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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

Phase 1
Completed
Conditions
Advanced Solid Tumors Cancer
Interventions
Drug: ABBV-368
Drug: Tilsotolimod
Drug: Nab-paclitaxel
Drug: ABBV-181
Registration Number
NCT04196283
Lead Sponsor
AbbVie
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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.
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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).

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Arm 1: ABBV-368 + TilsotolimodABBV-368Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.
Arm 1: ABBV-368 + TilsotolimodTilsotolimodParticipants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxelABBV-368Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxelTilsotolimodParticipants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxelNab-paclitaxelParticipants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181ABBV-368Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181TilsotolimodParticipants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181Nab-paclitaxelParticipants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181ABBV-181Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Primary Outcome Measures
NameTimeMethod
Time to Maximum Serum Concentration (Tmax) of ABBV-368Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Time to Maximum Serum Concentration (Tmax) of ABBV-368

Change in Clinical Laboratory Test ResultsUp to approximately 2 years following the first dose

Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.

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)

Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)

Maximum Observed Serum Concentration (Cmax) of ABBV-181 (Arm 3 Only)Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Maximum Observed Serum Concentration (Cmax) of ABBV-181

Change in Vital SignsUp to approximately 2 years following the first dose

Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.

Terminal-Phase Elimination Rate Constant (β) of ABBV-368Cycle 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 TilsotolimodCycle 1 through Cycle 3 (each cycle is approximately 28 days)

Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod

Terminal Half-Life (t1/2) of TilsotolimodCycle 1 through Cycle 3 (each cycle is approximately 28 days)

Terminal Half-Life (t1/2) of Tilsotolimod

Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt) (Arm 3 Only)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)

Terminal-Phase Elimination Rate Constant (β) of ABBV-181 (Arm 3 Only)Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Terminal-Phase Elimination Rate Constant (β) of ABBV-181

Terminal Half-Life (t1/2) of ABBV-181 (Arm 3 Only)Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Terminal Half-Life (t1/2) of ABBV-181

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)

Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)

Maximum Plasma Concentration (Cmax) of TilsotolimodCycle 1 through Cycle 3 (each cycle is approximately 28 days)

Maximum Observed Plasma Concentration (Cmax) of Tilsotolimod

Time to Maximum Plasma Concentration (Tmax) of TilsotolimodCycle 1 through Cycle 3 (each cycle is approximately 28 days)

Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod

Number of Participants with Adverse Events (AEs)Up to approximately 2 years following the first dose

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.

Maximum Observed Serum Concentration (Cmax) of ABBV-368Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Maximum Serum Concentration (Cmax) of ABBV-368

Terminal Half-Life (t1/2) of ABBV-368Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Terminal Half-Life (t1/2) of ABBV-368

Time to Maximum Serum Concentration (Tmax) of ABBV-181 (Arm 3 Only)Cycle 1 through Cycle 3 (each cycle is approximately 28 days)

Time to Maximum Serum Concentration (Tmax) of ABBV-181

Secondary Outcome Measures
NameTimeMethod
Duration of Response (DOR)Up to approximately 2 years following the first dose

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.

Objective Response Rate (ORR)Up to approximately 2 years following the first dose

ORR is measured as the percentage of participants with a complete response (CR) or partial response (PR) as a confirmed response.

Time to Response (TTR)Up to approximately 2 years following the first dose

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.

Clinical Benefit Rate (CBR)Up to approximately 2 years following the first dose

CBR is measured as the percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD)

Progression Free Survival (PFS)Up to approximately 2 years following the first dose

PFS is the time from date of first study drug exposure to disease progression or death, whichever occurs first.

Trial Locations

Locations (26)

The University of Chicago Medical Center /ID# 217196

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Chicago, Illinois, United States

MD Anderson Cancer Center /ID# 214041

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Houston, Texas, United States

Norton Cancer Institute /ID# 216179

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Louisville, Kentucky, United States

Barbara Ann Karmanos Cancer In /ID# 214050

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Detroit, Michigan, United States

Atlantic Health System /ID# 216159

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Morristown, New Jersey, United States

Hospital Universitario Virgen de la Victoria /ID# 214109

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Malaga, Spain

Universitaetsklinikum Erlangen /ID# 214196

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Erlangen, Bayern, Germany

Hospital Universitario de Fuenlabrada /ID# 214263

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Fuenlabrada, Madrid, Spain

The Chaim Sheba Medical Center /ID# 215229

🇮🇱

Ramat Gan, Tel-Aviv, Israel

Hopital Saint-Andre /ID# 215702

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Bordeaux, Gironde, France

Rambam Health Care Campus /ID# 215231

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Haifa, Israel

Universitaetsklinikum Leipzig /ID# 214200

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Leipzig, Sachsen, Germany

Hospital Clinico Universitario de Valencia /ID# 221401

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Valencia, Spain

Gastroenterology Institute, Division of Medicine /ID# 215862

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Jerusalem, Israel

Nebraska Methodist Hospital /ID# 215786

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Omaha, Nebraska, United States

Vanderbilt Ingram Cancer Center /ID# 214040

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Nashville, Tennessee, United States

Centre Antoine Lacassagne - Nice /ID# 215706

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Nice, Alpes-Maritimes, France

AP-HM - Hopital de la Timone /ID# 215657

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Marseille CEDEX 05, Bouches-du-Rhone, France

Institut Curie /ID# 215653

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Paris CEDEX 05, Ile-de-France, France

Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 214197

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Berlin, Germany

Hospital Universitario 12 de Octubre /ID# 214198

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Madrid, Spain

Antoni van Leeuwenhoek /ID# 215291

🇳🇱

Amsterdam, Noord-Holland, Netherlands

Instituto Catalan de Oncologia (ICO) L'Hospitalet /ID# 221402

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Hospitalet de Llobregat, Barcelona, Spain

Hospital Clinic de Barcelona /ID# 214264

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Barcelona, Spain

Hospital Universitario HM Sanchinarro /ID# 214110

🇪🇸

Madrid, Spain

Roswell Park Comprehensive Cancer Center /ID# 215882

🇺🇸

Buffalo, New York, United States

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