A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 1b, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Subjects With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

The main objective of this study is to assess safety, tolerability, and pharmacokinetics (PK) of ABBV-368 plus tilsotolimod; ABBV-368 plus tilsotolimod and nab-paclitaxel; and ABBV-368 plus tilsotolimod, nab-paclitaxel, and ABBV-181 in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-368; Drug: Tilsotolimod; Drug: Nab-paclitaxel; Drug: ABBV-181

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06189
      • Centre Antoine Lacassagne - Nice /ID# 215706
  • Bouches-du-Rhone
    • Marseille CEDEX 05, Bouches-du-Rhone, France, 13385
      • AP-HM - Hopital de la Timone /ID# 215657
  • Gironde
    • Bordeaux, Gironde, France, 33075
      • Hopital Saint-Andre /ID# 215702
  • Ile-de-France
    • Paris CEDEX 05, Ile-de-France, France, 75248
      • Institut Curie /ID# 215653
• Germany
  • Berlin, Germany, 12203
    • Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 214197
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitaetsklinikum Erlangen /ID# 214196
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitaetsklinikum Leipzig /ID# 214200
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 215231
  • Jerusalem, Israel, 91120
    • Gastroenterology Institute, Division of Medicine /ID# 215862
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 215229
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066 CX
      • Antoni van Leeuwenhoek /ID# 215291
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 214264
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 214198
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 214110
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria /ID# 214109
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 221401
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia (ICO) L'Hospitalet /ID# 221402
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada /ID# 214263
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • The University of Chicago Medical Center /ID# 217196
  • Kentucky
    • Louisville, Kentucky, United States, 40241-2832
      • Norton Cancer Institute /ID# 216179
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer In /ID# 214050
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital /ID# 215786
  • New Jersey
    • Morristown, New Jersey, United States, 07960-6136
      • Atlantic Health System /ID# 216159
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center /ID# 215882
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0021
      • Vanderbilt Ingram Cancer Center /ID# 214040
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center /ID# 214041

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants should weigh at least 35 kg.
• Eastern Cooperative Oncology Group performance status of 0 or 1 and a life expectancy of >= 3 months.
• Participant have >= 1 lesion accessible for intratumoral injection.

• Histologically or cytologically confirmed R/M HNSCC (of the following 4 subsites: oral cavity, oropharynx, larynx, and hypopharynx) who previously progressed either during or after <= 3 prior treatment regimens administered in the recurrent or metastatic setting.

  • Must have received 1 immunotherapy regimen which included a PD-(L)1 inhibitor.
  • Must have received platinum-based therapy, or be considered ineligible for platinum-based therapy by the investigator.

Exclusion Criteria:

• Uncontrolled metastases to the central nervous system (CNS).

  • Participants with brain metastases are eligible provided that evidence of clinical and radiographic stable disease for at least 4 weeks after definitive therapy is given and participants have not used prohibited levels of steroids for at least 4 weeks prior to first dose of the study.
• Received prior treatment with OX40 or toll-like receptor (TLR) agonists (excluding topical agents).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: ABBV-368 + Tilsotolimod; Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.	Drug: ABBV-368; Intravenous (IV) infusion; Drug: Tilsotolimod; Intratumoral (IT) injection
Experimental: Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxel; Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.	Drug: ABBV-368; Intravenous (IV) infusion; Drug: Tilsotolimod; Intratumoral (IT) injection; Drug: Nab-paclitaxel; Intravenous (IV) infusion
Experimental: Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181; Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.	Drug: ABBV-368; Intravenous (IV) infusion; Drug: Tilsotolimod; Intratumoral (IT) injection; Drug: Nab-paclitaxel; Intravenous (IV) infusion; Drug: ABBV-181; Intravenous (IV) infusion; Other Names: Budigalimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.	Up to approximately 2 years following the first dose
Change in Vital Signs	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.	Up to approximately 2 years following the first dose
Change in Clinical Laboratory Test Results	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to approximately 2 years following the first dose
Maximum Observed Serum Concentration (Cmax) of ABBV-368	Maximum Serum Concentration (Cmax) of ABBV-368	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Serum Concentration (Tmax) of ABBV-368	Time to Maximum Serum Concentration (Tmax) of ABBV-368	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)	Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of ABBV-368	Terminal-Phase Elimination Rate Constant (β) of ABBV-368	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of ABBV-368	Terminal Half-Life (t1/2) of ABBV-368	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Maximum Plasma Concentration (Cmax) of Tilsotolimod	Maximum Observed Plasma Concentration (Cmax) of Tilsotolimod	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod	Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)	Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod	Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of Tilsotolimod	Terminal Half-Life (t1/2) of Tilsotolimod	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Maximum Observed Serum Concentration (Cmax) of ABBV-181 (Arm 3 Only)	Maximum Observed Serum Concentration (Cmax) of ABBV-181	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Serum Concentration (Tmax) of ABBV-181 (Arm 3 Only)	Time to Maximum Serum Concentration (Tmax) of ABBV-181	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt) (Arm 3 Only)	Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt)	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of ABBV-181 (Arm 3 Only)	Terminal-Phase Elimination Rate Constant (β) of ABBV-181	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of ABBV-181 (Arm 3 Only)	Terminal Half-Life (t1/2) of ABBV-181	Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is measured as the percentage of participants with a complete response (CR) or partial response (PR) as a confirmed response.	Up to approximately 2 years following the first dose
Clinical Benefit Rate (CBR)	CBR is measured as the percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD)	Up to approximately 2 years following the first dose
Time to Response (TTR)	TTR is the time from date of first study drug exposure to the first instance of a complete response (CR) or partial response (PR) as a confirmed response, whichever occurs first.	Up to approximately 2 years following the first dose
Progression Free Survival (PFS)	PFS is the time from date of first study drug exposure to disease progression or death, whichever occurs first.	Up to approximately 2 years following the first dose
Duration of Response (DOR)	DOR is the time from the participant's initial response (CR or PR as a confirmed response) to disease progression or death, whichever occurs first.	Up to approximately 2 years following the first dose

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Idera Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Actual): October 27, 2022
• Study Completion (Actual): October 27, 2022

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma; Locally Advanced Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: M19-894; 2019-003167-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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