recruitment Status : Completed
First Posted : March 7, 2017
Last Update Posted : April 28, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Cancer Drug: ABBV-368 Drug: ABBV-181 Phase 1

Detailed Description:
Recruitment is closed in Part 1A; subjects are in maintenance
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 21, 2017
Actual Primary Completion Date : April 13, 2022
Actual Study Completion Date : April 13, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1A: Monotherapy Dose Escalation
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.
 Drug: ABBV-368
Intravenous infusion
Experimental: Part 2A: Monotherapy Cohort Expansion
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.
 Drug: ABBV-368
Intravenous infusion
Experimental: Part 2B: Combination Therapy Cohort Expansion
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.
 Drug: ABBV-368
Intravenous infusion

Drug: ABBV-181
Intravenous infusion
Experimental: Part 3A: 18F-AraG Imaging Substudy in TNBC Participants
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.
 Drug: ABBV-368
Intravenous infusion

Drug: ABBV-181
Intravenous infusion
Experimental: Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants
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.
 Drug: ABBV-368
Intravenous infusion

Drug: ABBV-181
Intravenous infusion


Outcome Measures
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Primary Outcome Measures :
  1. Terminal half-life (t1/2) 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 half-life of ABBV-368

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

  3. Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with ABBV-181 [ Time Frame: Up to 1 year ]
    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.

  4. Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 [ Time Frame: Up to 18 months ]
    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

  5. Time to Cmax (Tmax) 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 ]
    Time to Cmax of ABBV-368

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

  7. Number of Participants With Adverse Events [ 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 ]
    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.

  8. Maximum observed serum concentration (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 ]
    Maximum observed serum concentration of ABBV-368


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ 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 ]
    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

  2. Clinical benefit rate (CBR) [ 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 ]
    CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.

  3. Duration of Objective Response (DOR) [ 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 ]
    DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.

  4. Progression-Free Survival (PFS) [ 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 ]
    PFS time is defined as the time from the first dose of study drug (Day 1) to disease progression or death, whichever occurs first.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071757


Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
More Information
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03071757    
Other Study ID Numbers: M16-074
2016-004205-14 ( EudraCT Number )
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Solid Tumors
Cancer
Metastatic Solid Tumors
Advanced Solid Tumors
Triple negative breast cancer (TNBC)
Ovarian cancer
Hepatocellular carcinoma (HCC)
Gastric cancer
 Mesothelioma
Small cell lung cancer (SCLC)
Cholangiocarcinoma
Merkel cell carcinoma
Melanoma
Non-small cell lung cancer (NSCLC)
2'-Deoxy-2'-[18F]Fluoro-9-β-DArabinofuranosylguanine (18F-AraG)
Additional relevant MeSH terms:
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Neoplasms