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Completed

NCT Number: NCT03071757

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 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.

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Key information

Conditions

Advanced Solid Tumors Cancer Adenocarcinoma Adenoma Adnexal Diseases Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Neuroendocrine Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma DNA Virus Infections Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Infections Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Melanoma Mesothelioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Ovarian Diseases Ovarian Neoplasms Polyomavirus Infections Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Triple Negative Breast Neoplasms Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

AP-HM - Hopital de la Timone /ID# 165036, Marseille, Bouches-du-Rhone, France

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABBV-368

Drug

Intravenous infusion

ABBV-181

Drug

Intravenous infusion

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
Mar 7, 2017
Registry last updated
Apr 28, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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